Dissertations / Theses on the topic 'Psychotic depression'

One hundred and twenty five patients with mild or moderate dementia according to the CAMDEX criteria, who were in contact with either a memory clinic or psychiatric services were assessed. Dementia was diagnosed according to the NINCDS ADRDA criteria, the Hachinski scale, DSMIIIR criteria, HAS AGECAT and the McKeith criteria for Senile Dementia of Lewy Body Type. Depression was diagnosed according to the DSMIIIR and RDC criteria and psychotic symptoms were assessed using the Bums Symptom Checklist. Cognitive impairment was evaluated using the CAMCOG schedule. Informants were interviewed at monthly intervals for one year concerning the symptoms of depression and psychotic symptoms experienced by the dementia sufferers. A repeat CAMCOG was undertaken one year after the initial assessment. The one month prevalence rates of delusions, visual hallucinations and delusional misidentification were 48.4%, 35.5% and 29.0% respectively. Each had a distinct pattern of associations, an impression supported by a principal components analysis which generated four psychotic factors, the three categories already discussed and comfort phenomena. Only sixteen patients had any insight into their psychotic symptoms and 61% were distressed by them. The annual incidence rate of psychotic symptoms was 46.7% and 53% of patients experienced symptom resolution. The number of months during which psychotic symptoms were experienced was significantly associated with the magnitude of cognitive deterioration. The one month prevalence rate of RDC major depression was 27.4%. An additional 27.4% of patients fulfilled the criteria for RDC minor depression. Having Alzheimer's disease was significantly inversely associated with both RDC major depression and DSMIIIR major depression. There were six patients with RDC depression in the context of vascular dementia, all of whom experienced depression for at least three months compared to only 33.3% of the patients with Alzheimer's disease. The annual incidence rate of RDC major depression was 10.6%.

Introdução: A Depressão Psicótica (DP) afeta cerca de 15-20% dos pacientes com diagnóstico de depressão. Esta condição está ligada a maior cronicidade, maior incidência de tentativas de suicídio e maior frequência de internação hospitalar em relação à Depressão Não-Psicótica. No entanto, evidências recentes sugerem que a incidência de características psicóticas pode não estar relacionada à intensidade dos sintomas depressivos. O curso distinto de doença, associado a pior resposta ao tratamento e a pior prognóstico suscitam a discussão de que a depressão psicótica pode ser uma entidade clínica distinta da depressão, representando um ponto em um continuum que tem em um de seus extremos os transtornos psicóticos e no outro, os transtornos de humor. Objetivos: Avaliar se a presença de sintomas psicóticos em pacientes internados por episódio depressivo se correlaciona com a intensidade de sintomas depressivos. Avaliar se há diferenças clínicas e funcionais que podem se relacionar com os sintomas psicóticos dos pacientes da amostra. Observar a melhora de sintomatologia psiquiátrica ao longo da internação, e se há diferença na variação de sintomas, ao longo da internação, entre os pacientes psicóticos e não-psicóticos. Métodos: 288 pacientes internados por episódio depressivo em uma unidade psiquiátrica de um hospital geral universitário foram avaliados na admissão e na alta hospitalar. Foi realizada entrevista semi-estruturada com o MINI para avaliação diagnóstica. Nos dois momentos de avaliação foram aplicadas a Escala de Hamilton para Avaliação de Depressão (HAM-D), a Escala Breve de Avaliação Psiquiátrica (BPRS), a avaliação da Impressão Clínica Global (CGI) e a Escala Global de Avaliação do Funcionamento (GAF). Outros parâmetros clínicos e epidemiológicos também foram avaliados: idade de início de sintomas, quantidade de internações prévias, tentativas de suicídio prévias, tempo de duração da internação atual e realização de Eletroconvulsoterapia (ECT) durante a internação. Resultados: 131 pacientes (45,4%) apresentaram sintomas psicóticos. Após ajuste para controle de variáveis que tinham potencial de viés de confusão – história prévia de mania ou hipomania, história prévia de uso de substâncias, sexo, idade, e anos de estudo – os dois grupos tiveram resultados similares nos resultados da HAM-D, tanto na admissão quanto na alta. Em relação às outras medidas, no entanto, os pacientes com depressão psicótica apresentaram piores níveis de funcionamento (GAF), piores resultados na avaliação clínica (CGI) e escores mais elevados na BPRS, na admissão e na alta hospitalar. Conclusão: Os pacientes com depressão psicótica apresentaram história mais grave de sintomas psiquiátricos e maior prejuízo funcional. No entanto, as diferenças entre os pacientes psicóticos e não-psicóticos não tiveram relação com os sintomas depressivos dos pacientes. Tais achados vão ao encontro de evidências recentes que sugerem que a depressão psicótica pode ser um transtorno distinto da depressão maior.
Introduction: Psychotic Depression (DP) is a medical condition that affects a significant portion of depressive patients, 15-20%. This disorder is linked to greater cronicity, higher incidence of suicide attempts and a higher frequency of hospitalization, when compared to depressive episodes without psychotic features. Nevertheless, recent evidences suggest that the presence of psychotic symptoms may not correlate to depressive symptoms severity. The discrete clinical course, along with worse response to usual treatment and worse prognosis draw a hypothesis that Psychotic Depression might be a distinct disorder in relation to major depression. It reflects the intersection of psychotic and affective dimensions, and may be placed in a point of a continuum between psychotic and affective disorders. Objectives: To evaluate if the presence of psychotic symptoms in hospitalized depressive patients correlates to depressive symptoms intensity. To evaluate the existence of clinical and functioning differences among psychotic and non-psychotic depressive inpatients that could be related to the psychotic features. To estimate clinical improvement during hospitalization, and if there are dissimilarities in the variation of symptoms between psychotic and non-psychotic depressive individuals. Methods: 288 depressive inpatients of a psychiatric ward of a university tertiary hospital were assessed at admission and at discharge. We conducted MINI semi-structured interview to determine patient diagnosis. At both assessments we applied the Hamilton Depression Rating Scale (HAM-D), the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Other clinical and epidemiological parameters were also assessed: age at onset, number of previous hospitalizations, previous suicide attempts, length of stay and Electroconvulsive therapy (ECT) in current hospitalization. Results: 131 patients (45,4%) had psychotic features. After adjusting for potential confounding variables – previous presence of mania or hypomania, history of substance use, gender, age and years of study –, both psychotic and non-psychotic depressive patients presented similar HAM-D scores at admission and at discharge. However, psychotic depressive inpatients showed worse functioning levels (GAF), worse clinical status (CGI) and higher BPRS scores, both at admission and at discharge. Conclusion: Psychotic depressive inpatients presented more severe history of psychiatric symptoms and greater functioning disability. The differences between both groups of patients did not correlate to depressive symptoms. These findings are in conformity with recent evidences that suggest that psychotic depression might be a distinct disorder in relation to major depression.

Bakgrund: Fysisk aktivitet har i studier kopplats till lindring av psykiska symtom som depression, oro, ångest samt en ökning av självupplevd livskvalitet. Vid insjuknande i psykossjukdom är det vanligt att drabbas av just ångest och depression. Dessa symtom i kombination med biverkningar från läkemedel ökar risken för en mindre hälsosam livsstil och fysisk inaktivitet, vilket kan leda till en ond cirkel och allt sämre fysisk och psykisk hälsa.Syfte: Syftet med föreliggande studie var att undersöka om det finns några skillnader mellan fysiskt hög- och lågaktiva personer med psykossjukdom avseende livskvalitet samt förekomst av depression och ångest. Syftet med studien var även att undersöka hur deltagarnas motionsvanor ser ut när det befinner sig på en sluten psykiatrisk vårdavdelning.Metod: Föreliggande studie är en kvantitativ tvärsnittsstudie. En enkät bestående av demografiska frågor, två skalor om fysisk aktivitet, en fråga om motionsform, en ångest- och depressionsskala samt en skala om livskvalitet, delades ut. I studien ingick 19 deltagare och svarsfrekvensen var 86 %. Data analyserades med det icke-parametriska testet Mann Whitney U-test. Signifikansnivån för samtliga statistiska test sattes till .05.Resultat: I analyser med skattningsskalan som mätte aktivitetsnivå överlag sågs signifikanta skillnader mellan låg- och högaktiva beträffande livskvalitet, ångest och depression (p=0.012, p=0.046, p=0.048). I analyser med skalan som mätte fysisk aktivitet de senaste två veckorna sågs inga signifikanta skillnader.Slutsatser: Personer med psykossjukdom som är högaktiva skattar sin livskvalitet högre än de som inte är det, och de skattar också lägre avseende förekomst av symtom på depression och ångest.
Background: Physical activity affects the hormonal system by alleviating psychological symptoms. There is support that physical activity also has effect on the self-perceived quality of life. Depression and anxiety are common among people with psychotic disorder, and combined with side effects from medication the risk of a less healthy lifestyle and inactivity increases.Aim: The aim of this study was to investigate whether there are any differences between those who are more and those who are less physically active when it comes to quality of life, depressive symptoms and anxiety symptoms among people with psychosis in a Swedish hospital. The aim was also to investigate what the patients’ exercise habits looked like while being admitted to the psychiatric inpatient care.Methods: This study is a quantitative cross-sectional survey performed in a psychiatric ward, specializing in psychosis. The study included 19 participants and the response rate was 86%. Data were analyzed using a non-parametric test, Mann Whitney U test. The significance levels for all statistical tests were set to .05.Results: On the scale measuring physical activity level in general there were significant differences between low-and high-level physically active participants regarding quality of life, anxiety and depression (p=0.012, p=0.046, p=0.048). On the scale, that measured the level of physical activity in the last two weeks, there were no significant differences.Conclusions: People with psychotic disorders that are high-level physically active, rate their quality of life higher and their symptom levels lower than those who score in the low-level regarding physical activity.

There is very little research on the psychosocial risk factors associated with psychotic major depression (PMD) and schizoaffective disorder, depressed type (SAD). Although there is much more research on the course and outcomes of these disorders, the studies have significant methodological limitations. Therefore, this thesis aimed to investigate the following while improving on the limitations of previous research: 1) the risk factors associated with PMD and SAD with a focus on psychosocial risk factors; and 2) the long-term course of illness and outcomes in cases with PMD and SAD. A case control study of incident psychosis cases was used to examine psychosocial risk factors in PMD and SAD cases compared with schizophrenia and bipolar disorder cases. A cohort study following up all cases identified in the case control study was conducted to investigate course of illness and outcomes. Findings on the risk factors suggest that less psychosocial risk factors are involved in the aetiology of PMD and SAD compared with schizophrenia and bipolar disorder. Exploratory analyses of life events indicate that humiliation life events could be an important factor in the development of PMD and requires further research. Findings on outcomes suggest that PMD cases are more likely to self-harm and attempt suicide but are less likely to use inpatient services and have a lower proportion of compulsory admissions. These findings have important clinical implications. Findings on risk factors and outcomes in SAD cases are similar but a lack of power due to low numbers limits the interpretation of the findings. Important differences in both the risk factors and outcomes analyses were identified when based on the baseline and lifetime diagnoses. This highlights the importance of accounting for diagnostic change when examining these diagnostic groups.

Background: It is commonly assumed that there are clear lines of demarcation between anxiety and depressive disorders on the one hand and psychosis on the other. Recent evidence, however, suggests that this principle may be in need of updating. Methods: Depressive and/or anxiety disorders, with no previous history of psychotic disorder, were examined for the presence of psychotic symptoms in a representative community sample of adolescents and young adults (Early Developmental Stages of Psychopathology study; n=3021). Associations and consequences of psychotic symptomatology in the course of these disorders were examined in terms of demographic distribution, illness severity, onset of service use, and risk factors. Results: Around 27% of those with disorders of anxiety and depression displayed one or more psychotic symptoms, vs 14% in those without these disorders (OR 2.23, 95% CI 1.89–2.66, P < .001). Presence as compared with nonpresence of psychotic symptomatology was associated with younger age (P < .0001), male sex (P < .0058), and poorer illness course (P < .0002). In addition, there was greater persistence of schizotypal (P < .0001) and negative symptoms (P < .0170), more observable illness behavior (P < .0001), greater likelihood of service use (P < .0069), as well as more evidence of familial liability for mental illness (P < .0100), exposure to trauma (P < .0150), recent and more distant life events (P < .0006–.0244), cannabis use (P < .0009), and any drug use (P < .0008). Conclusion: Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.

Background: It is commonly assumed that there are clear lines of demarcation between anxiety and depressive disorders on the one hand and psychosis on the other. Recent evidence, however, suggests that this principle may be in need of updating. Methods: Depressive and/or anxiety disorders, with no previous history of psychotic disorder, were examined for the presence of psychotic symptoms in a representative community sample of adolescents and young adults (Early Developmental Stages of Psychopathology study; n=3021). Associations and consequences of psychotic symptomatology in the course of these disorders were examined in terms of demographic distribution, illness severity, onset of service use, and risk factors. Results: Around 27% of those with disorders of anxiety and depression displayed one or more psychotic symptoms, vs 14% in those without these disorders (OR 2.23, 95% CI 1.89–2.66, P < .001). Presence as compared with nonpresence of psychotic symptomatology was associated with younger age (P < .0001), male sex (P < .0058), and poorer illness course (P < .0002). In addition, there was greater persistence of schizotypal (P < .0001) and negative symptoms (P < .0170), more observable illness behavior (P < .0001), greater likelihood of service use (P < .0069), as well as more evidence of familial liability for mental illness (P < .0100), exposure to trauma (P < .0150), recent and more distant life events (P < .0006–.0244), cannabis use (P < .0009), and any drug use (P < .0008). Conclusion: Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.

UVOD: Moždani udar spada u grupu masovnih nezaraznih bolesti, koje se smatraju najčešćim oboljenjima savremenog čoveka. On predstavlja jedan od najčešćih uzroka mortaliteta i invaliditeta u savremenom svetu. Među brojnim pratećim komplikacijama moždanog udara, navode se psihički poremećaji: depresija, anksioznost i psihotični poremećaji. Utvrđivanje povezanosti moždanog udara sa psihičkim poremećajima, kao i mehanizma njihovog nastanka predstavlja značajan doprinos boljem razumevanju ovog veoma čestog oboljenja, a njihov rani tretman omogućio bi brži i potpuniji oporavak nakon moždanog udara. CILJ: Utvrditi karakteristike psihičkog funkcionisanja osoba nakon ishemičnog moždanog udara, utvrditi uticaj lokalizacije lezije na nastanak određenih psihičkih poremećaja nakon moždanog udara, utvrditi uticaj vaskularnog statusa na nastanak psihičkih poremećaja, te utvrditi korelaciju između psihičkih komplikacija moždanog udara i brzine i stepena oporavka opšte životne aktivnosti. MATERIJAL I METODE: Istraživanje je izvedeno kao prospektivna studija, obuhvatilo je 101 pacijenta oba pola obolelih od moždanog udara, koji su hospitalno lečeni na Klinici za neurologiju u Novom Sadu. Svim pacijentima je uzeta anamneza o toku bolesti, faktorima rizika za moždani udar, kao i laboratorijska dijagnostika. Svim pacijentima načinjena je kompjuterizovana tomografija (CT) mozga (ili magnetna rezonanca - MRI mozga), ultrazvučni pregled karotidnih arterija, vertebrobazilarnih i krvnih sudova Willisovog poligona. Stepen neurološkog deficita i praćenje funkcionalnog oporavka u akutnoj fazi i nakon 3 meseca vršeno je primenom Skale Moždanog Udara Nacionalnog Instituta za Zdravlje (NIHSS), Rankinove skale i Bartelovog indeksa. Svim pacijentima je načinjena eksploracija psihičkog statusa u akutnoj fazi bolesti primenom Bekove Skale Depresije 2 (BDI-2), Skale procene anksioznosti kao stanja i odlike (STAI), Skale pozitivnih i negativnih sindroma (PANSS) i Kornelovog regrutnog indeksa (CSI). Kontrolno testiranje gore navedenim testovima obavljeno je nakon 3 meseca. Od statističkih metoda korišćena je deskriptivna statistika: tabelarni prikazi učestalosti i procentualna izraženost kod neparametrijski (nominalno ili ordinarno) organizovanih varijabli. Za ukršten prikaz dve varijable korišćene su tabele kontingencije. Takođe su korišćene mere centralne tendencije (aritmetička sredina) i mere disperzije (standardna devijacija) kod parametrijski korektno uređenih varijabli. Pored toga, korišćen je Hi-kvadrat test za utvrđivanje razlika između grupa za varijable nominalnog nivoa merenja, Kramerovo V za utvrđivanje povezanosti između nominalnog nivoa merenja, Pirsonov koeficijent korelacije r, za utvrđivanje povezanosti između varijabli intervalnog nivoa merenja, te analiza varijanse (ANOVA) za utvrđivanje značajnosti razlika između aritmetičkih sredina više grupa. REZULTATI: U ispitivanje je uključen 101 pacijent, 65.3% muškog pola, 34.7% ženskog pola. Prosečna starost bila je 60.69 godina (medijana=62.00, standardna devijacija =10.828, statistička greška=1.077). 38.6% je imalo lokalizaciju u desnoj hemisferi velikog mozga, 34.7% u levoj hemisferi, 4% u cerebelumu, 11.9% u moždanom stablu, dok je 10.9% imalo višestruku lokalizaciju infarkta. 39.6% je imalo teritorijalni infarkt, a 59.4% lakunarni infarkt. Distribucija faktora rizika za moždani udar bila je uobičajena za podneblje na kojem je vršeno istraživanje. 26.7% je imalo uredan nalaz na karotidnim krvnim sudovima, 26.7% je imalo difuznu ateromatozu, 27.7% je imalo stenozu ACI <70% , dok je 18.8% pacijenata imalo stenozu ACI>70%. U odnosu na nalaz u VB slivu, 52.5% je imalo uredan nalaz, a 47.5% patološki nalaz (stenozu i difuznu ateromatozu). 54.5% pacijenata je imalo uredan nalaz na arterijama Willisovog poligona, a 45.5% je imalo patološki nalaz (stenozu i difuznu ateromatozu). 5.9% je imalo depresivni poremećaj, 29.7% anksiozni poremećaj, 9.9% neurotski poremećaj i 2% psihotični poremećaj. U odnosu na pol, depresivni poremećaj javlja kod 3% muškaraca i 11.4% žena, anksiozni kod 25.8% muškaraca i 37.1% žena, neurotski kod 7.6% muškaraca i 14.3% žena i psihotični kod 3% muškaraca, dok kod žena nije zabeležen. U odnosu na životno doba, kod mlađih od 45 godina depresija nije bila prisutna, anksioznih je bilo 30%, 10% psihotičnih, dok neurotičnih nije bilo. U grupi 46-65 godina depresivnih je bilo 6.9%, anksioznih 22.4%, neurotičnih 12.1%, a psihotičnih 1.7%. U grupi starijih od 65 godina, depresivnih je bilo 6.1%, anksioznih 42.4%, neurotičnih 9.1%, dok psihotičnih nije bilo. Distribucija odgfovora dobijenih na BDI-2 skali ukazivala je na veću učestalost depresivnog poremećaja kod lezija u levoj hemisferi velikog mozga. Distribucija odgovora dobijenih primenom STAI ukazivala je na veću učestalost anksioznog poremećaja kod lezija desne hemisfere. Distribucija odgovora dobijenih primenom CSI ukazivala je na veću učestalost neurotskog poremećaja kod višestrukih lezija. Distribucija odgovora dobijenih primenom PANSS ukazivala je na veću učestalost psihotičnog poremećaja kod lezija desne hemisfere. Upoređivanje lezije na karotidama i psihičkih poremećaja pokazalo je na progresivni porast učestalosti psihičkih poremećaja sa težinom lezije na karotidnim krvnim sudovima, kao i na potpuno odsustvo psihičkih poremećaja kod osoba koje su imale uredan nalaz na karotidama. Praćenje uticaja psihičkih poremećaja (sumarno i pojedinačno) na funkcionalni oporavak pacijenata nakon moždanog udara, nije pokazalo statistički značajan uticaj. Zabeleženo je statistički značajno udruženo pojavljivanje depresivnog i anksioznog, depresivnog i neurotskog i anksioznog i neurotskog poremećaja, bez značajne interakcije navedenih poremećaja sa psihotičnim poremećajem. ZAKLJUČAK: Kod pacijenata sa ishemičnim moždanim udarom najveća je učestalost anksioznog poremećaja, zatim depresivnog poremećaja, a najređe se javlja psihotični poremećaj. Depresivni i anksiozni poremećaj značajno su češći kod žena, dok se psihotični poremećaji isključivo javljaju kod muškaraca. Depresivni poremećaj značajno se češće javlja u srednjem i starijem životnom dobu, anksiozni poremećaj se češće javlja u mlađem i srednjem životnom dobu, dok se psihotične manifestacije javljaju najčešće u srednjem životom dobu. Depresivni i anksiozni poremećaj jednako se često javljaju kod pacijenata sa teritorijalnim i lakunarnim infarktom, dok se psihotične manifestacije isključivo javljaju kod pacijenata sa teritorijalnim infarktom. Ne postoji značajna korelacija između prisustva faktora rizika za moždani udar i pojave psihičkih poremećaja, iako je upadljivo odsustvo psihičkih poremećaja kod pacijenata bez faktora rizika za moždani udar. Nakon 3 meseca od moždanog udara nije primećena značajnija regresija simptoma psihičkih poremećaja. Anksiozni poremećaj i psihotične manifestacije se statistički značajno češće javljaju kod infarkta u desnoj hemisferi, dok za depresivni poremećaj nije potvrđeno statistički značajno češće pojavljivanje kod infarkta u levoj hemisferi. Psihički poremećaji kod pacijenata sa moždanim udarom češće se javljaju kod pacijenata sa lezijama u karotidnom slivu, što se povećava sa težinom lezije i veličinom stenoze. Ne postoji statistički značajna korelacija između lezija krvnih sudova u vertebrobazilarnom slivu i Willisovom poligonu sa pojavom psihičkih poremećaja. Nije dokazan značajan uticaj psihičkih poremećaja na oporavak bolesnika nakon moždanog udara. Dokazan je visok stepen udruženog javljanja depresivnog i anksioznog poremećaja.
INTRODUCTION: Stroke belongs to noninfectious diseases, which are considered the most common diseases of modern man. It is one of the most common causes of mortality and disability in the modern world. The many associated complications of stroke include mental disorders: depression, anxiety and psychotic disorders. Determining the relationship between stroke and mental disorders, as well as enlightening their underlying mechanism, represents a significant contribution to a better understanding of this very frequent disease, and an early treatment of these associated disorders should allow a faster and more complete recovery from stroke. OBJECTIVE: To determine characteristics of mental functioning after ischemic stroke, to determine the impact of lesion localization on development of certain mental disorders after stroke, to determine the impact of vascular status on development of mental disorders, and to determine the correlation between the associated mental disorders and the speed and degree of recovery of general life activities. MATERIALS AND METHODS: The research was conducted as a prospective study that included 101 ischemic stroke patients of both sexes, hospitalized at the Clinic of Neurology in Novi Sad. Data about the course of disease and stroke risk factors was collected and laboratory diagnostics was performed in all patients. All patients underwent brain computed tomography (CT) (or magnetic resonance imaging - MRI), and ultrasound examination of carotid and vertebrobasilar arteries and the circle of Willis. The degree of neurological deficit and functional recovery in the acute phase and at 3-month follow-up were assessed using the National Institute of Health Stroke Severity (NIHSS) scale, the Rankin scale, and the Barthel Index. All patients underwent psychological exploration of the mental status in the acute phase of stroke by using the Beck Depression Inventory 2 (BDI - 2), the State-Trait Anxiety Inventory (STAI), the Positive and Negative Syndrome Scale (PANSS), and the Cornell Services Index (CSI). Follow-up testing with the same tests was performed after 3 months. Statistical analysis included methods of descriptive statistics: tabular presentation of the frequency and percentages in case of nonparametric (nominal or ordinal) variables. Contingency tables were used to present relationships between two variables. In addition, measures of central tendency (arithmetic mean) and measures of dispersion (standard deviation) were used for parametric variables. The chisquared test was used to determine differences between groups for nominal measurement variables, Cramer’s V was used to examine association between nominal levels of measurement. Association between interval measurement variables was measured by the Pearson correlation coefficient (r), and significance of differences between arithmetic means of more groups was determined by the analysis of variance (ANOVA). RESULTS: The study included 101 patients, 65.3% male and 34.7% female. The average age of patients was 60.69 years (median=62.00, standard deviation=10.828, statistical error=1.077). Stroke localizations were as follows: the right cerebral hemisphere in 38.6%, the left hemisphere in 34.7%, the cerebellum in 4%, the brainstem in 11.9%, and 10.9% of patients had multiple localizations. In 39.6% of patients, stroke was territorial, and in 59.4% lacunar. The distribution of risk factors for stroke was typical for the study area. Normal carotid arteries were found in 26.7%, 26.7% had diffuse atheromatosis, 27.7% had <70% ACI stenosis, and 18.8% had >70% ACI stenosis. As regards VB circulation, 52.5% had normal findings and 47.5% had pathological findings (stenosis and diffuse atheromatosis). As regards the circle of Willis, 54.5% had normal findings and 45.5% had pathological findings (stenosis and diffuse atheromatosis). Regarding mental functioning, 5.9% had depressive disorder, 29.7% had anxiety disorder, 9.9% had neurotic disorder, and 2% had psychotic disorder. In relation to sex, mental disorders were present as follows: depressive disorder in 3% of men and 11.4% of women, anxiety disorder in 25.8% of men and 37.1% of women, neurotic disorder in 7.6% of men and 14.3% of women, and psychotic disorder in 3% of men and none of women. With respect to age, among patients under 45 years of, age none had depressive disorder, 30% had anxiety disorder, 10% had psychotic disorder, and none had neurotic disorder. In the group of patients aged 46-65 years, 6.9% had depressive disorder, 22.4% had anxiety disorder, 12.1% had neurotic disorder, and 1.7% had neurotic disorder. In the group above 65 years of age, 6.1% had depressive disorder, 42.4% had anxiety disorder, 9.1% had neurotic disorder, and none had psychotic disorder. The distribution of responses obtained on the BDI-2 showed a higher prevalence of depressive disorder in patients with lesions in the left cerebral hemisphere. The distribution of responses obtained on the STAI showed a higher prevalence of anxiety disorder in patients who had lesion of the right hemisphere. The distribution of responses obtained on the CSI showed a higher prevalence of neurotic disorder in those who had multiple lesions. The distribution of responses obtained by the PANSS indicated a higher prevalence of psychotic disorder in those with lesion of the right hemisphere. Comparison of carotid artery lesions and mental disorders showed a progressive increase in the prevalence of mental disorders with increasing severity of the lesions, as well as a complete absence of mental disorders in people who had normal findings on carotids. The follow-up results showed that mental disorders (generally and individually) did not have a statistically significant effect on functional recovery of stroke patients. There were statistically significant comorbidities of depressive disorder and anxiety disorder, depressive disorder and neurotic disorder, and anxiety disorder and neurotic disorder, and no significant interactions of any of these disorders with psychotic disorder. CONCLUSION: In patients with ischemic stroke, anxiety disorder has the highest prevalence, followed by depressive disorder, whereas psychosis is the rarest. Depressive and anxiety disorders are significantly more common in women, while psychotic disorder occurs exclusively in men. Depressive disorder is significantly more common in the middle and old ages, anxiety disorder is more frequent in the younger and middle ages, while psychotic manifestations occur most often in the middle age of life. Depressive and anxiety disorders are similarly prevalent in patients with territorial and lacunar strokes, while psychotic manifestations occur exclusively in patients with territorial stroke. There is no significant correlation between the presence of stroke risk factors and mental disorders, although there is an evident absence of mental disorders in patients without stroke risk factors. Three months after stroke, no significant regression of the symptoms of mental disorders was observed. Anxiety disorder and psychotic manifestations are significantly more common in right hemispheric stroke, while as regards depressive disorder, there is no statistically significant association with left-hemispheric stroke. Mental disorders in stroke patients are more common in those with carotid lesions and increase in severity with increasing severity of lesion and degree of stenosis. There are no statistically significant correlations between lesions in the vertebrobasilar circulation or the circle of Willis and development of mental disorders. No significant impact of mental disorders on recovery from stroke was found. A high prevalence of comorbid depressive and anxiety disorders was proven/confirmed.

There has been renewed interest into affective symptoms and psychological approaches to schizophrenia and other psychosis, yet no in-depth investigation as to the course, consequences or indeed psychological causes of depression in a phase specific manner in the important first episode. Our understanding of risk and aetiological processes in psychotic illness will only advance once we accurately identify the “end phenotype” of psychotic illness. This series of studies investigates the course of depression in first episode psychosis, its significance in terms of suicidal thinking, and relation to both diagnosis and other symptom domains. Depression in the acute and post psychotic phases is explored, through the importance of the awareness and appraisal of positive symptoms, and diagnosis itself. Significant findings include a pervasive nature of depression throughout the course of first episode psychosis, the predictive nature of prodromal depression and the high prevalence of suicidal acts. Appeasement and engagement with voices, subordination to persecutors and the (ineffective) use of safety behaviours drive a position of entrapment, demoralization and a lack of control. In addition negative illness appraisals are stable and may vary between cultural groups. Implications are explored, in terms of clinical practice, aetiological pathways, potential treatments and intervention strategies

A epilepsia é um transtorno do funcionamento cerebral caracterizado por crises epilépticas recorrentes que acomete cerca de 1 a 2% da população mundial. A epilepsia do lobo temporal (ELT) é o subtipo mais prevalente. A refratariedade aos medicamentos é comum e cerca de 40 % destes pacientes apresentam transtornos psiquiátricos. Neste trabalho utilizamos o método de TacMan real time PCR para quantificar o mRNA de subtipos dos receptores de noradrenalina, dopamina, serotonina e substância P em hipocampos cirurgicamente removidos de pacientes com ELT para conhecer o papel destes na ELT com ou sem comorbidade psiquiátrica (depressão ou psicose). Nossa amostra foi de 48 pacientes com ELT sem (Epilepsia - 24) ou com comorbidade psicótica (Psicose - 10) ou depressiva (Depressão - 14) e 8 Controles (necrópsias). O receptor adrenérgico-α2A (AD2A) apresentou diferença entre os grupos (p = 0,0059) com significância para a variável Antiepiléptico (p = 0,0374) e pós-teste significante de maior expressão do mRNA de AD2A no grupo Epilepsia comparado com Controle e com Psicose. A ativação dos receptores α2A no hipocampo pelos antiepilépticos pode explicar nossos achados do grupo Epilepsia comparado ao Controle, corroborando a literatura acerca do AD2A na epilepsia e em relação aos antiepilépticos. O AD2C mostrou diferença entre os grupos (p = 0,0016), sem significância nas variáveis de controle e significante maior expressão do mRNA de AD2C no grupo Epilepsia comparado ao Controle e Psicose. O AD2C é encontrado em áreas que processam informações sensoriais e controlam atividades motoras e emocionais relacionadas, o que pode explicar nossos resultados. Parece ser importante na patologia relacionada à ELT e merece ser estudado. A não diferença entre Epilepsia e Depressão para AD2A e AD2C, parecem confirmar uma relação bi-direcional ou um mecanismo patogênico comum entre epilepsia e depressão, enquanto a menor expressão de AD2A e AD2C nos psicóticos parece indicar diferenças nos mecanismos adrenérgicos ligados a psicose e epilepsia. D2 mostrou diferença entre os grupos (p = 0,0125) com resultado significativo para a variável Subtipo de Diagnóstico Psiquiátrico (p = 0,0239), provavelmente devido a cronicidade da doença e a quantidade de episódios depressivos apresentados pelos sujeitos. Quanto maior a freqüência das crises (p = 0,0381) maior a expressão do D2 no grupo Epilepsia e no Depressão comparados ao Controle. Estes achados sugerem a participação deste receptor na depressão comórbida na ELT; corroboram que o monitoramento dopaminérgico límbico pode ser útil para desenvolver novos antidepressivos e propõem pesquisas futuras sobre D2 em epilépticos. A participação de 5-HT2A na ELT é indicada, pois, sua maior expressão no grupo Epilepsia em relação ao Controle foi significativa (p = 0,0273). Quanto maior a freqüência das crises epilépticas maior a expressão do 5-HT2A (p = 0, 0433). Não encontramos resultados significativos referentes aos receptores D4, 5-HT1A, 5-HT2C e NK1. Nossos resultados mostraram a possibilidade da aplicação do TacMan real time PCR no estudo de receptores de neurotransmissores, sugeriu a importância dos receptores estudados na ELT e comorbidades psiquiátricas, e que outras estruturas límbicas, como a amígdala, sejam focos de investigação.
Epilepsy is a mental functional disorder characterized by recurrent seizures that affect about 1 to 2% of world population. Temporal lobe epilepsy (TLE) is the most prevalent subtype. The refractory to medication is common and about 40% of these patients have psychiatric disorders. This study used the TacMan real time PCR method to quantify noradrenergic, dopaminergic, serotoninergic and substance P receptors subtypes mRNA expression in hippocampus surgically removed from patients with TLE to know their role in TLE with or without psychiatric commorbity (depression or psychosis). Our sample consisted of 48 TLE patients without (Epilepsy - 24) or with psychotic (Psychosis - 10) or depressive (Depression - 14) commorbity and 8 Controls (necropsies). The α2A adrenergic receptor (AD2A) showed difference between groups (p = 0.0059) with significance for Antiepileptic Medication variable (p = 0.0374) and post-hoc test significantly greater AD2A mRNA expression of Epilepsy group compared with Control and Psychosis. The activation of hippocampus α2A receptors by antiepileptic drugs can explain our findings of the Epilepsy group compared with Control, corroborating the literature about the AD2A in epilepsy and for antiepileptic drugs. The AD2C showed differences between groups (p = 0.0016) without significance in the variables of control and significantly greater AD2C mRNA expression of the Epilepsy group compared to Control and Psychosis. The AD2C is found in areas that process sensory information and control motor and emotional related activities, which may explain our results. It seems to be important in the pathology related to TLE and deserves to be studied. No differences between Epilepsy and Depression to AD2A and AD2C seem to confirm a bi-directional relation or a common pathogenic mechanism between epilepsy and depression, while the lowest AD2A and AD2C expression within psychotics seem suggests differences in adrenergic mechanisms linked to psychosis and epilepsy. D2 showed differences between groups (p = 0.0125) with significant results for the variable Subtype of Psychiatric Diagnosis (p = 0.0239), probably due to chronic disease and the number of depressive episodes presented by subjects. The higher the frequency of seizures (p = 0.0381) the higher was the D2 expression within Epilepsy group compared with Control and Depression compared to Control. These findings suggest the involvement of this receptor in TLE commorbid depression; corroborate that limbic dopaminergic monitoring may be useful in developing new antidepressants and propose future research on D2 in epileptics. The participation of 5-HT2A in TLE is indicated, therefore its significant higher expression in the Epilepsy group in relation to Control (p = 0.0273). The higher the frequency of seizures the higher was the 5-HT2A expression (p = 0.0433). We found no significant results for the D4, 5-HT1A, 5-HT2C and NK1 receptors. Our results showed the possibility of TacMan real time PCR method application in TLE neurotransmission receptors study, suggested the importance of the studied receptors in TLE and psychiatric commorbities and that other limbic structures, as the amygdala, should be investigation targets.

Background: Depressive symptoms have been found to accompany and develop following psychosis. Depression following psychosis has been associated with negative self-cognitions. Acceptance and Commitment Therapy (ACT) posits that avoidance of distressing internal experiences can lead to psychological inflexibility and the maintenance of distress. Aims: The study conducted a preliminary investigation into the effectiveness and acceptability of a brief ACT-based defusion intervention aimed at increasing psychological flexibility and reducing distress associated with negative self cognitions. This research also explored the extent to which levels of depression experienced by individuals with psychosis are associated with internal shame, psychological flexibility and emotion regulation difficulties. Method: A randomised controlled trial design was used in phase 1 of the study. Individuals were randomised to either a brief defusion intervention (N=8) or a control condition (N=8).An exploratory correlational design was used in phase 2 of the research. Sixteen participants completed questionnaires. Results: Levels of depression in individuals with psychosis were associated with internal shame, psychological inflexibility and difficulties with emotion regulation. A trend approaching significance suggested that the change in levels of distress related to a negative self cognition in the defusion group was greater than the corresponding change for the control group. Conclusions: Individuals randomised to a defusion exercise found the intervention acceptable and it appears to offer promise for reducing distress associated with negative self cognitions.

Persecutory delusions are one of the most common and distressing symptoms of psychosis. Many studies indicate an association of persecutory delusions with depression. A direct role for depression-related cognitive factors in the maintenance of persecutory delusions has not been systematically examined, despite such processes being implicated in a cognitive model. To determine whether depression in people with persecutory delusions is associated with the same cognitive factors implicated in major depressive disorder, and to examine these factors as predictors of the persistence of persecutory delusions over time. A systematic literature review formed the basis of two linked studies: one cross-sectional and one longitudinal. In the first study, 60 participants with persecutory delusions and schizophrenia spectrum diagnoses were classified into two groups, according to whether or not they met ICD-10 criteria for major depression. Assessments were made of delusions, depression and key cognitive factors from the literature: schematic beliefs, avoidance, rumination, memory specificity and problem solving. The groups’ scores were compared, and the same comparisons were made between 30 participants with non-psychotic depression and 30 non-clinical controls. For the second study, 54 participants with delusions were re¬assessed six months later, and predictors of symptom persistence were examined. 50% of participants with persecutory delusions met diagnostic criteria for major depression. With baseline paranoia levels controlled, higher baseline depression predicted higher paranoia six months later. Negative schematic beliefs about the self and problem solving deficits predicted the persistence of both paranoia and depression over time. Coexisting depression predicts the persistence of persecutory delusions, suggesting a causal association. Trials are warranted of depression-related therapeutic techniques for people with delusions, including those that target negative schematic beliefs about the self. An improved understanding of the mechanisms that maintain paranoid beliefs can enable the development of better treatments.

A depressão é um transtorno prevalente, de curso crônico e altamente incapacitante. Entretanto, os avanços na pesquisa de sua fisiopatogenia e tratamento tem sido insatisfatórios, possivelmente pelo fato de o conceito de Depressão Maior incluir diferentes patologias em uma mesma categoria diagnóstica. A identificação de subtipos específicos de depressão com características mais homogêneas entre os pacientes poderia permitir a identificação de fatores biológicos, psicossociais e de resposta a tratamento associados a cada um destes subtipos. Objetivos: Avaliar em uma amostra de pacientes brasileiros um novo modelo de classificação dos transtornos depressivos, proposto por Parker e colaboradores. Avaliar se os três subtipos propostos neste modelo (nãomelancólico, melancólico e psicótico) apresentam-se clinicamente de forma semelhante ao modelo teórico. Avaliar se os pacientes com depressão melancólica de acordo com os critérios deste modelo diferenciam-se dos nãomelancólicos em aspectos clinicamente relevantes. Métodos: Cento e oitenta e um pacientes ambulatoriais com diagnóstico de depressão maior unipolar de acordo com os critérios do DSM-IV-TR foram avaliados em um estudo transversal. Os pacientes foram avaliados em relação ao subtipo melancólico de depressão tanto pelo critério do DSM-IV-TR quanto pela escala CORE de distúrbio psicomotor, critério utilizado pelo modelo estudado neste trabalho. Foi avaliada a presença de sintomas psicóticos e intensidade dos sintomas depressivos. Os pacientes foram também avaliados em relação a comorbidades, ideação suicida, eventos estressores, qualidade de vida, cuidados parentais e personalidade. Resultados: Pacientes com depressão melancólica apresentaram maior intensidade dos sintomas depressivos e praticamente o triplo da prevalência de sintomas psicóticos. A presença de sintomas psicóticos não esteve associada à maior intensidade dos sintomas depressivos. A depressão melancólica, mostrou-se diferente da depressão não-melancólica em relação a ideação suicida, comorbidades psiquiátricas, personalidade e cuidados parentais. Conclusão: A maior prevalência de sintomas psicóticos na depressão melancólica sugere semelhanças entre esta e a depressão psicótica. A depressão melancólica mostrou diferenciar-se da não-melancólica em diversos desfechos avaliados, sugerindo ser um subtipo distinto com características próprias. Estes resultados reforçam a importância do diagnóstico de depressão melancólica e a utilidade do distúrbio psicomotor para a definição deste diagnóstico.
Depression is a prevalent, chronic and highly disabling disorder. However, current advances in research of its pathophysiology and treatment are unsatisfactory. This is likely to be consequence of the Major Depression diagnosis that includes different disorders in a unique diagnostic category. Identification of specific subtypes of depression, each of them with more homogeneous characteristics could allow to the identification of biological and psychosocial factors as well as treatment response patterns of each subtype. Objectives: To evaluate, in a Brazilian patients sample, a novel model for classifying depressive disorders, proposed by Parker and colleagues. To assess whether the three proposed subtypes (non-melancholic, melancholic and psychotic) present clinically according to the theoretical model. To assess whether patients with melancholic depression, according to this model criteria, differentiate from non-melancholic in clinically relevant aspects. Method: One hundred eighty one outpatients with Unipolar Major Depression, according to the DSM-IV-TR criteria were evaluated in a transversal study. Patients were assessed in terms of melancholic status both by the DSM-IV-TR criteria and the CORE measure of psychomotor disturbance, the criterion used in the model studied. The presence of psychotic symptoms and the severity of depressive symptoms were appraised. Patients were also assessed in terms of psychiatric comorbidities, suicidal ideation, stressful live events, quality of life, parental care and personality. Results: Patients with melancholic depression presented greater severity of depressive symptoms and almost three times the prevalence of psychotic symptoms. Melancholic depression was different from non-melancholic in terms of suicidal ideation, psychiatric comorbidities, personality and parental care. Conclusion: The greater prevalence of psychotic symptoms in those with melancholic depression suggests similarities between this and the psychotic depression. Melancholic depression differentiates from the non-melancholic subtype in a series of evaluated outcomes. This suggests it to be a distinct disorder with its own characteristics. These results reinforce the importance of the diagnosis of melancholic depression and the usefulness of psychomotor disturbance in the definition of this diagnosis.

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população em geral e estão associados à grande morbidade e elevadas taxas de comprometimento funcional, tornando-os um grave problema de saúde pública. O desenvolvimento de novos métodos de auxílio diagnóstico e prognóstico a pratica clínica psiquiátrica possibilitando que intervenções efetivas sejam feitas precocemente na história natural da doença são, dessa forma, desejáveis. A classificação de padrões neuroanatômicos é uma robusta técnica para processamento e análise de imagens médicas que permite tanto a realização de comparações voxel-a-voxel entre grupos com alta dimensionalidade de variáveis, como a classificação individualizada das imagens. OBJETIVOS: Avaliar o desempenho diagnóstico de um classificador de padrões morfológicos complexos baseado em support vector machine (SVM) na discriminação entre diferentes transtornos psicóticos no momento do primeiro episódio, utilizando-se uma abordagem epidemiológica para a seleção de casos e controles, bem como na determinação de prognóstico de 1 ano em pacientes com primeiro episódio de esquizofrenia. MÉTODOS: Uma amostra de 62 pacientes com primeiro episódio de esquizofrenia/ transtorno esquizofreniforme, 23 casos de primeiro episódio de mania psicótica (transtorno bipolar tipo I, TB-I), e 19 indivíduos com depressão maior (DM) psicótica foram estudados com ressonância magnética (RM) estrutural de 1.5T, assim como um total de 89 controles residentes na mesma região dos casos. As imagens T1 foram inicialmente registradas a uma imagem molde comum através de um método com preservação de massa, permitindo a obtenção de volumes cerebrais regionais. Um classificador neuroanatômico multivariado baseado em redução de dimensionalidade e SVM foi utilizado para identificar o melhor conjunto de características morfológicas que diferencia cada transtorno psicótico (esquizofrenia/ transtorno esquizofreniforme, TB-I e DM psicótica) de subgrupos de controles saudáveis pareados por idade, gênero e anos de escolaridade. Os resultados obtidos pelo classificador foram, então, analisados com o auxílio de uma curva ROC, e um mapa espacial de alta dimensionalidade daquelas regiões cerebrais que constituem um padrão de distribuição tecidual cerebral característico de cada transtorno psicótico em relação aos controles foi gerado. RESULTADOS: O classificador obteve uma discriminação apenas modesta entre pacientes com primeiro episódio de esquizofrenia/ transtorno esquizofreniforme e controles saudáveis, com uma medida de área sob a curva (AUC) de 0,75 e acurácia de 73,4%. O mapa espacial discriminatório resultante mostrou um padrão complexo de alterações volumétricas comprometendo regiões fronto-límbicas tanto de substância cinzenta como de substância branca cerebral bilateralmente, fascículos cerebrais associativos, terceiro ventrículo e o ventrículo lateral esquerdo. Um desempenho diagnóstico pobre foi observado nas comparações entre pacientes com TB-I e MD psicótica e controles. Além disso, o classificador baseado em SVM não conseguiu predizer satisfatoriamente o prognóstico de 1 ano (evolução de remissão versus não remissão) dos pacientes com primeiro episódio de esquizofrenia. CONCLUSÃO: Utilizando uma amostra de pacientes com psicoses afetivas e não afetivas com características clínicas semelhantes aos pacientes vistos na nossa prática psiquiátrica (comorbidade com transtornos de uso de substâncias e curso clínico variável) e selecionados através de uma abordagem epidemiológica populacional, o classificador de padrões neuroanatômicos não obteve bom desempenho diagnóstico na discriminação entre as formas esquizofreniformes e afetivas de primeiro episódio psicótico, e também não conseguiu predizer satisfatoriamente o prognóstico de 1 ano em primeiro episódio de esquizofrenia, utilizando apenas imagens estruturais de RM
INTRODUCTION: Psychotic disorders are prevalent medical conditions in the general population, and are usually associated with high morbidity and functional impairment rates, which make them a major concern for public health. The development of new methods aiming to aid diagnostic and prognostic value in clinical psychiatric practice thus allowing effective interventions at an early course of the illness are, therefore, desirable. Neuroanatomical pattern classification is a powerful technique for image processing and analysis which allows both high-dimensional voxelwise group comparisons and classification of images at an individual basis. OBJECTIVES: To evaluate the diagnostic performance of a support vector machine (SVM)-based complex morphological pattern classifier was used to discriminate different non-affective and affective psychotic disorders at the first episode using a population-based approach to recruit both cases and healthy controls, and also to predict 1-year prognosis (i.e., remitting versus non-remitting course) in a group of patients with first-episode schizophrenia. METHODS: A sample of 62 patients with first-episode schizophrenia/ schizophreniform disorder, 23 cases presenting with their first-episode of psychotic mania (bipolar I disorder, BD-I) and 19 individuals with psychotic major depressive disorder (MDD) was studied with 1.5T structural magnetic resonance imaging (MRI), as well as a pool of 89 epidemiologically recruited controls. T1-weighted images were first registered to a common template through a robust mass-preserving routine allowing regional volumetric analysis. A high-dimensional multivariate classification method based on dimensionality reduction and SVM was employed to identify the best and most parsimonious set of morphological features that discriminate each psychotic group (schizophrenia/ schizophreniform disorder, BD-I & psychotic MDD) from subgroups of age, gender and educationally-matched healthy controls. The abnormalities scores generated by the classifier were analyzed with a ROC curve analysis and a high-dimensional spatial map of the brain regions that constitute a pattern of brain tissue distribution characteristic of each of the non-affective and affective groups relative to controls was created. RESULTS: The SVM-classifier afforded modest discrimination between subjects with first-episode schizophrenia/ schizophreniform disorder and controls, with an area under the curve (AUC) value of 0.75 and overall accuracy of 73.4%. The resulting discriminative spatial map revealed a complex pattern of regional volumetric abnormalities affecting both gray and white matter fronto-limbic regions bilaterally, long associative fasciculi, besides the third and lateral ventricles. A poor diagnostic performance was observed in the pairwise comparisons between BD-I and psychotic MDD versus controls. Also, the SVM-classifier failed to predict 1-year prognosis (remitting versus non-remitting course) in the first-episode schizophrenia group. CONCLUSION: The present results suggest that at the population level and using a real world sample of affective and non-affective psychotic patients with comorbid substance use disorders and variable disease course, we failed to achieve good discrimination between schizophreniform and affective forms of first-episode psychosis, and also in predicting 1-year prognosis of first-episode schizophrenia patients, using structural images

Psychotic disorders including bipolar disorder and schizophrenia are a leading cause of disability across the world but the underlying pathophysiological mechanisms remain poorly understood. Available treatments are inadequate for some sets of symptoms as is the case for negative symptoms in schizophrenia. Alterations in brain connectivity, synaptic plasticity, N-methyl D aspartate receptor (NMDAR) signalling and calcium homeostasis have been suggested to contribute to these disorders. However, the particular transcriptional programmes altered in these disorders are not fully characterised. Previous data suggested that the transcription factors specificity protein 4 (SP4) and SP1 may be involved in the pathophysiology of psychotic disorders. We hypothesized that the expression and/or function of SP4 and SP1 may be altered in psychotic disorders through the regulation of transcriptional programmes involved in neuronal patterning, synaptic plasticity and glutamate signalling. In this doctoral Thesis we aimed to characterise the contribution of SP4 and SP1 transcription factors to the pathophysiology of psychotic disorders. By using real time quantitative RT-PCR and/or immunoblot techniques, we analysed the expression of SP factors, of SP4 S770 phosphorylation and/or of selected SP-regulated gene targets in at least one of the following substrates: (i) rat cerebellar granule neurons (CGNs), (ii) the postmortem brains of bipolar disorder, schizophrenia and control subjects, (iii) peripheral mononuclear blood cells (PMBC) of first-episode psychosis, and (iv) the rodent hippocampus after NMDAR blockade and antipsychotic treatment. We found that membrane depolarisation regulates SP4 protein levels in CGNs by preventing SP4 degradation via the ubiquitin-proteasoma pathway and that lithium prevents SP4 degradation and increases SP1 gene expression in non-depolarising conditions. In postmortem human tissue, we found a reduction in protein but not mRNA expression of SP4 and SP1 in the cerebellum in subjects with bipolar disorder and in subjects with more severe negative symptoms in schizophrenia. We have also found reduced expression of protein and mRNA levels of SP4 in the prefrontal cortex in bipolar disorder and of SP1 in the same region in schizophrenia, suggesting a disorder-specific regulation in this area. In contrast, both SP4 and SP1 protein and mRNA levels were increased in the hippocampus in schizophrenia. Consistent with this, we also observed an increase of SP1 and SP4 protein levels in the hippocampus of a mouse model of psychosis, but not in the hippocampus of a rat model of chronic antipsychotic treatment, suggesting that this upregulation may be present from the early stages of psychosis. We further characterised the phosphorylation of SP4 at serine 770 (S770), which is regulated by membrane depolarisation and NMDAR activity. We found an increase of SP4 S770 phosphorylation in conditions where SP4 protein levels are reduced, namely in the cerebellum of bipolar disorder and of schizophrenia patients with more severe negative symptoms, as well as in PMBC in first-episode psychotic patients. These results suggest that an imbalance in SP4 abundance may be regulated by NMDAR-dependent SP4 phosphorylation in the brain. Moreover, we found that reduced expression of NR2A and DRD2 in the cerebellum of schizophrenia patients correlated with more severe negative symptoms and SP protein levels. Additionally, we show here evidence for an imbalance in the SP4-NWK2-NR1 pathway in the cerebellum of patients with bipolar disorder. This pathway is involved in NR1 subunit availability on the cell surface, suggesting that SP4 could contribute to altered NR1 receptor trafficking in psychotic disorders. Together, the results presented in this Thesis suggest an imbalance in SP4 and SP1 transcription factors in the brains of patients with bipolar disorder and schizophrenia that may contribute to alterations in NMDAR receptor signalling and thereby to the impaired synaptic plasticity and altered brain connectivity observed in psychotic disorders.

Introduction: Young people recovering from first episode psychosis experience a high degree of emotional distress and co-morbidity. Depression and social anxiety are highly prevalent following first episode psychosis and have been associated with poorer outcome, increased risk of suicide and lower quality of life. However, there is little research examining how these emotional difficulties relate to the course of psychotic symptoms and subsequent adaptation and recovery. The primary aim of this research was to establish a grounded theory of the experience of mood and anxiety related difficulties in young people who experience a first episode psychosis. Secondly, the research aimed to establish the underlying psychological factors contributing to the relationship between psychosis and affective dysfunction. Method: The study used a mixed-methods design with primacy given to the qualitative component (QUAL+quan). Young people (n=10) who had experienced a first-episode of psychosis were interviewed and completed measures of depression, social anxiety and recovery. Interviews were transcribed and analysed using a social constructivist version of grounded theory. Quantitative measures were integrated with the qualitative data, providing a framework for re-examining inferences made in the qualitative analysis. Results: The overarching theme to emerge was the experience of a developmental trajectory of psychosis. Seven key categories were identified: The build up; coping; breaking point; facing diagnosis; impact of illness; getting stuck and; moving on. Isolation, low mood and anxiety were universal outcomes and appeared to be mediated by maladaptive forms of coping and mood regulation in addition to psychological appraisals and negative illnessrelated experiences. Conclusions: The findings suggest that depression and social anxiety are not co-morbid features of psychosis but are intrinsically linked to the underlying processes involved in coping with and adapting to psychosis. Strengths and limitations of the research are discussed and implications for clinical practice and further research are reviewed.

Background: Physiological changes during pregnancy are often accompanied by reduced sleep quality, sleep disruptions, and insomnia. Studies conducted among men and non-pregnant women have documented psychiatric disorders as common comorbidities of insomnia and other sleep disorders. However, no previous study has examined the association between stress-related sleep disturbances and psychiatric disorders among pregnant women. Methods: This cross-sectional study included a total of 2051 pregnant women in Peru. The Spanish-language version of the Ford Insomnia Response to Stress Test (FIRST-S) was used to assess sleep disruptions due to stressful situations. Symptoms of antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) were examined using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7 and PTSD Checklist – Civilian Version, respectively. High risk for psychosis was assessed using the Prodromal Questionnaire. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). Results: Stress-related sleep disturbance was reported by 33.2% of women. Of all women, 24.9% had antepartum depression, 32.2% had generalized anxiety disorder, 30.9% had PTSD, and 27.6% were assessed as having a high risk of psychosis. After adjusting for confounders, women with stress-related sleep disturbances were more likely to experience antepartum depression (OR = 2.74; 95%CI: 2.22–3.38), generalized anxiety disorder (OR = 2.48; 95%CI: 2.04–3.02), PTSD (OR = 2.36; 95%CI: 1.93–2.88), and high risk for psychosis (OR = 2.07; 95%CI: 1.69–2.54) as compared to women without stress-related sleep disturbances. Conclusions: Stress-related sleep disturbances during pregnancy are associated with increased odds of psychiatric disorders. Inquiring about stress related sleep disturbances during antenatal care may be beneficial for identifying and caring for women at high risk of psychiatric disorders.
Revisión por pares

Background and objectives: Whilst Active and Receptive Music Therapy techniques have been widely researched and are employed within a range of contexts and with diverse client populations, this study reports on their specific qualitative musical and verbal affordances in major depressive disorder and schizophrenia-spectrum psychotic disorders. The study also describes and compares the respective and joint contributions of the music therapy techniques in giving rise to the affordances as well as reporting on the similarities and differences within and between diagnostic groups. This is the first study of its kind within the South African context. Methods: A qualitative research approach using a case study design, sampled purposefully twenty patients of the above mentioned diagnostic groups for participation in this study comprising a course of eight twice weekly music therapy sessions. The primary data sources were transcribed video recordings of therapy sessions and an individual in-depth semi-structured interview after the course of therapy. Clinical session notes served as a corroborative data source. In-depth content and thematic analysis explored and compared qualitative affordances during music therapy comprising active and Receptive Music Therapy techniques. The qualitative affordances under investigation were i) musical qualities, and ii) verbal expressions. Emerging from these affordances were the respective and combined affordances of the music therapy techniques as well as the similarities and differences between the diagnostic groups. Findings: Thirteen themes emerged from the analysis of clients' verbatim verbal responses to both active music making and Receptive Music Therapy techniques. These themes are: i) not to feel; ii) to do or not to do; iii) grappling with the desired future; iv) hurt and fear of undesirable outcomes; v) sadness, brokenness and futility; vi) anger, trust and vulnerability; vii) desire for connection with and affection of others; viii) barricaded from being present, now; ix) tensing and un-tensing; x) personal relating to one’s musical expression; xi) reflections on the music and music making in therapy; xii) resilience and courage and xiii) invigoration and liberation. The Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and x) resolution and arrival. The emerging themes express the extent of musical and verbal expression of all clients representing both diagnostic groups. Most saliently among clients with depression the affordances were the themes on accessing creativity, accessing and articulating internal feelings, experiencing resilient parts of self, reflecting on and integrating symbolic material, motivation to act and extending musical and verbal expression during social interaction. Among clients suffering from schizophrenia spectrum disorder, the most striking affordances were experiences of regularity and flow within disorganization, orientation to ‘here and now’ experiences through active music making and working with symbolic material expressed on a continuum of concrete to abstract. Clients from both diagnostic groups experienced a reduction in unwanted symptoms as expressed through increased energy levels, experiences of pleasure in music making and spontaneous musical and verbal self-expression. Conclusion: This study revealed qualitative affordances of specific music therapy techniques expressed through verbal content and musical qualities. These showed responses within a therapeutic relationship that express inter- and intra-personal connection, give voice to what is not always verbally accessible and facilitate multi-sensory, creative experiences, increased motivation, emotional expression, and the reclamation of energy, spontaneity and resilience.
Thesis (PhD)--University of Pretoria, 2017.
Psychiatry
PhD
Unrestricted

Postpartum depression affects some 10% to 20% of mothers. Its impact on the health and well-being of mothers and their infants is well documented. If not identified and addressed early, it can result in emotional burden, costly hospitalization and treatment, and, at worst, suicide and or infanticide. Empowerment theory was the conceptual framework for this hermeneutic phenomenological study. The purpose was to understand the lived experiences of the screening and treatment processes of 10 women from New York City experiencing postpartum depression and their perceived adequacy of the treatment received. In-depth interviews were used to investigate participants' lived experiences of the screening and treatment processes for their postpartum depression and to explore the extent to which they percieved that their emotional needs were met. From the responses to the interview questions, 6 themes emerged: crying and stress during and after pregnancy, inadequate assessment, feeling bad or unlike oneself, lack of understanding, needing to cope, and prayer was essential for recovery. Participants had tearfulness that began during pregnancy and intensified during the postpartum period, were ineffectively assessed, exhibited bizarre behaviors that could not be explained, had little understanding of what they were experiencing, and were sometimes misunderstood by others. Further, participants at times sought treatment on their own in order to cope. Some reported that prayer was central to the restoration of their mental health. Insights gained through this study can be utilized to foster positive social change by heightening awareness and assisting health care providers in planning appropriate screening and treatment to meet the individual needs of women with postpartum depression.

Paper one is a metasynthesis of studies exploring mothers' experiences of recovery from postnatal mental illness. Four databases were systematically searched using key words and index terms to identify the qualitative literature exploring mothers' experiences of recovery from postnatal mental illness. Fourteen studies met the inclusion criteria and were critically appraised and synthesised. These papers reported the views of 395 women's experiences of recovery from postnatal mental illness. Five core themes emerged from the synthesis to describe four key processes that facilitate recovery. This experience begins with recognising the problem through crisis and relational distress. Women then go through the process of seeking help which consists of subthemes of accepting help and help to access help. The next process in the in the journey is achieving recovery which includes subthemes of sharing with others like me, coping strategies and noticing recovery. The final process of maintaining recovery consists of incorporating coping strategies into daily life; acquiring a different model of motherhood and processing the experience. The role of the family was interwoven through each stage of recovery. Recommendations were made for professionals who come into contact with this group of women and their families. The review highlighted gaps in the existing evidence and made recommendations for future research. The findings and limitations were discussed with reference to the existing literature. Paper two explored the role of the baby in 12 mothers' experiences of recovery from psychosis after childbirth. A thematic analysis of the data identified three core themes that described the role of the baby in the mothers' recovery. Findings revealed that the baby was central to women's recovery and could be experienced as both helpful and unhelpful. The baby interacted with the mother; increasing self efficacy and reducing emotional distress. The baby could act as a barrier to recovery by increasing the women's emotional distress and hindering access to help and self care. The findings recommended that women receive specialist treatment in mother and baby units where they can access interventions that support parent-infant interactions. The findings of the study add to the existing evidence base on recovery from psychosis after childbirth and highlighted areas for future research. Paper three is a critique of the research carried out in Papers one and two. This paper discussed the rationale for the research design in both papers. Approaches to data sampling and data analysis are reviewed with reference to researcher reflexivity. The search strategy and critical appraisal of techniques of the metasynthesis are also critiqued. Paper three closes with personal reflections and conclusions drawn from both papers.

Women's accounts of 'puerperal psychosis' (PP) and 'postnatal depression' (PND) were analysed using a qualitative approach (Interpretive Phenomenological Analysis). The study aimed to explore experiences of PP and PND from women's own perspectives; to see whether accounts of PP and PND can be differentiated from each other; and to see whether taking a gendered perspective and drawing on psychological theories of psychosis can offer ways of understanding the experience of PP. Although only women with a diagnosis of PP reported unusual beliefs or hearing voices (as would be expected since it was these reports that resulted in the diagnosis), there were no differences between groups on other forms of distress such as low mood, anxiety and fear of harm to the baby. There were also no differences in the social and material contexts of women's lives (e. g. financial difficulties, lack of support). The importance of exploring the social and relational context of unusual experiences is emphasised and the content of 'delusions' 'hallucinations' 'paranoia' and 'rumination' (traditionally viewed as incomprehensible), as well as feelings of depression, were found to be related to the difficult transition to motherhood and ambivalence about pregnancy, childbirth and the baby within the context of overwhelmingly positive sociocultural discourses of motherhood. The impact of this context on self-identity (as a woman and a mother) and on having to take control and responsibility whilst remaining powerless in their wider context, were themes common to all six women. The clinical and theoretical implications are discussed, and areas identified for further research.

Las personas que experimentan síntomas seudopsicóticos (SSP) presentan un riesgo elevado de sufrir trastornos psicóticos. Sin embargo, asociaciones encontradas entre SSP y trastornos no psicóticos sugieren que la relevancia clínica de los SSP no se limita a la psicosis y por lo tanto, investigar el rol de síntomas adicionales tales como la depresión, puede mejorar la capacidad de predecir el riesgo de desarrollar trastornos psicóticos. Asimismo, estudiar las habilidades en teoría de la mente (ToM), área cognitiva que sufre alteraciones en pacientes con esquizofrenia, en adolescentes de la población general, puede contribuir a clarificar si las personas consideradas en riesgo presentan déficits en ToM. La evidencia sugiere que los déficits en ToM no son exclusivos de los pacientes sintomáticos y que una mayor comprensión de la naturaleza de estas alteraciones se puede lograr a través su estudio antes del inicio del trastorno. Objetivos: (1) examinar la presencia de SSP positivos y negativos y su asociación con síntomas depresivos en una muestra de adolescentes de la población general; (2) analizar la presencia de subtipos de SSP positivos y negativos, y (3) examinar el funcionamiento de ToM, su asociación con esquizotipia psicométrica, SSP y síntomas depresivos. Método: los participantes en este estudio transversal fueron adolescentes con edades entre los 13 y 17 años, estudiantes de secundaria en escuelas de Barcelona, España. Para establecer la presencia de subtipos de SSP positivos y negativos se llevaron a cabo análisis factoriales de las subescalas que evaluaban estos síntomas. La asociación entre los subtipos de síntomas positivos y negativos y los síntomas depresivos se examinó mediante el análisis de regresión múltiple. Resultados: Se identificaron dimensiones de SSP y esquizotipia en esta muestra de adolescentes de la población general. Cuatro factores de síntomas positivos (ideación persecutoria, ideación de grandiosidad, experiencias alucinatorias/de primer rango y pensamiento auto-referencial) y tres factores de síntomas negativos (retraimiento social, aplanamiento afectivo y abulia) fueron identificados. Se encontraron relaciones entre los subtipos de síntomas positivos y negativos y síntomas depresivos, así: la ideación persecutoria y las experiencias alucinatorias y de primer rango se asociaron a puntuaciones más altas en síntomas depresivos, mientras que la ideación de grandiosidad se asoció a puntuaciones más bajas en depresión. No se encontró asociación entre depresión y pensamiento autorreferencial. Se encontraron también asociaciones entre subtipos de síntomas negativos y depresión: retraimiento social y abulia se asociaron positivamente al auto-informe de síntomas depresivos, mientras que el aplanamiento afectivo no se asoció a depresión. No se observaron diferencias en las habilidades de ToM entre los adolescentes con puntuaciones totales más altas en SSP o esquizotipia comparados con los adolescentes con puntuaciones totales más bajas. Las puntuaciones altas en la escala de experiencias inusuales que evalúa esquizotipia positiva, al igual que la subescala de experiencias de primer rango, se asociaron con déficits en ToM, mientras que la ideación persecutoria se asoció a un mejor desempeño en ToM. El desempeño en ToM no se asoció a pensamiento mágico ni a experiencias alucinatorias. Los síntomas negativos y la esquizotipia negativa no se relacionaron con el desempeño en ToM. Un mejor desempeño en ToM se asoció a mayor no-conformidad impulsiva. Conclusiones: los hallazgos presentados en esta tesis confirman que no todos los tipos de SSP positivos y negativos se asocian con depresión y por lo tanto, podrían conferir diferente vulnerabilidad a sufrir trastornos psicóticos. Las alteraciones en ToM no se limitan a la fase aguda de un trastorno psicótico, y podrían asociarse a la esquizotipia positiva y a experiencias de primer rango. Estos hallazgos sugieren que es posible identificar alteraciones en ToM durante la adolescencia antes del inicio de cualquier trastorno.
Individuals who report psychotic-like experiences (PLEs) are at significantly increased risk for clinical psychotic disorders. However, associations between PLEs and non-psychotic disorders indicate that the clinical relevance of PLEs is not limited to psychosis and thus, investigating the role of additional symptoms, such as depression, may improve the capacity to predict risk of developing psychotic disorders. Additionally, studying theory of mind (ToM) abilities, one of the cognitive areas impaired in schizophrenic patients, in adolescents from the general population may contribute to clarify whether ToM deficits are present in at-risk individuals before the onset of the illness and derived impairments. Evidence suggests that ToM impairments are not exclusive of symptomatic patients, and that further understanding of the nature of ToM dysfunction in schizophrenia might be achieved through examination of ToM impairments from the early phases and even before the onset of the illness. Objectives: this thesis was aimed at (1) examining the presence of both positive and negative PLEs and their association with depressive symptoms in a community sample of adolescents; (2) analysing the presence of subtypes of positive and negative PLEs dimensions in adolescents of the community, and (3) exploring ToM functioning, its association with psychometric schizotypy, PLEs, and depressive symptoms, in a sample of adolescents from the general population. Method: participants in this cross-sectional study were adolescents aged between 13 and 17 years, attending compulsory secondary education in schools from Barcelona, Spain. To establish the presence of subtypes of positive and negative PLEs, separate principal component factor analyses of the CAPE positive and negative subscales were performed. Multiple linear regression analysis was conducted to examine the association between specific CAPE positive and negative PLE subtypes and depressive symptoms. Results: PLEs and psychometric schizotypy dimensions were present in this community sample of adolescents. Four factors of positive symptoms (persecutory ideation, grandiose thinking, first-rank-hallucinatory, and self-referential thinking) and three factors of negative symptoms (social withdrawal, affective flattening, and avolition) emerged from the analysis. Different relationships between subtypes of positive PLEs and depressive symptoms were found: persecutory ideation and first-rank/hallucinatory experiences related to higher scores on the depressive symptoms scale whilst grandiose thinking related to lower scores on depression. No association with self-referential thinking was found. Associations between subtypes of the negative dimension and depression were also found: social withdrawal and avolition were positively associated with the self-report of depressive symptoms, while affective flattening did not relate to depression. No differences were found in ToM abilities in adolescents with higher global scores on schizotypy or PLEs relative to those with lower global scores. Higher scores on the unusual experiences subscale assessing positive schizotypy and on first-rank experiences were associated with poorer ToM ability, whereas persecutory beliefs were related to better ToM performance. No association was found between ToM and magical thinking or hallucinatory experiences. Negative PLEs or negative schizotypy were not related to ToM abilities. In addition, an association between better mentalising abilities and higher impulsive nonconformity was found. Conclusions: these findings support the view that not all types of positive and negative PLEs in adolescence are associated with depression and, therefore, may not confer the same vulnerability for psychotic disorders. ToM impairments are not restricted to the acute phase of a psychotic disorder, and may be associated to positive schizotypy and first-rank experiences. These findings constitute evidence indicating that ToM impairments can be identified during adolescence before the onset of any psychotic disease.

This study examined the effect of three different nursing interventions in the management of women diagnosed as suffering from manic depressive psychosis. The thesis was presented in three parts. In Part One, an examination was made of the role of the nurse in caring for patients suffering from affective disorder in general. Four sub-studies were used to define the construct `routine nursing care'. These comprised: a critical appraisal of (1) the training and (2) the examination of Scottish nursing students; Scottish nurses' perceptions of their role in caring for, (3) patients with manic depresssive psychosis and (4) patients with affective disorder in general. These sub-studies suggested that psychiatric nurses were trained to offer a general, supportive, pattern of care to all patients suffering from affective disorder. No clear difference was found between the role perceptions of nurses caring for `depressed' patients in general, and those caring for manic depressive patients in particular. In Part Two, a further sub-study (5) examined a specific psychological construct, locus of control, within the context of women diagnosed as manic depressive psychosis, in remission. This study suggested that women with a history of depression-only, differed from a normative sample on one scale, with both depression-only and mania and depression subjects differing from each other, and from the normative sample on a second locus of control scale. In a final sub-study (6) a new locus of control scale was developed to measure the patient's expectations of her capacity to influence her status as a sufferer from affective disorder. Sub-studies 5 and 6 suggested the possible role played by the locus of control construct, as a mediating factor in the precipitation and maintenance of major affective disorder. In Part Three, the main (experimental) study compared the effect of three discrete nursing interventions, Routine Nursing Care, Self Evaluation and Modified Cognitive Therapy, on measures of four dependent variables characteristic of depression, and satisfaction with care and treatment. The results suggested that, despite the absence of significant between-group differences on all measures of the dependent variables, the Modified Cognitive Therapy intervention showed more clinically significant changes on three of the clinical variables, and that subjects in the MCT group become more internalised on the locus of control measure. This, suggests that the MCT group subjects' view of their capacity to control external sources of reinforcement, might have increased as a function of exposure to the training in self-management inherent in the MCT intervention. The implications of these findings for psychiatric nursing education and practice are discussed.

Schizophrenia is a debilitating mental disorder that causes a large economic burden and is prevalent across all cultures and countries around the world. Although both environmental factors and genetics are known to play an important role in the etiology of schizophrenia, the exact role of genetics and its interaction with environmental factors in an individual’s predisposition to develop schizophrenia is poorly understood. Schizophrenia is characterized by symptoms that include positive symptoms (e.g. delusions, hallucinations, disorganized thinking and speech), negative symptoms (e.g. avolition, anhedonia, depressive-like behavior), and cognitive dysfunctions (e.g. executive functioning deficits in learning and memory, attention, and vigilance). Genomic screening has identified polymorphisms of the vesicular monoamine transporter 1 (VMAT1) gene (SLC18A1) that are associated with schizophrenia and bipolar disorder. The current study represents the first extensive phenotyping of both young and aged mice in which the VMAT1 gene (SLC18A1) has been deleted. The results demonstrated behavioral effects of deleting the VMAT1 gene that may relate to aspects of schizophrenic-like behavioral changes in this model. Specifically, young VMAT1 knockout mice displayed significant deficits in sensorimotor gating in the prepulse inhibition (PPI) task and in the acquisition of operant learning in the autoshaping task. When exposed to a mild stressor (24 hours of food deprivation), young VMAT1 knockout mice displayed a significant reduction in locomotor activity that was not evident under free-feeding conditions. Thus, young VMAT1 knockout mice showed deficits in tasks that model positive symptoms and cognitive deficits seen in schizophrenia; however, they did not display differences in behaviors related to models of the negative symptoms of schizophrenia or deficits in tasks designed to measure motor skills. While less extensive phenotyping was conducted in aged VMAT1 knockout mice, there were no significant deficits evident in any of the assays conducted in older animals. These findings demonstrated that deletion of the VMAT1 gene has behavioral effects that appear to be mediated by changes in brain monoamine function and changes in response to stressors (i.e. food deprivation) that may reflect changes in adrenal gland monoamine function.

Os transtornos afetivos são altamente prevalentes dentre os transtornos mentais, principalmente Transtorno Afetivo Bipolar (TAB) e Depressão Maior Unipolar (DMU), apresentando altas taxas de morbi-mortalidade. Estudos prévios de Ressonância Magnética (RM) têm identificado anormalidades estruturais cerebrais em indivíduos com TAB e DMU quando comparados a controles normais. Entretanto, nenhum destes estudos foi realizado a partir da comparação direta entre pacientes com DMU e TAB de início recente, nem comparou separadamente tais grupos com amostras representativas de controles assintomáticos provenientes de mesma região geográfica. No presente estudo, definimos a priori que regiões do circuito córtico-límbico-talâmico-estriatal estariam alteradas quando comparados indivíduos com TAB, DMU e controles normais diretamente entre si, em amostra de pacientes com quadros graves de sintomatologia psicótica e pareada com controles normais selecionados na mesma área geográfica dos pacientes. Foram selecionados 46 pacientes (20 com DMU e 26 com TAB) que tiveram contato pela primeira vez com serviço de saúde mental após início de sintomas psicóticos e 62 controles normais. Tanto pacientes quanto controles foram submetidos à RM em aparelho de 1,5 Tesla. Os diagnósticos foram baseados no DSM-IV e confirmados após 1 ano da realização da RM. As imagens foram analisadas pelo método automatizado de processamento denominado morfometria baseada no voxel (voxel-based morphometry). A comparação entre os grupos mostrou redução significativa de substância cinzenta regional em pacientes com DMU comparados aos controles (p<0,05, corrigido para comparações múltiplas) em duas regiões cerebrais selecionadas a priori: córtex pré-frontal dorsolateral (CPFDL) bilateralmente e giro parahipocampal posterior esquerdo. Na comparação direta entre pacientes com DMU e TAB encontramos uma redução de substância cinzenta de CPFDL direito em pacientes com DMU, como tendência a significância estatística (p<0,10, corrigido para comparações múltiplas). Nossos achados mostram que anormalidades volumétricas de CPFDL e região temporal medial estão presentes em pacientes com DMU em primeiro episódio psicótico, mas não em pacientes com TAB com gravidade de sintomas semelhante.
Affective disorders are highly prevalent mental disorders, mainly Major Depressive Disorder (MDD) and Bipolar Disorder (BD), with high morbidity and mortality rates. Previous morphometric magnetic resonance imaging (MRI) studies have identified brain volumetric abnormalities in samples of subjects suffering from MDD or BD. However, none of these have conducted direct brain volume comparisons between patients with recent-onset MDD and BD, nor contrasted them separately against representative groups of asymptomatic controls recruited from exactly the same environment. In the present study, we defined a priori that brain regions involved in cortico-limbic-thalamic-striatal circuits would present volume abnormalities when comparing subjects with MDD and BD with psychotic features, in their first contact with the health care system in Brazil, and a control sample of next-door asymptomatic neighbors. Forty-six patients (20 MDD and 26 BD) and 62 controls were examined with MRI, using an equipment of 1.5 Tesla. Diagnoses were based on DSM-IV, and confirmed one year after scanning. Image processing was conducted using voxel-based morphometry methods. Between-group comparisons showed significant regional gray matter deficits in MDD subjects relative to controls (p<0.05, corrected for multiple comparisons), involving two brain regions where abnormalities in mood disorder patients had been predicted a priori: the dorsolateral prefrontal cortex (DLPFC) bilaterally and the left posterior parahippocampal gyrus. In the direct comparison between MDD and BD patients, the right-sided finding of decreased DLPFC gray matter in the former group retained trend levels of significance (p<0.10 corrected). Our findings indicate that significant structural abnormalities of the DLPFC and medial temporal region are present in patients with MDD in their first episode with psychotic features, but not in BD subjects with symptoms of similar severity.

Objective: The aim of the current study was to investigate the differences in baseline characteristics and three-year outcomes between two diagnostic categories with presentation of first-episode psychosis: bipolar affective disorder (mania with psychotic features) and schizophrenia. The comparison was based on pre-treatment characteristics, clinical presentation, symptomatic and functional outcomes, and engagement in risk behaviours. Methods:461 schizophrenic patients and 54 bipolar affective disorder (BAD) patients between the ages of 15 to 25 years from a local first-episode psychosis treatment program within the years2001 to 2003 were studied. Researchers collected detailed data on baseline and three-year follow up variables from systematic medical file review for statistical analyses. Results: At service entry, compared to schizophrenic patients, bipolar affective disorder(BAD)patients exhibited more prominent positive symptoms (p = 0.01), were younger at first presentation and had a higher unemployment rate (p < 0.01), were more likely to have acute onset of psychosis, shorter duration of untreated psychosis (DUP), a higher rate of hospital admission within first month after initial contact, and lower pre-treatment functioning (Social and Occupational Functioning Assessment Scale (SOFAS), p < 0.001). There was no significant difference in gender, education level, age of onset and pre-treatment risk taking behaviours. After applying univariate analysis of variance (ANCOVA)by controlling baseline variables that showed significant differences, the three year follow up reveals that schizophrenic patients displayed fewer numbers of hospitalization (p <0.01)with no difference in the total length (days) of hospitalization, more prominent positive symptoms(p < 0.01), poorer functioning at year 3 (p <0.05), and consistently significant lower employment rate at 12 month (p < 0.001), 24 month (p < 0.001) and 36 month (p < 0.01). Finally, more schizophrenic patients received social benefits (p < 0.05). Conclusion: The outstanding baseline poorer functioning level of bipolar affective disorder patients have progressively made a modest improvement in functional outcomes at the end of three-year follow up. BAD patients also displayed a marked improvement with fewer positive symptoms in the follow up. The results suggest a differentiation in symptomatology and the course of illness between bipolar affective disorder and schizophrenia with first-episode psychosis. In coherence with other scholastic literature, duration of untreated psychosis (DUP) associates with remission(Crumlish et al., 2009;Chang et al., 2012a), positive symptoms(Barnes et.al., 2008; Chang et.al., 2012b; Clarke et al., 2006; Crumlish et.al., 2009;), and functional outcomes(Barnes et al., 2008; Chang et al., 2012b; Clarke et.al., 2006; Crumlish et.al, 2009; Fusar-Poli et al., 2009). Moreover, further exploration about the diagnostic-specific therapeutic window for early intervention, symptoms management, and rehabilitation strategies in occupational training are in demand.
published_or_final_version
Psychological Medicine
Master
Master of Psychological Medicine

RESUMO: De acordo com o estado da arte, existem intervenções psicofarmacológicas, psicológicas e psicossocias, com evidência científica dos seus resultados, no tratamento de pessoas com esquizofrenia e perturbação esquizoafectiva. No entanto, muitos destes doentes, não procuram ajuda dos serviços de saúde mental, não recebem os referidos cuidados ou não são detectados nem seguidos por estes. Esta realidade levou ao desenvolvimento de programas integrados, intervenções e estudos mais específicos, nomeadamente para tentar ultrapassar os obstáculos na acessibilidade aos cuidados de saúde e na continuidade de seguimento destes doentes. No conjunto das dificuldades apuradas, as questões da exequibilidade (feasibility) e da implementação, têm tido particular relevo na literatura científica recente, bem como a melhor forma de vencer as respectivas barreiras e adaptar essas intervenções às varias realidades, culturas e recursos. Objectivos: Objectivos gerais:1) Avaliar a exequibilidade e a implementação inicial de um programa de cuidados integrados, para pessoas com esquizofrenia ou perturbação esquizoafectiva, no contexto clínico das equipas de saúde mental comunitárias de um departamento de psiquiatria do Serviço Nacional de Saúde, em Portugal, com os recursos materiais e humanos existentes; 2) Avaliar o impacto deste programa, nestes doentes e na respectiva prestação de cuidados de saúde mental. Metodologia. Elaborámos um programa de cuidados integrados (Programa Integrar) com base no modelo clínico de case management, com seguimento mantido e integrado. Cada doente passou a ter um terapeuta de referência, um plano individual de cuidados e manteve o seguimento com o seu psiquiatra assistente. Foram seleccionadas intervenções, nomeadamente, psicoeducativas, familiares, estratégias para lidar com os sintomas e a doença, prevenção de recaídas e intervenções para melhorar o funcionamento social e ocupacional. A estas intervenções foi sempre associado o tratamento psicofarmacológico. O estudo delineado incluiu dois componentes: avaliação da exequibilidade e implementação inicial do programa de cuidados integrados (componente A) e avaliação do impacto deste programa (componente B), através de um estudo de intervenção, prospectivo, naturalista, não aleatorizado e não ontrolado. A amostra do estudo resultou das sucessivas referenciações, para o Programa Integrar, de pessoas com os diagnósticos de esquizofrenia ou perturbação esquizoafectiva, seguidas nas cinco equipas de saúde mental comunitárias do Departamento de Psiquiatria do Centro Hospitalar de Lisboa Ocidental, com uma área assistencial correspondente a uma população de, aproximadamente, 400 000 pessoas. Definimos etapas, estratégias, parâmetros e indicadores para o estudo da exequibilidade do programa. Efectuámos a monitorização e a avaliação de tarefas, procedimentos e intervenções recomendadas aos terapeutas de referência. Realizámos duas avaliações, uma no início do programa e outra após um ano de intervenção. Foram avaliadas as seguintes dimensões (com indicação do acrónimo do instrumento de avaliação utilizado entre parêntesis): psicopatologia (BPRS), depressão (MADRS), necessidades (CAN), incapacidade (DAS), actividade social e ocupacional (SOFAS), atitude em relação à medicação (DAI), insight (SAI), qualidade de vida (WHOQOL-S) e satisfação (POCS). Resultados: Dos 146 doentes que foram incluídos no estudo, 97 (66%) eram do sexo masculino e 49 (34%) do sexo feminino, com uma idade média de 36 anos. Destes oentes,116 (79,4%)tinham o diagnóstico (ICD10) de esquizofrenia e 30 (20,6%) de perturbação esquizoafectiva. Os restantes dados sociodemográficos eram típicos de populações afins em serviços de saúde mental nacionais. Do total de doentes (146) que iniciaram o estudo, 26 (18%) abandonaram o seguimento neste programa. Para o componente A da investigação (estudo de exequibilidade) salientamos: exerceram funções a totalidade (15) dos terapeutas de referência que receberam formação, 76 % efectuaram o número mínimo recomendado de sessões / ano por doente (≥18), 44,9 fizeram o número mínimo de sessões familiares pretendido (≥ 3). Nas intervenções mais específicas foram atingidos os objectivos em mais de 75% dos doentes, à excepção das intervenções domiciliárias (19,4%), prevenção do abuso de substâncias (45,4%) e do risco de suicídio (34,3%). O plano individual de cuidados foi realizado em 98 % dos doentes e em 38,9 % dos casos ocorreu a participação da família. Neste plano, a média de objectivos definidos foi de 5 e a média de objectivos atingidos correspondeu a 3 (p= 0,001). Na primeira avaliação, estavam a frequentar estruturas de reabilitação psicossocial 42 doentes (28,8%) e,12 meses após, esse número passou para 80 (74,1%).Também aumentou o número de doentes com actividade profissional a tempo completo, de 8 (7,4%) para 18 (16,7%). No componente B do estudo (avaliação do impacto do programa), em termos de psicopatologia, e para as pontuações médias globais do BPRS, ocorreu uma diminuição entre a primeira e a segunda avaliação (p=0,001), tal como nas subescalas: sintomas positivos (p=0,003), sintomas negativos (p=0,002), sintomas de mania (p=0,002) e sintomas de depressão/ansiedade (p=0,001). Na avaliação da depressão (p= 0,001) e da incapacidade (p=0,003), as diferenças foram significativas e favoráveis. O mesmo não sucedeu na atitude em relação à medicação (p=0,690) nem na escala de avaliação do insight (p=0,079). Em relação ao funcionamento social e ocupacional, qualidade de vida e satisfação dos doentes, ocorreu uma melhoria significativa da primeira para a segunda avaliação As necessidades sem resposta mais frequentes, na primeira avaliação, corresponderam aos itens: actividades diárias, contactos sociais, relações íntimas, relacionamento sexual, benefícios sociais, sintomas psicóticos, sofrimento psicológico, informação sobre a doença / tratamento e gestão/problemas de dinheiro. Para todos estes últimos nove itens, verificou-se uma diferença estatisticamente significativa, entre a primeira e a segunda avaliação, com diminuição destas necessidades, excepto nas relações íntimas, relacionamento sexual e nos problemas de dinheiro. Na distribuição dos três estados de necessidades, para todos os itens, diminuíram as necessidades sem resposta e as necessidades com resposta parcial e aumentaram as situações em que deixaram de se verificar necessidades relevantes. Dos resultados obtidos para outros indicadores clínicos e de utilização dos cuidados, será importante referir que na comparação do ano anterior com o ano em que decorreu o programa, o número de doentes da amostra internados diminuiu 64,1%, bem como a média do número de internamentos (p=0,001). Em relação à duração dos internamentos, no ano anterior ao programa, os 39 doentes internados, tiveram um total de dias de internamento de 1522, sendo que, no ano do programa, para os 14 doentes internados, o total foi de 523 dias. Em termos absolutos, ocorreu uma redução de 999 dias (menos 65,6% dias). Também se verificou uma diminuição de 45,6 % de recaídas (p=0,001).Discussão e conclusões A exequibilidade do programa de cuidados integrados permitiu a aplicação do modelo clínico de case management, com seguimento mantido e integrado, através do qual cada doente passou a ter um terapeuta de referência assim como, em 98% casos, um plano individual de cuidados. As famílias continuaram a ser o principal suporte para os doentes, mas surgiram dificuldades quando se pretendeu uma participação mais activa destas no tratamento.A diminuição do número e da duração dos internamentos constituíram importantes resultados com implicações não só em termos clínicos mas também económicos. Os valores obtidos, para as diferentes variáveis, também sugerem o impacto favorável do Programa Integrar a nível da psicopatologia, das necessidades, da incapacidade, do funcionamento social e ocupacional, da qualidade de vida e da satisfação dos doentes. O mesmo não sucedeu para o insight e para a mudança de atitudes dos doentes em relação à medicação, resultados que devem ser igualmente considerados em futuros reajustamentos deste programa ou no desenvolvimento de novos programas. Como principais conclusões podemos referir que: 1) Foi possível a exequibilidade de um programa de cuidados integrados inovador e a implementação inicial desse programa, para doentes com esquizofrenia ou perturbação esquizoafectiva, com os recursos humanos e materiais existentes, no contexto clínico das equipas de saúde mental comunitárias, de um departamento de psiquiatria e saúde mental, em Portugal; 2) Na avaliação do impacto do programa, os resultados obtidos indiciam potencialidades de aplicação, deste programa de cuidados integrados, com vista à melhoria clínica e psicossocial destes doentes. Devem ser realizados estudos de replicação, ou complementares à presente investigação, no entanto, os dados obtidos são encorajadores para o desenvolvimento de programas similares, a nível nacional e internacional, que possam beneficiar um grupo mais alargado de doentes.------------ABSTRACT: Although there are psychological and psychosocial interventions well supported by scientific evidence, which show benefit when combined with psychopharmacological treatments, we know that a significant number of people with schizophrenia or schizoaffective disorders, do not seek help from mental health services, do not receive the care mentioned and are not detected or followed-up by them. This reality led to the development of integrated programs, interventions and more specific studies, to try to overcome the obstacles in the accessibility to the health services and on the follow-up of these patients. Amongst the barriers identified, feasibility and implementation of those programs have been of special relevance in recent scientific literature, as well as the best way to overcome such difficulties and adapt the interventions to the various realities, cultures and resources. Objectives: General objectives were defined: 1) Assessment of the feasibility and initial implementation of an integrated care program, for people with schizophrenia or schizoaffective disorder, in the clinical setting of community mental health teams, in a psychiatric department from the national health service in Portugal; 2) Impact evaluation of the integrated care program, for these patients and their mental health care delivery. Methods: We drew up an integrated care program (Program Integrar) based on the clinical case management model, with continuous and integrated follow-up. Each patient got one case manager, an individual care plan and kept the same psychiatrist. Were selected the appropriated interventions, namely: psycho-educative, family-based interventions, strategies for dealing with the symptoms and the disorder, relapse prevention and interventions to improve social and occupational functioning. These interventions were always associated with psychopharmacological treatment. The investigation was outline with two parts: assessment of the feasibility and initial implementation of the Program Integrar (part A of the study) and impact evaluation of the program (part B of the study). We designed a naturalistic, prospective, intervention study, non-randomized and without control group. Our chosen sample was made with successive referrals of patients with the diagnosis of schizophrenia or schizoaffective disorder, followedup in one of the five community mental health teams of the Psychiatric Department of Centro Hospitalar Lisboa Ocidental, with a catchment area for a population of about 400 000 people. Different stages, strategies, criteria and indicators for studying the feasibility of the program and its implementation were set and the tasks, procedures and recommended interventions of the case managers were monitored and evaluated. We did two assessments with an interval of one year and we evaluated the following dimensions (the acronym of the assessment instrument used in brackets): psychopathology (BPRS), depression (MADRS), needs (CAN), disability (DAS), social and occupational functioning (SOFAS), attitude toward medication (DAI), insight (SAI), quality of life (WHOQOL-S) and satisfaction (POCS). Results: Of the 146 patients who started the study, 97 (66%) were male and 49 (34%) females with a mean age of 36 years. Of these, 116 (79,4%) were diagnosed (ICD10) with schizophrenia and 30 (20,6%) with schizoaffective disorder. The other socio-demographic data were typical of populations within Portuguese mental health services. Of all patients (146), who started the program, 26 (18%) of patients left the program (program dropout rate). Of the regarding part A of the study, which focused on feasibility, the following is of note: all professionals who had been trained for this purpose (15) acted as case manager, 76% did the recommended minimum number of sessions / year per patient (≥18) and 44,9% did the minimum number of family sessions desired (≥ 3). For the more specific interventions the parameters set out were met for more than 75% of patients, with the exception of domiciliar interventions (19.4%), prevention of substance abuse (45.4%) and suicide risk prevention(34.3%). The individual care plan was done for 98% of patients and in 38,9% of cases this involved family participation. For this plan the mean objectives defined were 5 and in average was achieved 3 (p=0,001). On the first assessment, 42 patients (28.8%) were attending psychosocial rehabilitation structures and 12 months later that number rose up to 80 (74,1%). Regarding their employment status, in the first assessment 8 (7,4%) were in full time employment and in the second evaluation the number rise to 18 (16,7%). For part B of the study (impact program evaluation), in terms of psychopathology, global mean scores for the BPRS, decreased (p=0,001), as did the four sub scales: positive symptoms (p=0,003); negative symptoms (p=0,002); manic symptoms (p=0,002) and symptoms of depression/anxiety (p=0,001). Both in the evaluation of depression (p=0,001), as in the assessment of disability (p=0,003), the differences were significant. However, this was not the case with attitudes towards medication (p=0,690) and with insight evaluation (p=0,079). In relation to social and occupational functioning, quality of life and patient satisfaction there was a statistically significant improvement from the first to the second assessment. The most commonly unmet needs in the first assessment were daily activities, social contacts, intimate relationships, sexual relations, social benefits, psychotic symptoms,psychological distress, information about the disorder / treatment and money problems money management. Of these, in the second assessment, all of those nine unmet needs showed significant improvement, excepted intimate relationships, sexual relations and Money problems / money management. In the distribution of the three states of needs for all items, it happened a decreased in unmet needs and partially met needs and increased in the situations where relevant needs were no longer found. For other clinical indicators it is important to note, when we compared the year prior to this program and the year after, there were fewer hospitalizations (reduction of 64,1% of admissions) and in the mean number of admissions (p=0,001). Regarding the length of hospitalization in the year prior to the program, the 39 patients admitted had a total of 1522 hospital days, and in the year of the program for the 14 hospitalized patients, the total was 523 days. In absolute terms, there was a reduction of 999 days (65,6%). There was also a 45,6% reduction of relapses (p = 0,001). Discussion and Conclusions: The feasibility of the integrated care program allowed the application of the clinical case management model, with continuous follow-up. Each patient got a case manager and in 98% of the cases they also got an individual plan of care. Families continued to be the main support for patients but, difficulties occurred when it was claimed a more active participation. The decrease in the number and duration of admissions were important findings with implications not only in clinical terms but also in economic field. The achieved results for the different variables can also indicate the favorable impact of this program, at the level of psychopathology, needs, disability, social and occupationa functioning, quality of life and patient satisfaction. The same did not happen for the evaluation of insight and in the changes of attitudes towards medication. These data should also be considered for future readjustments of this program and for the developing of new programs.Finally, the two-overview conclusions are: 1) It was possible the feasibility of an integrated care program and initial implementation of this innovative program, for patients with schizophrenia or schizoaffective disorder, with the human and material resources available in the clinical context of the community mental health teams, in a psychiatry and mental health department of the national health service in Portugal; 2) In assessing the impact of the program, the results suggest potential application of this integrated care program, to improve clinical state and psychosocial variables for these patients. There should be done studies to replicate these results, however the results obtained are promising for the development of similar programs at nationally and internationally level, that could benefit a wider group of patients.

O estudo dos sintomas neuropsiquiátricos em Doença de Alzheimer (DA) através do agrupamento destes em síndromes tem sido cada vez mais utilizado, uma vez que permitiria detectar diferenças em sua prevalência, em sua evolução, em relação a determinantes psicossociais e a correlatos neurobiológicos. O objetivo deste estudo foi identificar regiões de redução de substância cinzenta em áreas corticais associadas com sintomas e síndromes neuropsiquiátricos específicos, provenientes da Escala Inventário Neuropsiquiátricos (NPI), em pacientes com DA e comprometimento cognitivo sem demência (CIND). O método de morfometria baseada no voxel (VBM) com DARTEL (Diffeomorphic Anatomical Registration Using Exponentiated Lie Algebra) foi utilizado para verificar a correlação entre presença de sintomas e síndromes neuropsiquiátricos específicos e redução regional de volume de substância cinzenta em análise em todo cérebro e em regiões previstas a priori. As síndromes utilizadas foram SN1/Agitação (agitação, alterações de sono e apetite), SN2/Hiperatividade (desinibição, comportamento motor aberrante e irritabilidade), SN3/Afetiva (depressão e apatia) e SN4/Psicose (delírios e alucinações). A presença de delírios foi associada a volume de substância cinzenta reduzido em giro frontal inferior direito (BA45); depressão com xvii redução de substância cinzenta em giro temporal médio e inferior direito (BA 37/22) e giro frontal inferior (BA09-DLPFC) e giro parahipocampal esquerdos; ansiedade com redução em giro frontal médio esquerdo (BA10); e alterações de apetite com redução em córtex anterior cingulado esquerdo (BA32) em pacientes com DA. A presença de SN1/Agitação foi associada a volume de substância cinzenta reduzido em giro frontal médio direito (BA09-DLPFC); SN2/Hiperatividade com redução em giro temporal superior direito (BA22) e frontal inferior bilateral (BA47); e SN4/Psicose com redução em giro pré-central (BA44), temporal superior (BA22) e ínsula direitos em DA. No grupo CIND, somente SN1/Agitação evidenciou associação com redução de substância cinzenta regional. Atrofia de áreas corticais específicas parecem relacionadas aos sintomas e síndromes neuropsiquiátricos em DA. Síndromes neuropsiquiátricas em DA mostraram-se correlacionadas à atrofia de estruturas centrais de alguns circuitos neuronais envolvidos na fisiopatologia de transtornos psiquiátricos
The study of neuropsychiatric symptoms in patients with Alzheimer\'s disease (AD) by grouping these symptoms into syndromes has been increasingly used because it would detect differences in its prevalence and evolution, in relation to psychosocial determinants and neurobiological correlates. The aim of this study was to identify regions of reduced gray matter in cortical areas associated with specific neuropsychiatric symptoms and syndromes from the Neuropsychiatric Inventory (NPI) in patients with AD and cognitive impairment, no dementia (CIND). Voxel-based morphometry (VBM) plus Dartel (Diffeomorphic Anatomical Registration Exponentiated Using Lie Algebra) was used to verify the correlation between the presence of specific neuropsychiatric symptoms and syndromes and regional gray matter volume reduction throughout the brain and in regions predicted a priori. The syndromes were NS1/ Agitation (agitation, sleep and eating disorders), NS2/Hyperactivity (disinhibition, aberrant motor behavior and irritability), NS3/Affective (depression and apathy) and NS4/Psychosis (delusions and hallucinations). The presence of delusions was associated with gray matter volume reduction in right inferior frontal gyrus (BA45), depression with reduced gray matter in right inferior middle temporal gyrus (BA 37/22) and left inferior frontal gyrus (BA09-DLPFC) and left parahippocampal gyrus; anxiety with reduction in left middle frontal gyrus (BA10), and eating disorders with reduction in left anterior cingulate cortex (BA32) in patients with AD. The presence of NS1/Agitation was associated with gray matter volume reduction in the right middle frontal gyrus (BA09-DLPFC); NS2/ Hyperactivity with reduction in right superior temporal gyrus (BA22) and bilateral inferior frontal (BA47) and NS4/Psychosis with a reduction in right precentral gyrus (BA44), right superior temporal (BA22) and in right insula in AD. In the CIND group, only SN1/Agitation showed association with regional gray matter reduction. Atrophies of specific cortical areas were showed to be related to symptoms and neuropsychiatric syndromes in patients with AD

Health, social, and economic burden related to schizophrenia is significant for both patients and wider society (Knapp, 2000; Chong et al., 2016). Depression is common in people with schizophrenia (Whitehead et al., 2002) and is associated with particularly high levels of health care use (Steel et al., 2015). Developing and disseminating cost-effective interventions for people with depression in the context of psychosis is therefore indicated. The ADAPT trial was a pilot randomised controlled trial (RCT) of Acceptance and Commitment Therapy for depression after psychosis (ACTdp) for individuals with a diagnosis of schizophrenia who also met diagnostic criteria for major depression (Gumley et al., 2015; Gumley et al., 2017). A total of 29 participants were randomised to ACTdp+ Standard Care (SC) (n=15) or SC alone (n=14). The aim of the present study was to explore outcomes relating to cost-effectiveness of ACTdp and to consider the feasibility of conducting an economic evaluation alongside a larger, definitive trial. Cost-effectiveness was explored in a cost-utility analysis (CUA) with quality-adjusted life years (QALYs) as the primary outcome. QALYs were calculated from the EuroQol (EQ-5D-5L) and cost data were collected using the Client Service Receipt Inventory (CSRI). The incremental cost-effectiveness ratio (ICER) for ACTdp was £8,339 which falls below the assumed threshold of £20,000 per incremental QALY used by NICE (2012). A trend towards better outcomes and partial cost-offsets in the ACTdp group suggests that ACTdp may be a cost-effective treatment and that a larger, definitive trial to explore this further would be justified.

Introdução. O Transtorno Depressivo Maior (TDM) é um dos mais prevalentes e incapacitantes entre os transtornos mentais. Apesar disso, sua classificação ainda é baseada em sinais e sintomas, uma vez que suas causas e fisiopatologia ainda não foram totalmente esclarecidas. A presença de sintomas psicóticos é relativamente comum durante um episódio depressivo e está associada a particularidades clínicas e biológicas, mas é subdiagnosticada na prática clínica e os processos fisiopatológicos que caracterizam este tipo de depressão foram insuficientemente estudados, ainda mais ao se considerar a extensa literatura acerca das formas não psicóticas de depressão. O objetivo principal deste estudo foi o de investigar a neuroquímica do giro do cíngulo anterior (CA), região cerebral constituinte da neurocircuitaria relacionada à fisiopatologia do TDM, na forma psicótica deste transtorno. Para este objetivo, foram comparadas as concentrações absolutas dos metabólitos entre os grupos portadores de TDM com e sem sintomas psicóticos e controles saudáveis por meio de espectroscopia de próton por ressonância magnética de hidrogênio (1H-ERM). Secundariamente, analisou-se a interferência de variáveis sócio-demográficas e clínicas na medida desses metabólitos. Esperava-se que os pacientes com sintomas psicóticos (TDM-P) apresentassem alterações neuroquímicas tanto em relação ao grupo de controles saudáveis quanto a pacientes com depressão sem sintomas psicóticos (TDM-NP), independentemente da gravidade dos sintomas depressivos. Casuística e métodos. Os pacientes portadores de episódio depressivo maior (com e sem sintomas psicóticos), segundo o DSM-IV, foram recrutados no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP) e avaliados através da Entrevista Clínica Estruturada para o DSM-IV (SCID). A gravidade de sintomas depressivos e psicóticos, bem como o nível de funcionamento global foram avaliados por meio das escalas de Hamilton, BPRS e GAF (respectivamente). Foram coletadas informações a respeito de histórico de tentativas de suicídio, tratamento medicamentoso, comorbidades psiquiátricas e clínicas. Controles saudáveis da comunidade geral foram recrutados por convite da equipe de pesquisa. Utilizou-se 1H-ERM de voxel único, com tempo de eco (TE) curto (31ms), em campo magnético de 3 Tesla para a avaliação do CA de 20 pacientes com TDM-P, 22 com TDM-NP e 20 voluntários saudáveis. Foram analisados valores absolutos do glutamato (Glu), glutamato mais glutamina (Gln+Glu), N-acetilaspartato mais N-acetilaspartato-glutamato (NAA + NAAG), Fosforilcolina mais Glicerol-fosforilcolina (PC + GPC), mio-inositol (Myo) e Creatina (Cr). Dados sócio-demográficos e clínicos foram analisados através de ANOVA e qui-quadrado, enquanto os níveis de metabólitos foram comparados através de MANOVA. Correlações bivariadas entre dados clínicos e metabólitos foram analisadas por teste de Pearson ou Spearman. O nível de significância estatística empregado foi o de p <0,05. Resultados. Pacientes com TDM-P apresentaram menor escolaridade e pior funcionamento global, tanto em relação aos controles quanto em relação aos pacientes sem psicose. Os grupos de pacientes não diferiram entre si em relação à gravidade dos sintomas depressivos. Em relação aos metabólitos, houve diferença significativamente estatística entre os grupos diagnósticos. O grupo com TDM-P apresentou níveis de Glu inferiores tanto em relação ao grupo TDM-NP quanto ao grupo controle e níveis de PC + GPC e de NAA + NAAG inferiores ao grupo controle (a redução deste último metabólito atingindo significância estatística em nível de tendência apenas. Entre os sexos, os níveis de Glu e de NAA+NAAG dos participantes do sexo masculino foram inferiores aos do feminino. Por fim, os níveis de Glu e Gln+Glu foram inferiores no sexo masculino do TDM-P em relação aos demais grupos e os de Cr foram inferiores no sexo masculino no TDM-NP também em relação aos outros grupos. No entanto, as diferenças em relação ao sexo não atingiram significância estatística, possivelmente por limitações do tamanho amostral. Conclusão.Os níveis de metabólitos do CA sofreram interferência do diagnóstico e os resultados apontaram para efeito do sexo e da interação diagnóstico-sexo. As diferenças dos níveis de Glu, NAA+NAAG e PC+GPC entre os diagnósticos sugerem alterações de neurotransmissão glutamatérgica, metabolismo de membrana e integridade neuronal na TDM-P e corroboram os achados de outras áreas de estudo em depressão em psicose, que sugerem que a forma psicótica da depressão estaria mais associada ao estado de hipercortisolemia, e esta, por sua vez, levaria às alterações cerebrais compatíveis com as alterações encontradas no CA neste estudo. Além disso, os resultados apontam para a interferência do sexo nos níveis de Glu e NAA+NAAG, sugerindo um papel protetor dos hormônios femininos para o sistema glutamatérgico e ciclo do NAA. Ainda, este estudo não confirma hipóteses prévias de que as alterações biológicas entre os tipos de depressão seriam secundárias a maior gravidade de sintomas depressivos nos pacientes com TDM-P.
Introduction: Major depressive disorder (MDD) is one of the most prevalent and disabling of mental disorders. Nevertheless, its classification is still based on signs and symptoms, since its causes and pathophysyology has not been fully clarified. The presence of psychotic symptoms are relatively common during a depressive episode and is associated with clinical and biological peculiarities, but is underdiagnosed and its pathophysiology have been insufficiently studied, especially when considering the extensive literature on non-psychotic forms of depression. The aim of this study is to investigate the neurochemistry of the anterior cingulated gyrus (AC), a brain\'s neurocircuitry constituent related to the pathophysiology of MDD with psychosis/in the form of psychotic disorder. For this propose, we compared/ were compared the results of the metabolites between groups of patients with MDD with and without psychotic symptoms and controls by- proton resonance spectroscopy imaging of hydrogen (1rH-MRS). Secondly, the interference of socio-demographic and clinical on the cerebral metabolites. It was expected that patients with psychotic symptoms (MDD-P) present neurochemical changes in relation to the group of health controls and patients with depression without psychotic symptoms (MDD-Wo), regardless of the severity of depression symptons. Methods: The groups were diagnosed by the Structured Clinical Interview for DSM-IV (SCID). The severity of depressive and psychotic symptoms, as well as the level of overall functioning were assessed using the Hamilton Rating Scale, BPRS and GAF (respectively). We collected information about the history of suicide attempts, drug treatment, psychiatric and medical comorbidities.1\'H-MRS single voxel, with echo time (TE) short (3lms) in a magnetic field of 3.0 Tesla was used for the evaluation of CA in 20 patients with MDD-P, 22 with MDD-Wo and 20 healthy subjects. We analyzed the absolutevalues of glutamate (Glu), glutamate plus glutamine (Gln+Glu), N-acetylaspartate plus N-acetyl aspartate-glutamate (NAA+NAAG), glycerol phosphorylcholine plus phosphorylcholine plus choline (PC+GPC), myo-inositol (Myo) and creatine (Cr). Data on socio-demographic and clinical information were analyzed using ANOVA and chi-square, while the levels of metabolites were compared by MANOVA. The statistical significance level used was p <0.05. Results: Patients with MDD-P had less schooling and poorer overall functioning, both in relation to the controls as compared to patients without psychosis. Patient groups did not differ in the severity of depressive symptoms. Glu levels of MDD-P were lower than the MDD-Wo and the control group; NAA+NAAG levels of MDD-P were lower than in control and GPC+PC levels of MDDP were lower than the MDD-Wo. Between the sexes, Glu and NAA + NAAG levels of males were lower than females. Finally, Glu, Glu+Gln and Cr levels were different between the sexes within the groups. Conclusion:The group levels of metabolites of CA have been interfered with diagnosis and the effect of gender and gender-diagnosis interaction were close to be meaningful. The differences in the levels of Glu, NAA + NAAG and GPC + PC between diagnoses are possibly related to higher hypercortisolemia found in the MDD-P and the brain concentration of kynurenine metabolites imballance more similar with schizophrenia than MDD. The interference of sex for the levels of Glu and NAA + NAAG suggests a protective role of female hormones to glutamatergic system and cycle of the NAA. Still, probably the severity of the depressive episodes not implicated in the neurochemical differences between MDD-P and MDD-Wo

The symptoms, classification, occurrence and possible aetiologies of bipolar manic-depressive psychosis have been reviewed, with particular emphasis on the possible role of the vanadate ion (V5+) and cation transport in the illness. The effect of vanadate on cation transport in intact cells has been determined using the well-characterised HeLa cell line. Cation transport in virally transformed lymphoblastoid cell lines from 13 bipolar manic-depressive patients and 13 control subjects has been examined, under normal conditions and after treatment (24 hours) with lithium, ouabain or vanadate. The phosphatidylinositol system has also been examined in these cell lines, in view of the therapeutic effect of lithium, and its known inhibitory actions on inositol I-phosphatase. In HeLa cells, no effects of vanadate on cation transport were seen until concentrations greater than 3.2 x 10- 6 M. This was attributed to the intracellular reduction of V5+ to V4+ shown to occur using ESR. Similar decreases were seen in all the K+ influx pathways, with maximum decreases of approximately 30% at 10-4M vanadate extracellularly. Significant toxicity was also seen at these concentrations, with a maximum decrease in cell number of 40% at 10-4M vanadate. No change in the energy charge was seen and changes in ATP levels occurred subsequently to the changes in cell number, with a decrease of 40% at 10-4M vanadate. Using the lymphoblastoid cell lines, no significant differences were seen in any of the cation transport parameters examined, with the exception of mean sodium pump number which was 30% greater in the bipolar group compared with the control group. Lithium or vanadate treatment produced either no effect or inconsistent changes in cation transport. Ouabain treatment produced similar decreases in sodium pump number in both groups. Inositol uptake was similar in both groups, but the percentage incorporation into phosphoinositides was reduced in bipolar cell lines compared with controls.

Dans la littérature scientifique actuelle, des études ont mis en évidence par une approche transdiagnostique, l’implication de facteurs cliniques, biologiques et génétiques spécifiques des conduites suicidaires indépendamment d’un diagnostic de trouble psychiatrique de l’Axe I ou II du Manuel Diagnostique et Statistique des Troubles Mentaux (DSM) (1–3). De plus, l’existence d’un trouble psychiatrique n’apparaît pas être discriminante pour définir certains types de profils de patients à risque de suicide (4–6). En effet, le suicide peut toucher à la fois des personnes dites en situation de crise mais il est largement reconnu que les pathologies psychiatriques restent à haut risque de suicide, notamment les troubles de l’humeur tels que les troubles bipolaires et les dépressions unipolaires, et plus particulièrement avec caractéristiques psychotiques (7,8). De plus, des facteurs de risque spécifiques de suicide ont été retrouvés dans chacune de ces différentes populations (9,10). Ainsi, avec cette conception moderne du suicide, il semble pertinent d’étudier le risque suicidaire dans diverses populations de suicidants, souffrant ou non de troubles psychiatriques, et en utilisant une approche tant épidémiologique, dynamique avec l’actigraphie, et biologique (3,11,12). En me basant sur cette approche, mon projet de thèse s’articule en 3 axes décrits ci-après, et consiste à identifier des facteurs de risque de récidive de tentative de suicide ainsi qu’à définir des profils de patients suicidants dans des populations différentes. Pour cela, plusieurs études coordonnées permettront de réaliser une évaluation multi-échelles de la vulnérabilité suicidaire de façon transdiagnostique et de façon ciblée dans les troubles de l’humeur uni- et bi-polaires
In the current scientific literature, the studies have been highlighted by a transdiagnostic approach, implementation of clinical, biological and genetic factors, suicidal behavior independent of a diagnosis of psychiatric disorder in Axis I or II of the Diagnostic and Statistical Manual. Mental Disorders (DSM) (1-3). In addition, the endurance of psychiatric disorder is not discriminating to define certain types of profiles of patients at risk of suicide (4-6). In fact, suicide can affect both people in crisis but it is widely recognized that psychiatric pathologies remain at high risk of suicide, including mood disorders such as bipolar disorder and unipolar depression, and especially with psychotics (7,8). In addition, specific suicide risk factors were found in these different populations (9,10). Thus, with this modern conception of suicide, it seems relevant to study suicidal risk in various suicidal populations, with or without psychiatric problems, and using an epidemiological approach, dynamic with actigraphy, and biological (3, 11 , 12).For this, there are several different assessments of vulnerability of suicide in a transdiagnostic and targeted way in the problems of the united and bi-polar moods

Old people in general, and those affected by dementia disorders in particular, are more sensitive to drug side effects than younger people. Despite this, the use of nervous system drugs and analgesics among old people is common, and has increased in recent years. Institutional geriatric care accommodates people who need round-the-clock supervision and care, due to somatic, psychiatric, cognitive or behavioral symptomatology. A majority of those living in institutional geriatric care suffers from dementia disorders. This thesis is based on three different data collections. Two large cross-sectional studies, the AC1982 and AC2000 data collections, including all those living in institutional geriatric care in the county of Västerbotten in May 1982 and 2000 respectively (n=3195 and n=3669) and one study, the GERDA/Umeå 85+ data collection, including a sample of very old people, living at home and in institutions (n=546), in the municipalities of Umeå, Sweden and Vaasa and Mustasaari, Finland, in 2005-2006. The use of psychotropic drugs and analgesics was common among old people living in geriatric care and among very old people in general. A higher proportion of people with dementia received certain nervous system drugs, such as antipsychotic drugs. The use of antipsychotic drugs among people with cognitive impairment living in geriatric care was found to be correlated to several behaviors and symptoms that are not proper indications for antipsychotic drug use, and also factors related more to the staff and the caring situation. Over the course of eighteen years, from 1982 to 2000, there has been a manifold increase in the use of antidepressants, anxiolytics and hypnotics in geriatric care, but the use of antipsychotics had decreased slightly. During the same time, the prevalence of several depressive symptoms decreased significantly, correcting for demographical changes. One analysis of calculated numbers needed to treat, however, indicated poor remission rates, suggesting that even better results might be achievable. The prevalence of depressive symptoms among people with moderate cognitive impairment remained unchanged between 1982 and 2000, despite the fact that about 50% were receiving treatment with antidepressants in 2000. One possible explanation might be that depressive symptoms have different etiologies in different stages of a dementia disorder. Approximately a quarter of the people experiencing pain in geriatric care were not receiving any regular analgesic treatment. One possible reason might be misconceptions among the caring staff regarding whether or not the residents were receiving analgesic treatment. Such misconceptions were found to be common. In conclusion, psychotropic and analgesic drug use among old people in geriatric care, and very old people in general, was found to be common and in many cases possibly inappropriate. The use of antipsychotics among people with dementia deserves particular concern, because of the high risk of severe adverse events and the limited evidence for positive effects. The use of antidepressants, on the other hand, might have contributed to a lower prevalence of depressive symptoms among old people.

L'estrès i el dol associats a la migració, així com la manca d'equitat en l'accés als serveis sanitaris influeixen negativament en la salut mental. Aquesta tesi té com objectiu determinar si l'exposició i l'adherència a antidepressius i antipsicòtics és diferent entre autòctons i immigrants d'una regió espanyola. S'han realitzat quatre estudis entre 2007 i 2009 a partir de les dispensacions de fàrmacs a la població de la regió. Tots els grups immigrants reben menys antidepressius i antipsicòtics que la població autòctona d'igual edat i sexe, amb diferències entre grups. El risc relatiu d'abandonament dels antidepressius és un 28% major en els immigrants; el 36,8% abandona el primer mes i només el 29,5% manté una bona adherència, davant el 38,8% dels autòctons. L'adherència als antipsicòtics és bona en el 19,1% dels immigrants i el 40,4% dels autòctons. Les diferències trobades indiquen la necessitat d'aprofundir en les causes per establir les polítiques d'actuació necessàries.
El estrés y el duelo asociados a la migración y la falta de equidad en el acceso a los servicios sanitarios influyen negativamente en la salud mental. El objetivo de esta tesis es determinar si la exposición a antidepresivos y antipsicóticos es diferente entre inmigrantes y autóctonos de una región española. Se realizaron cuatro estudios entre 2007 y 2009 a partir de las dispensaciones de fármacos. Todos los grupos inmigrantes recibieron menos antidepresivos y antipsicóticos que la población autóctona de igual edad y sexo, con diferencias entre grupos. El riesgo relativo de abandono de los antidepresivos fue un 28% mayor en los inmigrantes; el 36,8% abandonó durante el primer mes y solo el 29,5% mantuvo una buena adherencia, frente al 38,8% de autóctonos. La adherencia a antipsicóticos fue del 19,1% y 40,4% para inmigrantes y autóctonos respectivamente. Las diferencias encontradas indican la necesidad de profundizar en las causas para establecer las políticas de actuación adecuadas.
Immigration is a stressful process and a risk factor for mental illness. Inequality in health care access can worsen this situation. The aim of this study is to determine if there are differences between immigrants and non-immigrants in the use of and compliance with antidepressant and antipsychotic treatment in a Spanish region. It includes four studies on pharmaceutical dispensing done between 2007 and 2009. All immigrant groups have lower antidepressant and antipsychotic consumption than the native population of the same age and sex, with differences between groups. The relative risk of abandoning treatment is 28% higher in immigrants; 36,8% filled only one prescription and 29,5% presented good compliance compared with 38,8% of natives. Antipsychotic adherence was appropriate for 19,1% of immigrants and 40,4% of native. More research is needed to understand the causes of these differences and to ensure adequate access and use of mental health services.

This study represents an attempt to describe the extent and features of safe haven legislation in the United States, discuss implementation issues, and to examine if the legislation is reaching its intended target audience in order to answer the question, "Is safe haven legislation an efficacious response to infant abandonment?" Safe havens are designated locations where infants can be anonymously abandoned without fear of prosecution or incarceration. As of May of 2006, forty-seven states have passed such legislation, citing the need for an alternative to unsafe infant abandonment leading to an infant's death, and an alternative to infanticide (the killing of an infant within one year of its birth). Since the initial passage of this legislation in Texas in 1999, there have been more unsafe infant abandonments than accounts of safe haven abandonments. As this legislation provides for anonymous infant abandonment researchers cannot study the population of women actually utilizing safe havens. Therefore, the study of women seeking connection with safe havens in comparison to the population of women who have engaged in infant abandonment resulting in an infant's death is considered one of the sole viable sources of insight into this problem. The scope of the research is exploratory in nature and analyses are considered preliminary due to the lack of data that exists in this area and the relative newness of the legislation.A quantitative analysis of women likely to utilize safe havens reveals that they have a mean age of 19, are unmarried, have entered into prenatal care late, have disclosed their pregnancy to someone, and are currently dating the birthfather. The findings from this analysis were compared to those from a national linked birth and infant death dataset to ascertain if women seeking safe havens have similar biopsychosocial characteristics as those engaging in unsafe abandonment leading to an infant's death. Similar biopsychosocial characteristics were found including mother's age, marital status, late entry into prenatal care, disclosure of pregnancy, and dating status. A regression analysis was used to construct a biopsychosocial profile of women likely to abandon an infant. Findings suggest that legislators and those involved with safe havens have some knowledge of their target population, but are not effectively reaching this audience, nor promoting the existence of safe havens. They also appear to be utilizing research findings on infanticide inappropriately, in order to profile their target audience. This effectively limits the promulgation of education and early identification services that could prevent both safe haven and unsafe infant abandonments. This study concludes with policy reform recommendations.

Abstract Maternal depressed mood during pregnancy is common, but studies on the offspring of antenatally depressed mothers, with a long follow-up, are scarce. The aim was to study whether the adult offspring of antenatally depressed mothers are at an elevated risk of psychoses, depression, bipolar disorder, antisocial and borderline personality disorder, and schizotypal and affective traits. Parental severe mental disorder was considered as both a genetic and environmental risk factor for mental disorders. The data are based on the unselected, prospective, population-based Northern Finland 1966 Birth Cohort of 12,058 live-born children. The data were collected beginning from pregnancy and ending mid-adulthood. The mothers were asked about their mood during pregnancy at the antenatal clinic at 24–28 gestational weeks. Of the mothers, 13.9% rated themselves as depressed (11.8%) or very depressed (2.1%) during pregnancy. Parents’ severe, hospital-treated mental disorders, and the cohort members’ mental disorders were identified mainly by using the Finnish Care Register for Health Care. In this study, the adult offspring of antenatally depressed mothers had an increased risk of depression, and the male offspring for antisocial personality disorder, compared to cohort members without antenatally depressed mothers. The offspring with both maternal antenatal depressed mood and parental severe mental disorder had a markedly elevated risk of schizophrenia and depression, compared to cohort members without one or both of the risk factors. This is the first study where the offspring of antenatally depressed mothers were followed till mid-adulthood, also taking into account parental severe mental disorders. Based on the findings, the prevention of and early intervention in antenatal depression, especially in families with severe mental illness, might present an opportunity to reduce the risk of mental disorders in the offspring
Tiivistelmä Äitien raskausajan masennus on yleistä, mutta pitkiä seurantatutkimuksia raskausaikana masentuneiden äitien lapsista on vähän. Tutkimuksen tavoitteena oli selvittää, onko raskausaikana masentuneiden äitien aikuisilla jälkeläisillä kohonnut riski sairastua skitsofreniaan, masennukseen, kaksisuuntaiseen mielialahäiriöön, epäsosiaaliseen tai epävakaaseen persoonallisuushäiriöön, ja ilmeneekö heillä enemmän skitsotyyppisiä tai affektiivisia piirteitä. Vanhempien vakavien mielenterveydenhäiriöiden katsottiin olevan sekä mahdollisia geneettisiä että ympäristöön liittyviä riskitekijöitä jälkeläisten mielenterveyshäiriöille. Tutkimus perustuu yleisväestöön pohjautuvaan, prospektiiviseen Pohjois-Suomen vuoden 1966 syntymäkohorttiin, johon kuuluu 12 058 elävänä syntynyttä lasta. Kohortin jäseniä on seurattu sikiöajalta keski-ikään, aina 49 ikävuoteen saakka. Äitien raskaudenaikaista mielialaa tiedusteltiin raskausviikoilla 24–28 neuvolassa. 13,9 % äideistä raportoi mielialansa masentuneeksi (11,8 %) tai hyvin masentuneeksi (2.1%) raskausaikana. Vanhempien vakavat mielenterveydenhäiriöt ja kohortin jäsenten mielenterveyshäiriöt selvitettiin pääosin hoitoilmoitusrekisteritiedoista. Tutkimuksessa raskaudenaikana masentuneiden äitien lapsilla havaittiin kohonnut depressioriski sekä kohonnut epäsosiaalisen persoonallisuushäiriön riski miehillä, verrattuna kohortin jäseniin, joiden äitien mieliala ei ollut masentunut raskausaikana. Kohortin jäsenillä, joiden äideillä oli raskausajan masennusta ja toisella vanhemmista vakava mielenterveyshäiriö, oli kohonnut riski sairastua skitsofreniaan ja depressioon, verrattuna heihin, joilla oli vain yksi tai ei kumpaakaan näistä riskitekijöistä. Tämä on ensimmäinen tutkimus, jossa raskausaikana masentuneiden äitien lapsia on seurattu keski-ikään saakka, huomioiden myös vanhempien vakavat mielenterveydenhäiriöt. Tutkimuksen tulosten perusteella äidin raskausajan masennusoireiden varhaisen tunnistamisen ja hoidon voitaisiin ajatella vähentävien jälkeläisten mielenterveysongelmien riskiä, etenkin perheissä, joissa on vakavia mielenterveysongelmia

Research Doctorate - Doctor of Philosphy (PhD)
A large body of population- and treatment-based evidence exists to indicate depression and alcohol/other drug (AOD) use are highly prevalent on a global scale, and co-occur with considerable frequency. Despite this evidence, significant gaps exist in treatment research and clinical services, as people with co-occurring depression and AOD use problems have typically been excluded from randomised controlled treatment trials, and also face many individual- and service-level barriers to accessing treatment. Consequently, a well-defined and adequately tested treatment strategy does not currently exist for people experiencing the complexities of concurrent depression and AOD use problems. A small body of evidence exists to suggest that co-occurring mental and AOD use disorders (“comorbidity”) leads to poorer treatment outcomes, increased risk of relapse, higher levels of problematic symptomatology, and poorer quality of life. However, little consistent information is currently available to suggest what additional impact comorbid depression and AOD misuse produces relative to the experience of a “single” condition (such as depression or AOD misuse in isolation). Studies 1 and 2 attempted to address this important gap in knowledge by examining the presenting characteristics of 246 people with AOD use problems, according to the presence of comorbid depressive symptoms. One hundred and thirty seven participants were drawn from AOD treatment services, and a further 109 were referred via mental health services and also met criteria for a psychotic disorder. Results indicated that the presence of depression was associated with a significantly higher severity of psychiatric symptoms and personality disorder, significantly decreased social and occupational functioning and significantly reduced quality of life. Current depression was also associated with a significant increase in the experience of cravings and self-reported dependence on amphetamines. These difficulties were over and above the already high rates of disability and distress reported by each sample as a whole. Furthermore, treatment for mental health problems was rare among the AOD treatment participants, as was AOD treatment among the mental health sample. This is despite the presence of moderate to severe levels of depression and AOD use reported by each sample. In particular, Studies 1 and 2 highlight the vulnerabilities for people with comorbid mental health and AOD use problems who present to treatment in the mental health or AOD use settings, and in particular how depression significantly increases the disability and other challenges experienced by these people. These results provide a strong rationale for the development of an appropriate treatment protocol for depression and AOD use comorbidity. No clear treatment model or evidence-based approach exists to suggest how depression and AOD use comorbidity is best managed. When people with this comorbidity do manage to access clinical treatment services, they typically receive treatment targeted at one aspect of their presentation (e.g. depression-focussed or AOD-focussed treatment). Yet, it is not known whether a singular focus of treatment is effective in producing sustainable change in the outcomes of people with comorbid problems, nor whether failure to treat all components of the comorbid presentation confers a worse outcome. Studies 3 and 4 reported on two randomised controlled clinical trials of psychologicaltreatment for AOD use problems among a sample of 246 people with AOD use problems, drawn from AOD treatment services (n=137) or mental health services (n=109). In doing so, these studies provide some of the first available data on these issues. Participants were categorised according to the presence of comorbid depression (as per Studies 1 and 2) and response to treatment was analysed over a six- to 12-month follow-up period. In spite of high levels of current depressive symptoms at entry to the studies, and equally hazardous use thresholds of a range of substance, people enrolled in Studies 3 and 4 reported some gains via their experiences with these single-focussed treatments. Attendance and retention rates were higher than reported in previous research, and the presence of depression did not adversely influence the motivation of project participants to change their current AOD use patterns. A treatment effect was generally not detected among the Study 3 and 4 participants, regardless of the presence of depression, with those receiving an assessment-only control treatment in both studies reporting similar patterns of change in outcome. Regardless of the magnitude of change reported by all study participants, people with depression reported significantly higher levels of depression, poly-drug use, amphetamine dependence, hazardous use of a range of substances, HIV risk taking and criminal activity and lower levels of functioning and self-concept across the follow-up assessment period. These residual symptoms were present at sufficiently high levels of severity to increase the risk of relapse to AOD use and continued morbidity. These results suggested the potential value of targeting depression in the context of comorbid AOD use problems. One previous study has examined the impact of an adjunctive psychological treatment of depression for people hospitalised for alcohol use disorder. Results indicated that people who received the additional depression treatment reported significantly greater improvements on depression- and alcohol-related outcomes over the short-term relative to people receiving a relaxation-only control treatment. These improvements were suggested to be enhanced if treatment had integrated depression- and alcohol-related approaches into the one treatment program. In the first study of its kind, Study 5 developed and evaluated the efficacy of an integrated psychological treatment program for comorbid depression and AOD use problems. Sixty-seven participants received integrated treatment delivered by a therapist, computer-delivered integrated treatment or a brief intervention (control) treatment delivered by a therapist. Depression scores, daily use of alcohol and cannabis, hazardous use of a range of substance and poly-drug use fell significantly over a 12-month follow-up period across the integrated treatments and brief intervention (control) conditions. The small sample size of Study 5 meant that very few treatment effects were detected at a statistically significant level, however important reductions in key outcomes for depression, AOD use, quality of life and general functioning were noted for people in the integrated treatment relative to controls over a 12-month period. The magnitude of change in Study 5 across these domains was comparable with the only other study of psychological treatment of depression and alcohol-use disorders described above. The integrated treatment in Study 5 was associated with higher levels of improvement in depression, alcohol use and cannabis use (where present) than did the AOD-focussed treatment examined in Studies 3 and 4. The results further suggest that a brief intervention targeting both depression and AOD drug use problems is associated with reductions in key outcomes in the short-term, withintegrated, lengthier psychological treatment potentially associated with longer-term changes on the same outcomes. No previous study has directly compared the outcomes for people completing psychological treatment delivered via a computer program with those completing treatment with a ‘live’ clinician over an extended follow-up period of 12-months. Given the barriers people with comorbid depression and AOD use problems face in accessing available treatment services, the consideration of alternative modes of delivery of evidence-based treatment to this group is timely. Study 6 expanded on the Study 5 results by presenting further analysis of the performance of the computer-delivered version of the integrated treatment relative to the clinician-delivered equivalent, matched for content. Given the small sample size of participants, Study 6 devised a four-point criterion which, if satisfied, would suggest that the computer-delivered and clinician-delivered integrated treatments were approximately equal. Based on these criteria, the results indicated that the outcome profiles for people engaged in the computer-delivered treatment were equivalent to those reported by people involved in clinician-delivered therapy over a 12¬month follow-up period. Additionally, computer-delivered integrated treatment was associated with similar rates of improvement as the therapist-equivalent on depression scores, risky drinking patterns, hazardous use of substances, poly-drug use, levels of daily cannabis use, suicidality, treatment retention and therapeutic alliance. This result requires further replication to test these assumptions, however it is promising that a treatment requiring an average of 12-minutes face-to-face of “generic” clinician time per weekproduces a similar pattern of improvement to a treatment requiring an average of 60 minutes of face-to-face specialist psychologist input over the same time period. Studies 1-6 resulted in the development of a menu of treatment options for people with depression and AOD use comorbidity, with each treatment approach providing evidence for at least some benefit among the study participants. While encouraging, these results again raise the issue of how treatment may be incorporated into existing services (mental health, AOD use, primary care, etc.), which typically remain segregated, with little opportunity for collaboration and cross-fertilisation of skills and expertise between service settings. Chapter 7 discusses a new model of treatment for comorbid depression and AOD use problems that incorporates the results of Studies 1-6, and involves a stepped care approach to developing a treatment plan tailored to the specific needs and levels of distress experienced by people with depression and AOD use comorbidity. The stepped care model of treatment could be incorporated into existing service settings and structures, with the potential for computer-based therapy to provide access to specialised treatment for depression and AOD use comorbidity that might otherwise be unavailable. As a result, stepped care treatment could foster earlier engagement with treatment services and encourage motivation and optimism among people with comorbid depression and AOD use problems. These are important issues for service development and delivery of appropriate treatments to this underserved population.

Dissertação de mestrado em Ciências da Saúde
Electroconvulsive therapy (ECT) continues to be considered an effective treatment of psychotic patients with hallucinatory and delusional symptoms resistant to antipsychotic medication. Several studies have evaluated the effectiveness of ECT in major depression as well as the effect of cortisol in the evolution and prognosis of those patients. However, studies that evaluate the evolution of the delusional and hallucinatory schizophrenic patients, psychotic depression and schizoaffective psychotic patients treated with ECT and its correlation with the salivary cortisol are scarce. Moreover, stress plays a significant role in modulation of mental disorders, and the hypothalamic-pituitary-adrenal (HPA) axis regulates the biological mechanisms of stress. In this project we have assessed the clinical evolution of patients in three diagnostic groups, namely patients psychotic depression, schizoaffective disorder and schizophrenia before and after ECT. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychotic symptoms, the Perceived Stress scale (PSS) to evaluate perceived stress, the Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and depression and salivary cortisol levels to evaluate the HPA axis function. The results of our study demonstrate that ECT is effective and a valuable therapeutic option which could be useful as adjunctive therapy in psychotic patients refractory to antipsychotics agents. There was a noticeable improvement in the PANSS, HADS and PSS scores after ECT in all psychotic patients in our study. Moreover, this study shows the effectiveness of ECT in chronic psychotic patients, while most studies have studied first psychotic episodes. The decrease of salivary cortisol after ECT in our study suggests that it may impact in the HPA axis, improving its function. However, the mechanism by which it can improve HPA axis function remains unclear. Finally, the correlations between variables revealed that the HADS score may predict the rate of response to ECT. In conclusion, the present study has confirmed the role of ECT in the treatment of psychotic disorders. Importantly, a relation between HPA axis function and ECT was revealed specifically in patients with schizophrenia and psychotic depression but not in schizoaffective disorder, suggesting a distinct involvement of this key neurobiological factor.
A eletroconvulsoterapia (ECT) continua a ser considerada um tratamento eficaz para pacientes psicóticos com sintomatologia delirante e alucinatória resistente à medicação antipsicótica. Vários estudos têm avaliado a eficácia da ECT na depressão major, bem como o efeito do cortisol na evolução e prognóstico desses pacientes. No entanto, estudos que avaliam a evolução em pacientes com esquizofrenia , depressão psicótica e psicose esquizoafetiva tratados com ECT e sua correlação com o cortisol salivar são escassos. Além disso, o stress desempenha um papel significativo na modulação de perturbações mentais sendo regulado pelo eixo hipotálamohipófise- adrenal (HPA).Neste projeto, avaliamos a evolução clínica dos pacientes em três grupos diagnósticos, nomeadamente pacientes com depressão psicótica, perturbação esquizoafetiva e esquizofrenia, antes e depois da ECT. A escala de sintomas positivos e negativos (PANSS) foi utilizada para avaliar sintomas psicóticos, a escala de stress percebido (PSS) para avaliar a percepção de stress, a escala de ansiedade e depressão hospitalar (HADS) para avaliar a ansiedade e a depressão e os níveis de cortisol salivar para avaliar a função do eixo HPA. Os resultados do nosso estudo demonstram que a ECT é eficaz e uma valiosa opção terapêutica que pode ser útil como terapia adjuvante em pacientes psicóticos refratários a agentes antipsicóticos. Observou-se uma melhoria significativa nas pontuações PANSS, HADS e PSS após ECT em todos os grupos de pacientes psicóticos no nosso estudo. Além disso, este estudo demonstrou a eficácia da ECT em pacientes psicóticos crónicos, enquanto a maioria dos trabalhos têm estudado primeiros episódios psicóticos. A diminuição do cortisol salivar após ECT no nosso estudo sugere que esta tem um impacto sobre o eixo HPA, melhorando a sua função. No entanto, o mecanismo pelo qual ela modula a função do eixo HPA permanece desconhecido. Finalmente, as correlações entre as variáveis revelaram que os niveis de HADS podem predizer a taxa de resposta à ECT. Em conclusão, o presente estudo confirmou o papel da ECT no tratamento de perturbações psicóticas. De realçar, a relação entre a função do eixo HPA e ECT foi revelada especificamente em pacientes com esquizofrenia e depressão psicótica, mas não na perturbação esquizoafetiva, sugerindo um envolvimento distinto deste factor neurobiológico.

碩士
高雄醫學大學
醫學研究所
97
Metabolic syndrome is a serious side effect of many atypical antipsychotic medications, yet successful strategies for significant weight loss are lacking. The purpose of this study was to assess the effects of exercise intervention on body composition, blood lipid profile, psychotic symptoms and depression status in schizophrenia with clozapine-therapy. Thirty-three schizophrenia patients with clozapine-therapy over 3 months in Yuli-hospital were included (Body Mass Index＞24 Kg/㎡, age＜60 yrs). They are divided into exercise and control group. Twenty-eight patients (14 in control and 14 in exercise group) finished the program. The exercise program is stepper training 30-60 minutes per section, 3 sections a week, total 12 weeks. Pre-test data reveal that male patient had better satisfaction on body figure than female; the prevalence of metabolic syndrome and depression disorder are higher than common population. After exercise intervention, exercise group had significant improvement on BMI, hip circumference, waist circumference or the items of sleeping behavior change and loss of sexual interesting in the Beck Depression Inventory-Second Edition. Compared with control group, the exercise group shows improvement on body weight, BMI, waist circumference, body fat, depression and suspiciousness in Brief Psychiatric Rating Scale. However the blood biochemical laboratory data did not had significant difference after training. The exercise duration reveals negative moderate correlation with Waist-Hip-Ratio change and positive moderate correlation with high density lipoprotein change. There is positive moderate correlation between the change of snacks times per day and low density lipoprotein change. According the result, we conclude that: The 12-week exercise training program contributes to the improvement of body composition, psychotic symptoms, and severity of depression. The amount and duration of exercise, diet amount reveal moderate correlation with body composition and some items of blood biochemical value. But the exercise intervention reveals no significant effect on blood biochemical value. For further study, we suggest increasing the sample’s diversity, random grouping, and excluding the patient with diabetes mellitus or hyperlipidemia history to lower the study bios. Additionally, we also suggest prolonging the exercise duration and follow-up period for more definitive result.

The management of acute psychosis is a constant challenge to the health care system, with only a limited amount of research providing data for allied health care practitioners. Despite anecdotal data indicating that music therapy may be an effective intervention, there have been few studies to date which provide any rigorous empirical evidence. This project aimed to test several hypotheses. The study has shown that music therapy is a valuable therapeutic adjunct to standard ward programs for the management of an acute psychotic episode resulting in shorter hospital stays, considerable cost savings and significant improvement in symptomatology as judged by the standardized measures employed. In addition, EFG testing while listening to self-chosen music demonstrated a reduction in dysfunctional brain wave activity. This project has highlighted the importance of music therapy in allied mental health care and opens up the need for further research into the management of such a large disease burden in Australia.
Doctor of Philosophy (PhD)

碩士
長庚大學
護理學研究所
84
The purpose of this study was to find out the relationships among personal attributes, locus of control, lithium attitudes, social support, coping behaviors, and lithium compliance in manic-depressive psychotic outpatients. Promin Subjects were selected by purposive sampling from the MDP outpatients who were treated with lithium for more than one year in an Adult Psychiatric Clinic of Taipei City Psychiatric Center. One The study results revealed : 1. The number of case compliance: Of all cases,41 outpatients''s behaviors were conformable to the standards of patient''s self- report, chart review, and lithium serum level. In patient''s self-report, 69 outpatients were compliant. In chart review, 84 out 2.Correlation: Sex, time period of taking lithium, and social class are significant correlative to lithium compliance."Powerful locus of control" is conformable to lithium compliance stan 3.Analysis of prominent variables which affect lithium compliance: (1)Lithium compliance conformable to patient''s self-report, chart review, and lithium serum level as dependant variables :To one whose locus of control is inclined to "powerful locus of control," the lithium compliance is 0.86 times over one with other (2)The compliance in keeping with patient''s self-report as dependant variables : To one who highly worries about "secondary stress," the lithium compliance is 0.94 times over others. (3)The compliance in keeping with chart review as dependant variables : To one whose attitude of "prepared action" is nice, his/her lithium compliance is 1.25 times over one with poor attitude. To one who responds to secondery stress "free and easy," th