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Euba, O., E. Zallo, M. Torreblanca, A. Arroita, N. Sánchez, and A. Barreiro. "Postraumatic Psychosis. Clinical Features." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)71146-0.
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Aims:Traumatic brain injury (TBI) cause a wide range of after-effects, including psychiatric disorders. Psychosis although uncommon is a very serious consequences with important functional, therapeutical and legal implications.Methods:Our work is based on a systemic review of the articles published related to TBI and psychosis.Results and conclusions:Delirious psychosis are twice more common than schizophrenia-like psychosis (28% to 14%).Delusions and hallucinations are predominant over passive phenomena or negative symptoms.Evolution and chronicity of postraumatic psychosis depends on the severity of the TBI and on the psychiatric and neurological previous conditions.Treatment is the same as used for typical psychosis, even though side effects are more frequent.
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van Amsterdam, Jan, Tibor Brunt, and Wim van den Brink. "The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects." Journal of Psychopharmacology 29, no. 3 (January 13, 2015): 254–63. http://dx.doi.org/10.1177/0269881114565142.
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Meyhöfer, Inga, Veena Kumari, Antje Hill, Nadine Petrovsky, and Ulrich Ettinger. "Sleep deprivation as an experimental model system for psychosis: Effects on smooth pursuit, prosaccades, and antisaccades." Journal of Psychopharmacology 31, no. 4 (November 11, 2016): 418–33. http://dx.doi.org/10.1177/0269881116675511.
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Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs.
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Barkus, E., and S. Lewis. "Schizotypy and psychosis-like experiences from recreational cannabis in a non-clinical sample." Psychological Medicine 38, no. 9 (January 21, 2008): 1267–76. http://dx.doi.org/10.1017/s0033291707002619.
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BackgroundThe relationship between cannabis use and psychosis is still a matter for debate. Accounting for the individual differences in subjective experiences to recreational cannabis use in the general population may hold some clues to the aetiological relationship between cannabis and psychotic symptoms. We hypothesized that schizotypy would account for the individual differences in subjective experiences after cannabis use but not in patterns of use.MethodIn a sample of 532 young people who had used cannabis at least once, we examined the relationship between the Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ). Additionally, we examined the psychometric properties of the CEQ.ResultsWe replicated our previously reported findings that schizotypy was associated with increased psychosis-like experiences and after-effects, but also found that high-scoring schizotypes reported more pleasurable experiences when smoking cannabis. Using new subscales derived from principal components analysis (PCA), we found that the psychosis-like items were most related to varying rates of schizotypy both during the immediate use of cannabis and in the after-effects of cannabis use. High-scoring schizotypes who used cannabis experienced more psychosis-like symptoms during and after use.ConclusionsOur results suggest that cannabis use may reveal an underlying vulnerability to psychosis in those with high schizotypal traits.
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Taylor, Hannah E., Suzanne L. K. Stewart, Graham Dunn, Sophie Parker, David Fowler, and Anthony P. Morrison. "Core Schemas across the Continuum of Psychosis: A Comparison of Clinical and Non-Clinical Groups." Behavioural and Cognitive Psychotherapy 42, no. 6 (August 7, 2013): 718–30. http://dx.doi.org/10.1017/s1352465813000593.
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Background: Research suggests that core schemas are important in both the development and maintenance of psychosis. Aims: The aim of the study was to investigate and compare core schemas in four groups along the continuum of psychosis and examine the relationships between schemas and positive psychotic symptomatology. Method: A measure of core schemas was distributed to 20 individuals experiencing first-episode psychosis (FEP), 113 individuals with “at risk mental states” (ARMS), 28 participants forming a help-seeking clinical group (HSC), and 30 non-help-seeking individuals who endorse some psychotic-like experiences (NH). Results: The clinical groups scored significantly higher than the NH group for negative beliefs about self and about others. No significant effects of group on positive beliefs about others were found. For positive beliefs about the self, the NH group scored significantly higher than the clinical groups. Furthermore, negative beliefs about self and others were related to positive psychotic symptomatology and to distress related to those experiences. Conclusions: Negative evaluations of the self and others appear to be characteristic of the appraisals of people seeking help for psychosis and psychosis-like experiences. The results support the literature that suggests that self-esteem should be a target for intervention. Future research would benefit from including comparison groups of people experiencing chronic psychosis and people who do not have any psychotic-like experiences.
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Solmaz, Volkan, Dursun Delibas, Sema Inanir, and Oytun Erbas. "Antipsychotic like effects of atorvastatin and melatonin in a psychosis model in rats." Journal of Mood Disorders 5, no. 3 (2015): 120. http://dx.doi.org/10.5455/jmood.20150714014531.
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Shin, E. J., J. M. Kim, X. K. T. Nguyen, T. T. L. Nguyen, S. Y. Lee, J. H. Jung, M. J. Kim, et al. "Effects of Gastrodia Elata Bl on Phencyclidine-Induced Schizophrenia-Like Psychosis in Mice." Current Neuropharmacology 9, no. 1 (March 1, 2011): 247–50. http://dx.doi.org/10.2174/157015911795017263.
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Bersani, Giuseppe, Pietropaolo Marino, Giuseppe Valeriani, Valentina Cuoco, Claudia Zitelli, Claudia Melcore, and Francesco Saverio Bersani. "Manic-Like Psychosis Associated with Elevated Trough Tacrolimus Blood Concentrations 17 Years after Kidney Transplant." Case Reports in Psychiatry 2013 (2013): 1–3. http://dx.doi.org/10.1155/2013/926395.
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Several neurological side effects induced by tacrolimus are described in the scientific literature, ranging from mild neurological symptoms to delirium and psychosis. We report the case of a 46-year-old man with no prior psychiatric history who suddenly manifested manic-like psychosis associated with elevated trough tacrolimus blood concentrations 17 years after kidney transplant. The use of antipsychotics may improve the severity of symptoms; but in order to obtain a complete remission, the reduction in the dose of tacrolimus, or its replacement with alternative immunosuppressant therapies, is recommended.
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Barrantes-Vidal, Neus, Manel Monsonet, Anna Racioppi, and Thomas R. Kwapil. "M2. STRESS IS ASSOCIATED AND PREDICTS SCHIZOTYPIC AND PSYCHOTIC-LIKE EXPERIENCES IN THE FLOW OF DAILY LIFE IN NONCLINICAL AND INCIPIENT PSYCHOSIS INDIVIDUALS." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S133. http://dx.doi.org/10.1093/schbul/sbaa030.314.
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Abstract Background Daily-life stressors, specially of a social nature, seem to play an important role in the origin and expression of the continuum of psychosis vulnerability. This study examined whether social stress and social positive appraisals in daily-life were associated, respectively, with the occurrence and the decrease of momentary psychotic-like and paranoid experiences and symptoms across the psychosis continuum. Methods Both social stressors and positive appraisals, as well as psychotic and paranoid experiences, were collected by means of Experience Sampling Methodology over a week. Schizotypy was assessed with the Wisconsin Schizotypy Scales. Participants were 206 nonclinical individuals oversampled for schizotypy scores (mean age=19.8) and 113 individuals with at-risk mental states for psychosis and first episode psychosis (74 and 39, respectively; mean age=22.5). Results In the nonclinical sample, appraisals of social stress (but no social contact per se) were associated with psychotic-like and paranoid experiences in daily-life, but not with diminished thoughts or emotions (negative-like symptoms). The association of stress with psychotic and paranoid experiences was moderated by positive, but not negative, schizotypy. In the clinical sample, the positive social appraisal of feeling cared for by others moderated the association between negative self-esteem and the experience of paranoia. Also, they predicted (time-lagged analyses) a decrease of these experiences at subsequent time points—although only feeling cared about did so when the previous level of paranoia was controlled for. Discussion Consistent with models postulating that stress-sensitivity is a potential mechanistic pathway of, specifically, the positive dimension of psychosis, situational and also social stress predicted psychotic-like and paranoid experiences only in participants with high positive schizotypy. Furthermore, positive social appraisals showed a critical role for buffering the expression of paranoia associated to poor self-esteem in clinical risk for and early psychosis and predicted its amelioration prospectively. Altogether, these findings support the notion that increased sensitivity to social cues is a critical aspect for both risk and resilience mechanisms in the continuum of psychosis. Additionally, they highlight the powerful relevance of positive social identification for dampening the deleterious effects of poor self-esteem and stress.
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Tortelli, Andrea, Aurélie Nakamura, Federico Suprani, Franck Schürhoff, Judith Van der Waerden, Andrei Szöke, Ilaria Tarricone, and Baptiste Pignon. "Subclinical psychosis in adult migrants and ethnic minorities: systematic review and meta-analysis." BJPsych Open 4, no. 6 (November 2018): 510–18. http://dx.doi.org/10.1192/bjo.2018.68.
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BackgroundIt is well established that migration and ethnic minority status are risk factors for psychotic disorders. Recent studies have aimed to determine if they are also associated with subclinical psychosis (psychotic-like experiences and schizotypal traits).AimsWe aimed to determine to what extent migrant and ethnic minority groups are associated with higher risk of subclinical psychosis.MethodWe conducted a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and examined findings by ethnicity, migrant status, outcomes of subclinical psychosis and host country. A meta-analysis was carried out with robust variance estimation where possible, to handle statistically dependent effect size estimates.ResultsWe included 28 studies (19 studies on psychotic-like experiences and 9 studies on schizotypal traits) and found that ethnicity, but not migrant status, was associated with current and lifetime psychotic-like experiences. In the narrative analysis, we observed the effect of psychosocial risk factors on this association: Black ethnicity groups showed consistent increased prevalence of current and lifetime psychotic-like experiences compared with the reference population across countries.ConclusionsMore generalisable and standardised cohort studies of psychotic-like experiences and schizotypal traits in relation to migration/ethnicity are necessary to examine the effects of exposures and outcomes in different contexts, and to understand the underlying mechanisms of the association between subclinical psychosis and migrant and ethnic minority status.Declaration of interestNone.
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Carhart-Harris, R. L., M. Kaelen, M. Bolstridge, T. M. Williams, L. T. Williams, R. Underwood, A. Feilding, and D. J. Nutt. "The paradoxical psychological effects of lysergic acid diethylamide (LSD)." Psychological Medicine 46, no. 7 (February 5, 2016): 1379–90. http://dx.doi.org/10.1017/s0033291715002901.
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BackgroundLysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study.MethodA total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session.ResultsLSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking.ConclusionsThe present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of ‘loosened cognition’ in the mid to long term that is conducive to improved psychological wellbeing.
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Taylor, Hannah E., Sophie Parker, Warren Mansell, and Anthony P. Morrison. "Effects of Appraisals of Anomalous Experience on Distress in People at Risk of Psychosis." Behavioural and Cognitive Psychotherapy 41, no. 1 (May 1, 2012): 24–33. http://dx.doi.org/10.1017/s1352465812000227.
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Background: A cognitive model of psychosis suggests that appraisals of psychotic-like experiences (PLEs), and the subsequent responses adopted, are responsible for the maintenance of distress and disability associated with psychosis. Aims: This study aimed to investigate whether it is possible to manipulate appraisals of an anomalous experience in people at risk of psychosis and whether this affects levels of distress. Method: Participants who had experienced an “at risk mental state” (ARMS) within the past year, were randomized to one of two groups and received either negative or neutral information pertaining to an anomalous experience (a card trick). Participants completed a questionnaire measuring PLEs, then completed pre and post measures of distress and anxiety in relation to the card trick. Participants were also asked to rate a series of psychotic or non-psychotic appraisals regarding how they thought the card trick worked. Results: Data analysis revealed that distress and anxiety were not related to the information group assigned (our experimental manipulation was unsuccessful). However, when analyzed as one group, higher conviction in non-psychotic appraisals was found to be related to lower levels of distress and state anxiety. Conclusions: The findings provide some validation for a relationship between appraisals and distress. Clinical implications, methodological limitations and possible future research directions are discussed.
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Morgan, Celia J. A., and H. Valerie Curran. "Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis." British Journal of Psychiatry 192, no. 4 (April 2008): 306–7. http://dx.doi.org/10.1192/bjp.bp.107.046649.
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SummaryCannabis contains various cannabinoids, two of which have almost opposing actions: δ9-tetrahydrocannabinol (Δ9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of Δ9-THC and CBD in 140 individuals. Three clear groups emerged: ‘THC only’, ‘THC+CBD’ and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.
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Freeman, Abigail M., Claire Mokrysz, Chandni Hindocha, Will Lawn, Celia JA Morgan, Tom P. Freeman, Rob Saunders, and H. Valerie Curran. "Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis." Journal of Psychopharmacology 35, no. 7 (January 9, 2021): 804–13. http://dx.doi.org/10.1177/0269881120959601.
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Background: While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC). Methods: Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC. Results: There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo. Conclusions: Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.
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Mason, Oliver J. "Inducing Psychotic-like Experiences without Drugs using the Witches’ Cradle." Journal of Medical Psychology 1, no. 1 (November 6, 2020): 53–56. http://dx.doi.org/10.3233/jmp-190020.
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Various means of inducing unusual or anomalous experiences sharing similarities with psychosis have been proposed. In the present study, an ‘altered states of consciousness induction device’ (ASCID) or ‘witches’ cradle’ was used to suspend 81 participants for a short duration. The Psychotomimetic States Inventory recorded an increase in a wide variety of experiences following the cradle when compared to baseline. Psychotic-like experiences were predicted by greater positive schizotypal trait scores. Anomalous proprioceptive perceptual input appears to be capable for some individuals of inducing psychotic-like effects over a short time period.
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Ashinoff, Brandon, and Guillermo Horga. "Evidence-Order Effects in Probabilistic Inference: Recency Bias and Delusion-Like Ideation Across the Psychosis Continuum." Biological Psychiatry 87, no. 9 (May 2020): S392—S393. http://dx.doi.org/10.1016/j.biopsych.2020.02.1004.
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Cortes-Briones, Jose A., John D. Cahill, Patrick D. Skosnik, Daniel H. Mathalon, Ashley Williams, R. Andrew Sewell, Brian J. Roach, Judith M. Ford, Mohini Ranganathan, and Deepak Cyril D’Souza. "The Psychosis-like Effects of Δ9-Tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans." Biological Psychiatry 78, no. 11 (December 2015): 805–13. http://dx.doi.org/10.1016/j.biopsych.2015.03.023.
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Obayi, Okwudili N. K. "Acute schizophrenia-like psychotic disorder associated with immunosuppressive agent use three years after renal transplantation: a case report." International Journal of Scientific Reports 4, no. 7 (June 23, 2018): 192. http://dx.doi.org/10.18203/issn.2454-2156.intjscirep20182731.
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<p class="abstract">Tacrolimus is a potent immunosuppressive agent used to prevent graft-versus-host disease after organ transplantation. Though a beneficial drug that contributes in the post-transplant life of patients, it comes with various side effects including, though rarely, psychiatric manifestations such as psychosis.<strong> </strong>Reported here is the case of a 21 year old lady with no prior psychiatry history with apparent tacrolimus-induced schizophrenia-like psychosis. Withdrawal of the immunosuppressant led her to full recovery from the mental problem. To the best of my knowledge, there are only few reports that describe psychosis induced by tacrolimus but none of such reports is from Nigeria, a country with increasing demand for kidney transplant. Clinicians are reminded to regularly watch out for mental status changes in post-transplant patients as early identification of any aberration with immediate reduction of the dosage or substitution of the drug would save both the patient and the already emotionally and financially-stressed family from further distress.</p>
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van der Feltz-Cornelis, Cm. "Treatment of interictal psychiatric disorder in epilepsy. II. Chronic psychosis." Acta Neuropsychiatrica 14, no. 1 (February 2002): 44–48. http://dx.doi.org/10.1034/j.1601-5215.2002.140107.x.
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Background:Interictal psychosis is a serious comorbid condition in epilepsy patients that would benefit from treatment with psychotropic medication.Objective:This paper gives an overview of the pathophysiology, symptomatology and treatment of the schizophrenia-like psychosis of epilepsy. Use of the term ‘interictal chronic psychosis’ is suggested, to conform to current DSM-IV classification of schizophrenia.Methods:Literature review supplemented by clinical experience. There is a lack of randomized control trials (RCTs) concerning effectiveness and side-effects of neuroleptics in epilepsy patients.Results:Hypotheses concerning the pathophysiology of the interictal chronic psychosis are discussed. The concept of forced normalization and alternative psychosis is based on case descriptions, and was not substantiated by systematic research. The kindling hypothesis seems promising, but was never confirmed in humans. A third theory, supported by some studies, suggests that inhibitory cerebral mechanisms enhance psychotic symptoms in epilepsy patients. Treatment strategies are based on case studies and open studies by lack of RCTs. Treatment should consider the optimalization of the dosage of antiepileptics in combination with one or two antidepressants, mood stabilizers and/or atypical neuroleptics. Surgery plays no significant role in the treatment of treatment-refractive epilepsy with interictal chronic psychotic symptoms.Conclusion:There is a prominent role of antidepressant or double antidepressant treatment strategies in patients with epilepsy and interictal chronic psychosis compared with treatment guidelines of chronic psychotic patients in general psychiatry.
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Grant, Phillip, Aisha Judith Leila Munk, Yvonne Kuepper, Catrin Wielpuetz, and Juergen Hennig. "Additive Genetic Effects for Schizotypy Support a Fully-Dimensional Model of Psychosis-Proneness." Journal of Individual Differences 36, no. 2 (April 10, 2015): 87–92. http://dx.doi.org/10.1027/1614-0001/a000155.
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Schizotypy is an organization of traits mirroring psychosis-like symptoms and conveying individual psychosis-proneness. Schizotypy and schizophrenia share a genetic basis, wherefore initial schizotypy definitions considered a schizophrenic genotype as a condicio sine qua non. Since the search for a monogenetic schizotypy marker has proven in vain, it is believed that schizotypy is (genetically) based on multiple alleles, each of small effect-size. Schizophrenia may be viewed as a qualitative entity at the extreme of the schizotypy dimension. To date, however, it has not been shown that effects of individual schizotypy-related alleles or genotypes are additive, which would be necessary for the proposition of latent genetic schizotypy factors. Based on previous findings of significant associations of candidate polymorphisms with schizotypy, we chose to examine if these genetic effects were, indeed, additive regarding positive schizotypy. Using a sample of 288 healthy participants we calculated allele-wise and genotype-wise risk indices and examined, whether levels of positive schizotypy would significantly increase with genetic risk. Our findings show significant additive genetic effects of select polymorphisms on positive schizotypy and, thus, support the notion of a fully-dimensional and partially genetically based model of schizotypy.
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Ebert, Dieter, Roland Albert, Albrecht May, Antje Merz, Harumi Murata, Isolde Stosiek, and Birgit Zahner. "The serotonin syndrome and psychosis-like side-effects of fluvoxamine in clinical use – an estimation of incidence." European Neuropsychopharmacology 7, no. 1 (February 1997): 71–74. http://dx.doi.org/10.1016/s0924-977x(96)00043-0.
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Reeves, S., R. Stewart, and R. Howard. "Service contact and psychopathology in very-late-onset schizophrenia-like psychosis: the effects of gender and ethnicity." International Journal of Geriatric Psychiatry 17, no. 5 (2002): 473–79. http://dx.doi.org/10.1002/gps.614.
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Scott, Daniel, and Carol A. Tamminga. "Effects of genetic and environmental risk for schizophrenia on hippocampal activity and psychosis-like behavior in mice." Behavioural Brain Research 339 (February 2018): 114–23. http://dx.doi.org/10.1016/j.bbr.2017.10.039.
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Ganesh, Suhas, Jose Cortes-Briones, Mohini Ranganathan, Rajiv Radhakrishnan, Patrick D. Skosnik, and Deepak Cyril D’Souza. "Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies." International Journal of Neuropsychopharmacology 23, no. 9 (May 9, 2020): 559–70. http://dx.doi.org/10.1093/ijnp/pyaa031.
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Abstract Introduction There is increasing interest in the relationship between cannabinoids and psychosis. While individual human laboratory studies have been critical in demonstrating that cannabinoids (e.g., delta-9-tetrahydrocannabinol [THC]) can induce acute transient psychosis-like effects in healthy human volunteers, combining data from multiple studies offers a fine-grained view of these effects. Methods THC-induced psychosis-relevant effects were examined using a data repository of 10 double-blind, randomized, placebo-controlled, crossover studies with 400 i.v. THC infusions in healthy human volunteers. The Positive and Negative Syndrome scale was used to measure psychotomimetic effects. The profile of symptoms, frequency of a response, its relationship to THC dose and substance use, latent structure in Positive and Negative Syndrome scale response, and the relationships between psychotomimetic and perceptual alteration symptoms were evaluated. Results Clinically meaningful increases in positive symptoms were noted in 44.75% infusions; conceptual disorganization, hallucinations, blunted affect, somatic concern, motor retardation, and poor attention were the items most frequently altered by THC. The increase in Positive and Negative Syndrome scale positive symptoms was positively associated with THC dose (beta = 11.13, SE = 4.94, Wald χ 2 = 19.88, P < .001) and negatively associated with frequent cannabis use (beta = −0.575, SE = 0.14, Wald χ 2 = 18.13, P < .001). Furthermore, positive symptoms were strongly correlated with Clinician Administered Dissociative States Scale perceptual alterations score (rs = 0.514, P < .001). Conclusion Intravenous administration of THC consistently induces psychotomimetic effects that include symptoms across Positive and Negative Syndrome scale domains. Moreover, healthy individuals who frequently use cannabis have a blunted psychotomimetic response.
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Morgan, C. J. A., C. Gardener, G. Schafer, S. Swan, C. Demarchi, T. P. Freeman, P. Warrington, et al. "Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being." Psychological Medicine 42, no. 2 (July 29, 2011): 391–400. http://dx.doi.org/10.1017/s0033291711001322.
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BackgroundCannabis varies considerably in levels of its two major constituent cannabinoids – (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being.MethodA total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety.ResultsLower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.ConclusionsCBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as ‘skunk’ (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.
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Tsopelas, C., M. Dimitraka, P. Ntounas, A. Gatos-Gatopoulos, D. Karadima, and T. Charalampos. "Use of cannabis components in the treatment of mental disorders." European Psychiatry 33, S1 (March 2016): S552. http://dx.doi.org/10.1016/j.eurpsy.2016.01.2036.
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IntroductionThere is evidence that supports the increased risk of developing psychosis or psychotic like symptoms in vulnerable populations after use of cannabis. Cannabis’ main psychoactive component, Δ9-tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. But there is also evidence to suggest that molecules in the cannabis plant could have an antipsychotic affect.AimsIn this review we are trying to explore the possibilities of cannabis use as a therapeutic agent in mental disorders.MethodsThorough research of the main databases, and web search engines for relevant studies, using appropriate keywords. We scrutinize them independently, before reaching consensus about appropriateness.ResultsIn animal models repeated treatment with cannabis constituent cannabidiol CBD or the atypical antipsychotic clozapine attenuates or reverses the schizophrenia-like behavioral disruption.In humans there are data that CBD counteracts psychotic symptoms and cognitive impairment associated with cannabis use. Also CBD may lower the risk for developing cannabis use associated psychosis. There are opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex.ConclusionsThe possible mechanism of action of GBD is not fully clarified, as it may involve anti-inflammatory or neuroprotective properties. These initial clinical studies with CBD treatment of psychotic symptoms argument the potential of CBD as an effective antipsychotic compound. Mechanisms responsible for these effects need to be further investigated.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Kilciksiz, Can, and John Torous. "T105. VERBAL MEMORY MEASUREMENT TOWARDS DIGITAL PERSPECTIVES IN FIRST-EPISODE PSYCHOSIS: A SYSTEMATIC REVIEW STUDY." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S270—S271. http://dx.doi.org/10.1093/schbul/sbaa029.665.
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Abstract Background Psychosis is a clinical syndrome which can have detrimental effects on patients in different aspects of functioning such as thought, behavior, and cognition. Even in early phases psychotic spectrum illnesses like schizophrenia, patients can experience cognitive decline prior to overt classical symptoms like delusions and hallucinations. Early detection and reducing the duration of untreated psychosis through early intervention can prevent or slow the progress of cognitive symptoms and the entire illness. Although cognition research in early psychosis has demonstrated that verbal memory is one the first cognitive domains impacted in first-episode of psychosis and continuously declines after the first-episode, it is still not clear which tests are most widely used to measure verbal memory and which may be most amenable to being translated to a digital format. In this systematic review, we assessed which verbal memory assessments are most widely used in first-episode psychosis and may be potentially applied via digital technologies (smartphone applications, telepsychiatry, chatbots, etc.) for use in early detection in the future. Methods From September to November 2019, we searched studies measured verbal memory in first-episode psychosis or schizophrenia over the past 10 years on PubMed and PsycINFO. We screened abstracts of these studies and we excluded review studies and duplicates. We downloaded full-texts of included studies to identify the verbal memory measurement tests used, follow-up frequencies, and sample sizes. Results We screened 233 papers and found that 121 original research studies measured verbal memory in first-episode psychosis over the past 10 years. Of these 121 studies, 32(%26) used Rey Auditory Verbal Learning Test (RAVLT), 29(24%) used California Verbal Learning Test (CVLT), 27(22%) used Weschler Memory Scale (WMS), 14(12%) used Hopkins Verbal Learning Test (HVLT), 4(3%) used both WMS and CVLT, 3(2%) used both WMS and RAVLT, and 12(%10) used other tests to measure verbal memory. Four (3%) of these studies specified that they used a computer, 23(20%) used paper-pen, 2(2%) studies used both, and 92(76%) studies did not specify their verbal measurement application tools. Thirty-six (30%) studies had follow-up measurements of verbal memory, while 85(70%) studies had only a single time point verbal memory measurement during the study period. Study sample sizes range from 6 to 498. Discussion We found that four main tests to measure verbal memory in first-episode psychosis are RAVLT, CVLT, WMS, and HVLT although they are not often administered via technology. Of these four verbal memory measurement tests, RAVLT is the most widely used and HVLT is easier to administer while CVLT appears able to assess a broader range of verbal memory domains. There is an emerging opportunity to apply RAVLT, CVLT, WMS, and HVLT via digital technologies for expanding access to early detection of cognitive decline in clinical high risk and first-episode psychosis.
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Radhika Tyagi, Sangrila Singh, Anjali Joshi, Vishali Chopra, Priyank Vyas, and Amit Gupta. "Overview of Salvia divinorum –Substance-induced psychosis." International Journal of Research in Pharmaceutical Sciences 11, SPL4 (December 21, 2020): 1714–18. http://dx.doi.org/10.26452/ijrps.v11ispl4.4360.
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As per the literature, humans ingest a comprehensive range of food materials including drugs along with dietary supplements which are mainly derived through medicinal plant products and modifying the purpose of the central nervous system (CNS). These psychoactive based properties are mainly attributable to the existence of plant-derived secondary metabolites. Most of the cases or studies showed the effects of these phytochemicals derived from secondary metabolites on the human CNS might be linked either to their ecological roles or molecular along with biochemical based properties are reported in case of plants along with higher animals. One of the mental health disorders, psychosis where person losses its capacity of critical thinking, they perceive things differently as compared to the people around. They see or hear things that other people cannot see or hear (hallucination) or even believe things that are not true (delusion). There are so many synthetic psychosis inducer synthetic cannabinoids (SCs) as well as semi-synthetic and natural. Psychosis is a disorder which shows the effect for long-term or sometimes for the short term on an individual. In this review we will mainly look for natural psychosis inducers like Salvia divinorum and this plant may produce some secondary metabolites. Still, many of these are found to show an effect on human health in some or the other way which may range from hallucination to organ failure. These secondary metabolites affect the hippocampus region of the human brain, which is linked with memory. It is interesting to note how one chemical is used for an organism for protection and that one chemical act as a mind-altering chemical for the higher class of organism – the humans.
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Howard, Robert, Elizabeth Cort, Rosie Bradley, Emma Harper, Linda Kelly, Peter Bentham, Craig Ritchie, et al. "Amisulpride for very late-onset schizophrenia-like psychosis: the ATLAS three-arm RCT." Health Technology Assessment 22, no. 67 (November 2018): 1–62. http://dx.doi.org/10.3310/hta22670.
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Background Very late-onset (aged ≥ 60 years) schizophrenia-like psychosis (VLOSLP) occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy or risks of antipsychotic treatment. Most patients are not prescribed treatment. Objectives The study investigated whether or not low-dose amisulpride is superior to placebo in reducing psychosis symptoms over 12 weeks and if any benefit is maintained by continuing treatment thereafter. Treatment safety and cost-effectiveness were also investigated. Design Three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial. Participants who received at least one dose of study treatment were included in the intention-to-treat analyses. Setting Secondary care specialist old age psychiatry services in 25 NHS mental health trusts in England and Scotland. Participants Patients meeting diagnostic criteria for VLOSLP and scoring > 30 points on the Brief Psychiatric Rating Scale (BPRS). Intervention Participants were randomly assigned to three arms in a two-stage trial: (1) 100 mg of amisulpride in both stages, (2) amisulpride then placebo and (3) placebo then amisulpride. Treatment duration was 12 weeks in stage 1 and 24 weeks (later reduced to 12) in stage 2. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures Primary outcomes were psychosis symptoms assessed by the BPRS and trial treatment discontinuation for non-efficacy. Secondary outcomes were extrapyramidal symptoms measured with the Simpson–Angus Scale, quality of life measured with the World Health Organization’s quality-of-life scale, and cost-effectiveness measured with NHS, social care and carer work loss costs and EuroQol-5 Dimensions. Results A total of 101 participants were randomised. Ninety-two (91%) participants took the trial medication, 59 (64%) completed stage 1 and 33 (56%) completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7.7 points (95% CI 3.8 to 11.5 points) greater with amisulpride than with placebo (11.9 vs. 4.2 points; p = 0.0002). In stage 2, BPRS scores improved by 1.1 point in those who continued with amisulpride but deteriorated by 5.2 points in those who switched from amisulpride to placebo, a difference of 6.3 points (95% CI 0.9 to 11.7 points; p = 0.024). Fewer participants allocated to the amisulpride group stopped treatment because of non-efficacy in stages 1 (p = 0.01) and 2 (p = 0.031). The number of patients stopping because of extrapyramidal symptoms and other side effects did not differ significantly between groups. Amisulpride treatment in the base-case analyses was associated with non-significant reductions in combined NHS, social care and unpaid carer costs and non-significant reductions in quality-adjusted life-years (QALYs) in both stages. Including patients who were intensive users of inpatient services in sensitivity analyses did not change the QALY result but resulted in placebo dominance in stage 1 and significant reductions in NHS/social care (95% CI –£8923 to –£122) and societal costs (95% CI –£8985 to –£153) for those continuing with amisulpride. Limitations The original recruitment target of 300 participants was not achieved and compliance with trial medication was highly variable. Conclusions Low-dose amisulpride is effective and well tolerated as a treatment for VLOSLP, with benefits maintained by prolonging treatment. Potential adverse events include clinically significant extrapyramidal symptoms and falls. Future work Trials should examine the longer-term effectiveness and safety of antipsychotic treatment in this patient group, and assess interventions to improve their appreciation of potential benefits of antipsychotic treatment and compliance with prescribed medication. Trial registration Current Controlled Trials ISRCTN45593573 and EudraCT2010-022184-35. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 67. See the NIHR Journals Library website for further project information.
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Stramecki, Filip, Dorota Frydecka, Łukasz Gawęda, Katarzyna Prochwicz, Joanna Kłosowska, Jerzy Samochowiec, Krzysztof Szczygieł, et al. "The Impact of the FKBP5 Gene Polymorphisms on the Relationship between Traumatic Life Events and Psychotic-Like Experiences in Non-Clinical Adults." Brain Sciences 11, no. 5 (April 28, 2021): 561. http://dx.doi.org/10.3390/brainsci11050561.
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Common variations of the FKBP5 gene are implicated in psychotic disorders, by modulating the hypothalamic–pituitary–adrenal axis reactivity to stress. It has been demonstrated that some of them might moderate the effects of childhood trauma on psychosis proneness. However, these associations have not been investigated with respect to traumatic life events (TLEs). Therefore, we aimed to explore whether the FKBP5 polymorphisms moderate the effects of TLEs on the level of psychotic-like experiences (PLEs). A total of 535 non-clinical adults were approached for participation, and genotyping of six FKBP5 polymorphisms (rs3800373, rs9470080, rs4713902, rs737054, rs1360780 and rs9296158) was performed. The Prodromal Questionnaire-16 (PQ-16) and the Traumatic Events Checklist (TEC) were administered to assess PLEs and TLEs, respectively. Among the rs1360780 CC homozygotes, a history of physical abuse was associated with significantly higher PQ-16 scores. This difference was not significant in the rs1360780 T allele carriers. Similarly, a history of physical abuse was associated with significantly higher PQ-16 scores in the rs9296158 GG homozygotes but not in the rs9296158 A allele carriers. Finally, emotional neglect was related to significantly higher PQ-16 scores in the rs737054 T allele carriers but not in the rs737054 CC homozygotes. The present study indicates that variation in the FKBP5 gene might moderate the effects of lifetime traumatic events on psychosis proneness.
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Irankunda, Pacifique, and Laurie Heatherington. "Mental health treatment outcome expectancies in Burundi." Transcultural Psychiatry 54, no. 1 (July 9, 2016): 46–65. http://dx.doi.org/10.1177/1363461516652302.
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Best practices in global mental health stress the importance of understanding local values and beliefs. Research demonstrates that expectancies about the effectiveness of a given treatment significantly predicts outcome, beyond the treatment effect itself. To help inform the development of mental health interventions in Burundi, we studied expectancies about the effectiveness of four treatments: spiritual healing, traditional healing, medication, and selected evidence-based psychosocial treatments widely used in the US. Treatment expectancies were assessed for each of three key syndromes identified by previous research: akabonge (a set of depression-like symptoms), guhahamuka (a set of trauma-related symptoms), and ibisigo (a set of psychosis-like symptoms) . In individual interviews or written surveys in French or Kirundi with patients ( N = 198) awaiting treatment at the clinic, we described each disorder and the treatments in everyday language, asking standard efficacy expectations questions about each (“Would it work?” “Why or why not?”). Findings indicated uniformly high expectancies about the efficacy of spiritual treatment, relatively high expectancies for western evidence-based treatments (especially cognitive behavior therapy [CBT] for depression-like symptoms), lower expectancies for medicine, and especially low expectancies for traditional healing (except for traditional healing for psychosis-like symptoms). There were significant effects of gender but not of education level. Qualitative analyses of explanations provide insight into the basis of people’s beliefs, their explanations about why a given treatment would or would not work varied by type of disorder, and reflected beliefs about underlying causes. Implications for program development and future research are discussed.
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Ciufolini, Simone, Matthew Kempton, Charlotte Gayer-Anderson, Heather Taylor, Tiago Reis Marques, Helen Fisher, Marta Di Forti, et al. "S186. THE EFFECTS OF CHILDHOOD TRAUMA ON HIPPOCAMPAL VOLUME IN FIRST EPISODE PSYCHOSIS: DOES CORTISOL PLAY A ROLE?" Schizophrenia Bulletin 46, Supplement_1 (April 2020): S109. http://dx.doi.org/10.1093/schbul/sbaa031.252.
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Abstract Background Childhood trauma is one of the most important risk factors in psychosis. Mounting evidence is associating early trauma exposure with alterations in stress sensitive areas, like the hippocampus, and abnormal concentrations of the main stress hormone, cortisol. As hippocampus is a pivotal brain region in the hypothalamus–pituitary–adrenal (HPA) axis regulation of cortisol, better understanding the relationship between childhood trauma, hippocampus structure and cortisol concentration would help clarify how childhood trauma exposure can increase the risk of developing psychosis later on in life. Methods Brain structure was evaluated with a 3T MRI scan in 86 first episode psychosis patients (FEP) (49 of which positive for severe childhood trauma) (mean age: 27.8 SD ± 9.1 years). Hippocampal volume and the segmentation of the hippocampal subfields was obtained using FreeSurfer 6. Salivary cortisol samples were collected to measure cortisol levels at awakening (CAR). Initially two separate linear regression models were ran: 1) to predict hippocampal volume changes with childhood trauma as the independent variable and 2) to predict hippocampal volume changes with CAR as independent variable. Finally, we introduced CAR as moderator in the linear model 1 to explore whether it changed the relationship between childhood abuse and hippocampal volume. Results Individuals with psychosis and severe childhood abuse presented smaller volume of the right hippocampal head (β = -108.9, p = 0.027), particularly in subfields CA1, CA3, CA4 and in the right GC-ML-DG head (all significant at p < 0.05 with βs between – 110 and -90) (linear model 1). CAR did not predict changes in hippocampal volumes (linear model 2). However, when CAR was introduced the relationship between childhood abuse and hippocampal volume (linear model 1) it showed a moderator role. Indeed low levels of CAR were associated with an even further reduction in hippocampal volume in the right hippocampal head and particularly in subfields CA1, CA3 and CA4 (all significant at p < 0.05 and βs between – 150 and -180). Discussion These results suggest that exposure to childhood trauma has a long-term effect on the adult brain particularly in hippocampal areas related to the encoding and retrieval of memories. Importantly, low levels of CAR are associated with even smaller hippocampal head in patients who childhood trauma This is particularly important, because an abnormal hippocampal structure could alter the hippocampal feedback on the HPA axis leading to dysfunctional (lower) cortisol production, which in turn would amplify the impact on brain stress sensitive regions of further stress exposure.
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Kostic, Velimir, Maja Jovanovic, Jelena Radovic, and Stevan Vujic. "Side effects of antiviral therapy in patients with chronic hepatitis C infection." Medical review 65, no. 3-4 (2012): 106–10. http://dx.doi.org/10.2298/mpns1204106k.
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Introduction. Chronic hepatitis C currently represents a global health problem, which is expected to be reduced by pegylated-interferon and ribavirin therapy. Material and Methods. We examined 88 patients with chronic hepatitis C, divided into three groups according to their comorbidity: the patients without comorbidity were in group I, group II included the patients on dialysis, and group III included the patients with hemophilia. Results. A significant difference was found in the percentage of achieved sustained virological response between the patients on dialysis and other patients, p<0.05. Having analyzed the therapy adverse effects, we observed a significantly higher decrease of erythrocytes count, hemoglobin and hematocrit levels in dialysis patients compared to others (p<0.01). The patients on hemodialysis predominantly had anemia and leukopenia, while thrombocytopenia was equally present in all groups. The dominant clinical side effect was flu-like syndrome, present in more than a half of patients. Discussion. The therapy positive effect is usually accompanied with adverse effects. The lowest therapeutic response was recorded in group II, due to the virus genotype 1. A significant decrease in hematological parameters was determined in all patients. The most common clinical adverse effect was flu-like syndrome, later manifestations included: weight loss, alopecia, insomnia and irritability. Side effects like psychosis, thyroid gland dysfunction or psoriasis were not recorded. Conclusion. A significant decrease in the value of all these hematological parameters was found in all groups of patients. Clinical side effects were present in 60% of patients. Side effects did not lead to discontinuation of therapy, but only to modification of drug doses.
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Colizzi, Marco, Nathalie Weltens, Philip McGuire, David Lythgoe, Steve Williams, Lukas Van Oudenhove, and Sagnik Bhattacharyya. "Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis." Molecular Psychiatry 25, no. 12 (February 15, 2019): 3231–40. http://dx.doi.org/10.1038/s41380-019-0374-8.
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AbstractThe neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.
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Ermakova, Anna O., Nimrod Gileadi, Franziska Knolle, Azucena Justicia, Rachel Anderson, Paul C. Fletcher, Michael Moutoussis, and Graham K. Murray. "Cost Evaluation During Decision-Making in Patients at Early Stages of Psychosis." Computational Psychiatry 3 (August 2019): 18–39. http://dx.doi.org/10.1162/cpsy_a_00020.
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Jumping to conclusions during probabilistic reasoning is a cognitive bias reliably observed in psychosis and linked to delusion formation. Although the reasons for this cognitive bias are unknown, one suggestion is that psychosis patients may view sampling information as more costly. However, previous computational modeling has provided evidence that patients with chronic schizophrenia jump to conclusions because of noisy decision-making. We developed a novel version of the classical beads task, systematically manipulating the cost of information gathering in four blocks. For 31 individuals with early symptoms of psychosis and 31 healthy volunteers, we examined the numbers of “draws to decision” when information sampling had no, a fixed, or an escalating cost. Computational modeling involved estimating a cost of information sampling parameter and a cognitive noise parameter. Overall, patients sampled less information than controls. However, group differences in numbers of draws became less prominent at higher cost trials, where less information was sampled. The attenuation of group difference was not due to floor effects, as in the most costly block, participants sampled more information than an ideal Bayesian agent. Computational modeling showed that, in the condition with no objective cost to information sampling, patients attributed higher costs to information sampling than controls did, Mann–Whitney U = 289, p = 0.007, with marginal evidence of differences in noise parameter estimates, t(60) = 1.86, p = 0.07. In patients, individual differences in severity of psychotic symptoms were statistically significantly associated with higher cost of information sampling, ρ = 0.6, p = 0.001, but not with more cognitive noise, ρ = 0.27, p = 0.14; in controls, cognitive noise predicted aspects of schizotypy (preoccupation and distress associated with delusion-like ideation on the Peters Delusion Inventory). Using a psychological manipulation and computational modeling, we provide evidence that early-psychosis patients jump to conclusions because of attributing higher costs to sampling information, not because of being primarily noisy decision makers.
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Correia, Banny Silva Barbosa, João Victor Nani, Raniery Waladares Ricardo, Danijela Stanisic, Tássia Brena Barroso Carneiro Costa, Mirian A. F. Hayashi, and Ljubica Tasic. "Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia." Biomedicines 9, no. 3 (February 26, 2021): 235. http://dx.doi.org/10.3390/biomedicines9030235.
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Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.
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Antoniades, Mathilde, Igor Nenadic, Tilo Kircher, Alex Krug, Tina Meller, Dominik Grotegerd, Alex Fornito, et al. "M156. CORTICAL NEUROANATOMICAL SIGNATURE OF SCHIZOTYPY IN 2,695 INDIVIDUALS ASSESSED IN A WORLDWIDE ENIGMA STUDY." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S195. http://dx.doi.org/10.1093/schbul/sbaa030.468.
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Abstract Background Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to control for multiple comparisons. Results We found significant positive associations between subclinical psychotic-like experiences and mean cortical thickness of the medial orbitofrontal cortex (r = .077; pFDR = .006) and the frontal pole (r = .073; pFDR = .006). When assessed separately by hemisphere, meta-analysis revealed a significant positive association between subclinical psychotic-like experiences and cortical thickness of the left medial orbitofrontal cortex (r = .066; pFDR = .044), and at trend-level with the right medial orbitofrontal cortex (r = .062; pFDR = .053) and the left frontal pole (r = .062; pFDR = .053). No significant associations were observed for surface area. Discussion Worldwide cooperative analyses of large-scale brain imaging data support a profile of cortical thickness abnormalities involving prefrontal cortical regions positively related to schizotypy in healthy individuals. These findings are not secondary to potential influences of disease chronicity or antipsychotic medication on the neuroanatomical correlates of psychotic-like experiences. The directionality of the observed meta-analytical effects in schizotypy is opposite to those previously reported in patients with schizophrenia (i.e., thinner cortex). The present findings of increased thickness may indicate early microstructural deficits (e.g. in myelination) that contribute to vulnerability for psychosis. Alternatively, these may reflect mechanisms of resilience associated with the expression of subclinical manifestations of psychotic symptoms in otherwise healthy individuals.
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Inta, D., J. Lima, D. Filipovic, G. Köhr, R. Sprengel, and P. Gass. "C-Fos brain mapping of global and subunit-specific NMDA receptor antagonists: Relevance for their potential use as antidepressants." European Psychiatry 26, S2 (March 2011): 639. http://dx.doi.org/10.1016/s0924-9338(11)72345-8.
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IntroductionNMDA receptor antagonists as ketamine represent fast-acting alternatives to monoaminergic-based antidepressants. Major drawbacks of these drugs are psychosis-like states and cortical neurotoxicity, effects correlating with potent activation of the cingulated and retrosplenial cortex. The molecular mechanisms underlying these side-effects have not been deciphered yet.AimsWe aimed to determine potential molecular components of the NMDA receptor implicated in their psychotomimetic action and investigated whether subunit-specific NMDA receptor antagonists also induce similar neurotoxic changes as ketamine.MethodTo investigate deleterious effects of NMDA receptor antagonists, we used brain mapping with the immediate early gene c-Fos. We analyzed the expression pattern of c-Fos in brain areas responsible for deleterious adverse events, after treatment with ketamine and the NR2B subunit-specific antagonist Ro 25-6981, both in wild-type and knockout mice, lacking either the entire NR2A subunit (NR2A ko mice) or its intracellular C-terminus (NR2A deltaC mice).ResultsIn contrast to ketamine (10mg/kg), Ro 25-6981, even at high dosages (50mg/kg) does not induce any c-Fos expression in the cingulated and retrosplenial cortex of wildtype mice. However, Ro 65-2981 evokes, both in NR2A ko mice and NR2A deltaC mice, strong c-Fos expression in these areas.ConclusionsOur data indicate that blockade of both NR2A and NR2B subunits is necessary to induce deleterious effects specific for ketamine. Deletion of the C-terminus of the NR2A subunit is sufficient to disinhibit, together with pharmacological NR2B blockade, neuronal networks associated with psychosis. Therefore, NR2B antagonists may represent safer alternatives to ketamine as potential antidepressants.
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Ruhrmann, S. "Intervention in Clinical High Risk States - Current Status and Future Perspectives." European Psychiatry 41, S1 (April 2017): S27—S28. http://dx.doi.org/10.1016/j.eurpsy.2017.01.140.
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IntroductionDuring the last twenty years, international efforts advanced the prevention of psychosis considerably. However, improved predictions as well as well-tolerated and needs-tailored interventions are still required.ObjectivesPrediction and Prevention of PsychosisAims Presenting the current state and new developments, including the European Union funded multi-center project PRONIA with regard to prediction (www.pronia.eu, 7th Framework Programme grant agreement n° 602152) and the German multi-center trial ESPRIT funded by the Federal Ministry of Education and Research (BMBF grants 01EE1407 C and 01EE1407I) with regard to prevention.MethodsResults of meta-analyses will be presented and discussed with regard to achievements and challenges. Possible advances by current projects will be discussed.ResultsPharmacological as well as psychological prevention has been shown to reduce the incidence rate of psychosis in the respective samples considerably. However, particularly social and role functioning, which are prognostically most important, are still an unsolved challenge. Furthermore, new interventions providing an improved tolerability and acceptance by the patients are required. On the level of prediction, a further improvement of predictive validity, particularly with regard to individualized risk estimation is desired.ConclusionsThe achievements in the field of prevention of psychosis are impressive, but further progress is needed. This should be achieved by studies like PRONIA, which aims at improving risk estimation by an advanced assessment concept as well as a sophisticated data analysis, and ESPRIT, which compares the effects of N-Acetylcysteine with an innovative, modular psychological prevention program focusing not only stress and symptom management, but also social cognitive domains.Disclosure of interestConsultant to Boehringer Ingelheim lecture fees by Boehringer Ingelheim, Otsuka travel grant by Servier.
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Smigielski, Lukasz, Diana Wotruba, Valerie Treyer, Julian Rössler, Sergi Papiol, Peter Falkai, Edna Grünblatt, Susanne Walitza, and Wulf Rössler. "The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study." Schizophrenia Bulletin 47, no. 5 (April 20, 2021): 1495–508. http://dx.doi.org/10.1093/schbul/sbab034.
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Abstract Background Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics. Method This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined. Results An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis–stress models. Conclusions Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.
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Daniel, Christina, and Oliver J. Mason. "Predicting Psychotic-Like Experiences during Sensory Deprivation." BioMed Research International 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/439379.
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Aims. This study aimed to establish the contribution of hallucination proneness, anxiety, suggestibility, and fantasy proneness to psychotic-like experiences (PLEs) reported during brief sensory deprivation.Method. Twenty-four high and 22 low hallucination-prone participants reported on PLEs occurring during brief sensory deprivation and at baseline. State/trait anxiety, suggestibility, and fantasy proneness were also measured.Results. Both groups experienced a significant increase in PLEs in sensory deprivation. The high hallucination prone group reported more PLEs both at baseline and in sensory deprivation. They also scored significantly higher on measures of state/trait anxiety, suggestibility, and fantasy proneness, though these did not explain the effects of group or condition. Regression analysis found hallucination proneness to be the best predictor of the increase in PLEs, with state anxiety also being a significant predictor. Fantasy proneness and suggestibility were not significant predictors.Conclusion. This study suggests the increase in PLEs reported during sensory deprivation reflects a genuine aberration in perceptual experience, as opposed to increased tendency to make false reports due to suggestibility of fantasy proneness. The study provides further support for the use of sensory deprivation as a safe and effective nonpharmacological model of psychosis.
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Thomas, Robert J., and David R. Reagan. "Association of a Tourette-Like Syndrome with Ofloxacin." Annals of Pharmacotherapy 30, no. 2 (February 1996): 138–41. http://dx.doi.org/10.1177/106002809603000205.
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OBJECTIVE: To describe the association between the use of the fluoroquinolone ofloxacin in an elderly man and an unusual acute encephalopathy with characteristics suggestive of Tourette's syndrome. CASE SUMMARY: An unusual syndrome was observed in a 71-year-old man temporally related to the initiation of ofloxacin therapy that resolved completely after discontinuation of the drug. The most remarkable phenomena were spitting and profuse swearing; other features were echolalia, echopraxia, orofacial and limb automatisms, hypersalivation, and amnesia for the episode on recovery. The clinical syndrome had several features in common with Tourette's syndrome and possibly with frontal lobe onset complex partial seizures. The electroencephalographic, neuroradiologic, and cerebrospinal fluid examinations were normal. DISCUSSION: The reported neurotoxic effects of the fluoroquinolones include insomnia, seizures, delirium, and psychosis, best explained by the gamma-aminobutyric acid—antagonistic properties of this class of drugs. This is the first reported case of a Tourette-like syndrome associated with the use of any quinolone, suggesting a possible interaction with central dopaminergic neurotransmitter systems. CONCLUSIONS: Use of drugs such as ofloxacin that have improved central nervous system penetration, disease- or age-related reductions in renal function, concomitant use of drugs such as theophylline and nonsteroidal antiinflammatory drugs, and possibly increased pharmacodynamic sensitivity place the elderly at special risk for quinolone neurotoxicity. Dosing modifications and an awareness of possible central nervous system adverse effects are warranted.
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de Castro-Catala, Marta, Neus Barrantes-Vidal, Tamara Sheinbaum, Artal Moreno-Fortuny, Thomas R. Kwapil, and Araceli Rosa. "COMT-by-Sex Interaction Effect on Psychosis Proneness." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/829237.
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Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
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Uzuneser, Taygun C., Eva-Maria Weiss, Jana Dahlmanns, Liubov S. Kalinichenko, Davide Amato, Johannes Kornhuber, Christian Alzheimer, et al. "Presynaptic vesicular accumulation is required for antipsychotic efficacy in psychotic-like rats." Journal of Psychopharmacology 35, no. 1 (December 4, 2020): 65–77. http://dx.doi.org/10.1177/0269881120965908.
Full textAbstract:
Background: The therapeutic effects of antipsychotic drugs (APDs) are mainly attributed to their postsynaptic inhibitory functions on the dopamine D2 receptor, which, however, cannot explain the delayed onset of full therapeutic efficacy. It was previously shown that APDs accumulate in presynaptic vesicles during chronic treatment and are released like neurotransmitters in an activity-dependent manner triggering an auto-inhibitory feedback mechanism. Although closely mirroring therapeutic action onset, the functional consequence of the APD accumulation process remained unclear. Aims: Here we tested whether the accumulation of the APD haloperidol (HAL) is required for full therapeutic action in psychotic-like rats. Methods: We designed a HAL analog compound (HAL-F), which lacks the accumulation property of HAL, but retains its postsynaptic inhibitory action on dopamine D2 receptors. Results/outcomes: By perfusing LysoTracker fluorophore-stained cultured hippocampal neurons, we confirmed the accumulation of HAL and the non-accumulation of HAL-F. In an amphetamine hypersensitization psychosis-like model in rats, we found that subchronic intracerebroventricularly delivered HAL (0.1 mg/kg/day), but not HAL-F (0.3–1.5 mg/kg/day), attenuates psychotic-like behavior in rats. Conclusions/interpretation: These findings suggest the presynaptic accumulation of HAL may serve as an essential prerequisite for its full antipsychotic action and may explain the time course of APD action. Targeting accumulation properties of APDs may, thus, become a new strategy to improve APD action.
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Berkhout, Susan, Juveria Zaheer, and Gary Remington. "M246. DIGITAL SELF-MONITORING AND EMBODIMENT IN FIRST EPISODE PSYCHOSIS: ETHICAL CONSIDERATIONS." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S229—S230. http://dx.doi.org/10.1093/schbul/sbaa030.558.
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Abstract Background Smartphone technology has seen expanding interest across nearly all areas of medicine, including psychiatry, where app-based technologies frequently function as proxies for digitized behavioural phenotypes (Firth and Torous 2015). In the area first episode psychosis especially, there has been a rising interest in the use of digital platforms for patient self-management as well as for assessment of symptom domains (Ben-Zeev et al. 2014; Bell et al. 2018). Methods This paper discusses findings from a 3 year-long ethnographic study carried out within a first episode psychosis program in Toronto, Canada, in combination with a discourse analysis of the clinical and research literature relating to the use of self-monitoring technologies within first episode psychosis contexts. The qualitative data consists of formal and informal interviews with psychiatric service users, family members, and clinicians (n=45 interviews), in addition to observational field work within the clinical setting. Data were analyzed thematically within an interpretivist-constructivist frame, and triangulated through reflexive field notes, member-checking, and the authors’ clinical experience within the field. Themes were reviewed with senior clinicians in the first episode clinic setting as well as psychiatric service users for reliability and fidelity. Results Self-monitoring technologies are increasingly used in both research and clinical care settings, most frequently related to the management of medication side effects and the tracking of the phenomenological aspects of psychotic and psychotic-like experiences. The uptake of these technologies by psychiatric service users in this setting was varied: at times, symptom and side effect tracking faciliated conversations about uncomfortable topics such as sexual side effects of antipsychotics, while in other instances the use of self-monitoring technologies was intrusive. Challenges with self-monitoring were likely to arise when issues relevant to understanding complex phenomena such as medication adherence were prematurely narrowed or when experiential narratives were foreclosed by the structure imposed by the technologies themselves. Resistance to self-monitoring arose in novel and interesting ways. Discussion Engaging in self-monitoring, whether for side effect tracking or phenomenological analysis of moment-to-moment experiences have significant material effects on those engaged in such practices. When we consider the study findings through the lens of contemporary mental health ethics, we can appreciate how such technologies carry with them a potential for what has been termed “epistemic injustice” (Medina 2013; Fricker 2007), even at the same time as they offer potentially novel, meaningful forms of health care engagement. Grappling with this tension is of critical importance in light of the expansion of such platforms in both clinical and research environments
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Evermann, Ulrika, Simon Schmitt, Tina Meller, Julia-Katharina Pfarr, Sarah Grezellschak, and Igor Nenadić. "Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals." European Archives of Psychiatry and Clinical Neuroscience 271, no. 6 (February 2, 2021): 1111–22. http://dx.doi.org/10.1007/s00406-020-01229-5.
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AbstractIn the general population, psychosis risk phenotypes occur independently of attenuated prodromal syndromes. Neurobiological correlates of vulnerability could help to understand their meaningfulness. Interactions between the occurrence of psychotic-like experiences (PLE) and other psychological factors e.g., distress related to PLE, may distinguish psychosis-prone individuals from those without risk of future psychotic disorder. We aimed to investigate whether (a) correlates of total PLE and distress, and (b) symptom dimension-specific moderation effects exist at the brain structural level in non-help-seeking adults reporting PLE below and above the screening criterion for clinical high-risk (CHR). We obtained T1-weighted whole-brain MRI scans from 104 healthy adults from the community without psychosis CHR states for voxel-based morphometry (VBM). Brain structural associations with PLE and PLE distress were analysed with multiple linear regression models. Moderation of PLE by distress severity of two types of positive symptoms from the Prodromal Questionnaire (PQ-16) screening inventory was explored in regions-of-interest after VBM. Total PQ-16 score was positively associated with grey matter volume (GMV) in prefrontal regions, occipital fusiform and lingual gyri (p < 0.05, FDR peak-level corrected). Overall distress severity and GMV were not associated. Examination of distress severity on the positive symptom dimensions as moderators showed reduced strength of the association between PLE and rSFG volume with increased distress severity for perceptual PLE. In this study, brain structural variation was related to PLE level, but not distress severity, suggesting specificity. In healthy individuals, positive relationships between PLE and prefrontal volumes may indicate protective features, which supports the insufficiency of PLE for the prediction of CHR. Additional indicators of vulnerability, such as distress associated with perceptual PLE, change the positive brain structure relationship. Brain structural findings may strengthen clinical objectives through disentanglement of innocuous and risk-related PLE.
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Andrei, I. A., A. M. Cristache, M. E. Parfene-Banu, A. A. Frunză, M. C. Boer, M. G. Puiu, B. E. Patrichi, and M. Manea. "Acute psychosis induced by short-term treatment with methylprednisolone – a case report." European Psychiatry 33, S1 (March 2016): S626. http://dx.doi.org/10.1016/j.eurpsy.2016.01.2349.
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Steroid treatment has been widely used for immunologic and inflammatory disorders. Psychiatric symptoms are not uncommon complications of the corticosteroid treatment. Correlations between the hypothalamic-pituitary-adrenal (HPA) axis and various psychoses have been already established in the specialty literature (modified HPA activity by drugs or not, glucocorticoid receptors downregulation, reduced hippocampal volume). The prevalence of corticosteroid-induced psychotic disorders varies around 5–6%. Most corticosteroid-induced symptoms start during the first few weeks after treatment initiation, but their onset can also be in the first 3–4 days. We would like to report the case of a 30-year-old woman who was taken to the psychiatry emergency room for psychomotor agitation, auditory and visual hallucinations, and bizarre delusions, disorganized thinking and modified behavior. The patient had no personal or family history of psychiatric illness. One month earlier, she was admitted in a neurosurgery ward and underwent lumbar surgery for L4–L5 disc protrusion; at discharge, eight days later, she began treatment with methylprednisolone 80 mg/day for three days. One week later, psychotic symptoms emerged that resulted in her hospitalization in our ward for apparent steroid-induced psychosis. Treatment with risperidone (up to 6 mg/day) and diazepam (10 mg/day, rapidly discontinued) was initiated. The endocrinology examination revealed modified plasmatic cortisol. The psychosis resolved several weeks later and the patient was discharged. Psychiatric complications induced by steroids underline the role of physicians that have to educate the patients and their families about these side effects and their early recognition.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Satish Kumar Sharma and Suruchi Singh. "A Review on conceptual framework of Drug Side Effects and Pharmacoresistance in Epilepsy." International Journal of Research in Pharmaceutical Sciences 12, no. 1 (January 6, 2021): 378–83. http://dx.doi.org/10.26452/ijrps.v12i1.4030.
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Epileptic seizures in the form of involuntary body movements have made patients’ lives extremely difficult. There are mainly two types of seizures partial or focal seizure affect just one side of the brain and generalised seizures affect the whole brain of a person. The person suffers from neuro-sensory deregulation and consciousness loss, coupled with episodes of seizures. Different drug therapies have been used for epilepsy patients targeting neurotransmitters regulation mechanisms. The drug targets and mechanism of action in polytherapy remain ambiguous. However, 6 out of 10 patients quit antiepileptic drug (AED) therapy due to side effects like depression, aggression and psychosis. Several behavioral side effects make them socially awkward, due to which patients cease to continue drug therapies. The combined effect of AED side effects and resorting therapies lead to recurrent seizures which further disturb the neurotransmission on account of every seizure episode. The present review describes epilepsy in terms of clinical treatments and associated side effects. The study provides a novel conceptual loop of correlation between AED polytherapy, side effects and Pharmacoresistance. This review creates caution for clinicians to think intricately before prescribing drugs for epilepsy and ensure communication of side effects. The review opens research prospectives for drug targets to break the conceptual loop for the Pharmacoresistance. Further, this paper enhances the understanding of epilepsy and improves diseases condition.
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Mielnik, Catharine A., Kim S. Sugamori, David B. Finlay, Hayley H. A. Thorpe, Matthieu Schapira, Nirunthan Sivananthan, Chun Kit Li, et al. "A novel allosteric modulator of the cannabinoid CB1 receptor ameliorates hyperdopaminergia endophenotypes in rodent models." Neuropsychopharmacology 46, no. 2 (October 8, 2020): 413–22. http://dx.doi.org/10.1038/s41386-020-00876-5.
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AbstractThe endocannabinoid system (eCBs) encompasses the endocannabinoids, their synthetic and degradative enzymes, and cannabinoid (CB) receptors. The eCBs mediates inhibition of neurotransmitter release and acts as a major homeostatic system. Many aspects of the eCBs are altered in a number of psychiatric disorders including schizophrenia, which is characterized by dysregulation of dopaminergic signaling. The GluN1-Knockdown (GluN1KD) and Dopamine Transporter Knockout (DATKO) mice are models of hyperdopaminergia, which display abnormal psychosis-related behaviors, including hyperlocomotion and changes in pre-pulse inhibition (PPI). Here, we investigate the ability of a novel CB1 receptor (CB1R) allosteric modulator, ABM300, to ameliorate these dysregulated behaviors. ABM300 was characterized in vitro (receptor binding, β-arrestin2 recruitment, ERK1/2 phosphorylation, cAMP inhibition) and in vivo (anxiety-like behaviors, cannabimimetic effects, novel environment exploratory behavior, pre-pulse inhibition, conditioned avoidance response) to assess the effects of the compound in dysregulated behaviors within the transgenic models. In vitro, ABM300 increased CB1R agonist binding but acted as an inhibitor of CB1R agonist induced signaling, including β-arrestin2 translocation, ERK phosphorylation and cAMP inhibition. In vivo, ABM300 did not elicit anxiogenic-like or cannabimimetic effects, but it decreased novelty-induced hyperactivity, exaggerated stereotypy, and vertical exploration in both transgenic models of hyperdopaminergia, as well as normalizing PPI in DATKO mice. The data demonstrate for the first time that a CB1R allosteric modulator ameliorates the behavioral deficits in two models of increased dopamine, warranting further investigation as a potential therapeutic target in psychiatry.
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Müller, Christian, Eva-Maria Weiss, Jan Hellmann, Jana Dahlmanns, Liubov Kalinichenko, Christian Alzheimer, Stefan Löber, et al. "T215. THE ANTIPSYCHOTIC ACTION OF HALOPERIDOL IN PSYCHOTIC-LIKE RATS REQUIRES PRESYNAPTIC VESICULAR ACCUMULATION." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S314. http://dx.doi.org/10.1093/schbul/sbaa029.775.
Full textAbstract:
Abstract Background The therapeutic effects of antipsychotic drugs (APDs) are mainly attributed to their post synaptic inhibitory functions on the dopamine D2 receptor, which however, cannot explain the delayed onset of full therapeutic efficacy. It was previously shown that APDs accumulate in presynaptic vesicles during chronic treatment and are released like neurotransmitters in an activity-dependent manner triggering an auto-inhibitory feedback mechanism. Although closely mirroring therapeutic action onset, the functional consequence of the APD accumulation remained unclear. Here we show that the accumulation of the APD haloperidol (HAL) is required for full therapeutic action in psychotic-like rats. Methods We designed a haloperidol (HAL) analogue compound (HAL-F), which lacks the accumulation property of HAL, but retains its antagonist action at dopamine D2 receptors. Results By perfusing lysotracker fluorophore-stained cultured hippocampal neurons, we confirmed the accumulation of HAL and the non-accumulation of HAL-F. In an AMPH-hypersensitization psychosis-like model in rats, we found that subchronic i.c.v. delivered HAL, but not HAL-F attenuates psychotic-like behavior in rats in an amphetamine-induced hyperlocomotion test and the a pre-puls inhibition of an acustic startle response. Discussion These findings suggest the presynaptic accumulation of HAL as an essential prerequisite for its full antipsychotic action and may better explain the time course of APD action. Targeting accumulation properties of APDs may, thus, become a new strategy to improve APD action.