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INTRODUCTION: 18q deletion syndrome is a rare genetic disorder characterized by various neurodevelopmental anomalies and medical issues. Although the occurrence of psychosis has been reported in a small number of cases, details regarding the nature of such symptoms and their response to treatment have not been described. CASE PRESENTATION: We describe a 31-year-old male with a history of speech delays, autistic features, a tethered spinal cord, bilateral vertical talus, subaortic stenosis and aortic regurgitation, recurrent otitis media, mild hearing loss, and hypospadias, who experienced a first episode of psychosis in his late 20s. His psychotic symptoms included auditory hallucinations, various delusions, and disorganization of thought. Although his presentation is atypical in certain ways (e.g., exhibiting highly fluctuant symptoms), he nonetheless meets criteria for schizophrenia. Given his overall clinical picture, chromosomal microarray analysis was completed, which revealed a 19.78 Mb deletion at 18q21.32 from nucleotide 58,226,713 to 78,015,180 (GRCh37). Despite exhibiting a somewhat idiosyncratic response to numerous antipsychotic medications, he eventually achieved partial remission of symptoms with improved insight on relatively low dose oral aripiprazole therapy. CONCLUSION: This is the first in-depth description of 18q deletion syndrome-associated schizophrenia. While our patient's atypical presentation and idiosyncratic response to treatment may be mediated by his comorbid diagnosis of autism, his unusual psychiatric phenotype may alternatively be directly related to his underlying genetic disorder. The description of additional cases in the future will hopefully help clarify matters further.
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One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p < 0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
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Antipsicóticos , Clozapina , Miocardite , Esquizofrenia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Estudo de Associação Genômica Ampla , Humanos , Miocardite/induzido quimicamente , Miocardite/tratamento farmacológico , Miocardite/genética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genéticaRESUMO
A position statement developed by the Canadian Psychiatric Association's (CPA) Research Committee and approved by the CPA's Board of Directors on May 13, 2020.
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Canabinoides , Transtornos Mentais , Psiquiatria , Adulto , Canadá , Humanos , Transtornos Mentais/tratamento farmacológico , Sociedades MédicasRESUMO
OBJECTIVE: The Coordinators of Psychiatric Education (COPE) Residency In-Training Exam is a formative exam for Canadian psychiatric residents that was reconstructed using assessment best practices. An assessment of psychometric properties was subsequently performed on the exam to ensure preliminary validity and reliability. METHODS: An exam blueprint was developed based on the 2007 Royal College objectives for psychiatric training. A minimum pass level was established using a modified Angoff method. The exam was administered to all Canadian psychiatric residents in postgraduate years 2 to 5 with test reliability (Cronbach alpha) and item analysis performed. Exam validity was assessed through blueprint adherence and cross-year resident performance analysis. RESULTS: Four hundred two exams were suitable for analysis. The overall mean score for all residents was 69.6% (SD=8.5) with significant differences in total scores between each of the postgraduate year groups, with consistently better performance with increasing time in residency. Cronbach alpha was 0.79. CONCLUSION: The present study provides preliminary support that the reconstructed COPE Residency In-Training Exam demonstrates adequate reliability and validity, including showing the capacity to discriminate between levels of training.
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Internato e Residência/organização & administração , Psiquiatria/educação , Psiquiatria/organização & administração , Avaliação Educacional , Humanos , Psicometria/métodosRESUMO
BACKGROUND: Previous studies using functional magnetic resonance imaging (fMRI) have identified differential brain activity in healthy subjects performing gambling tasks and in pathological gambling (PG) subjects when exposed to motivational and emotional predecessors for gambling as well as during gambling or response inhibition tasks. The goal of the present study was to determine if PG subjects exhibit differential brain activity when exposed to visual gambling cues. METHODS: Ten male DSM-IV-TR PG subjects and 10 matched healthy control subjects underwent fMRI during visual presentations of gambling-related video alternating with video of nature scenes. RESULTS: Pathological gambling subjects and control subjects exhibited overlap in areas of brain activity in response to the visual gambling cues; however, compared with control subjects, PG subjects exhibited significantly greater activity in the right dorsolateral prefrontal cortex (DLPFC), including the inferior and medial frontal gyri, the right parahippocampal gyrus, and left occipital cortex, including the fusiform gyrus. Pathological gambling subjects also reported a significant increase in mean craving for gambling after the study. Post hoc analyses revealed a dissociation in visual processing stream (dorsal vs. ventral) activation by subject group and cue type. CONCLUSIONS: These findings may represent a component of cue-induced craving for gambling or conditioned behavior that could underlie pathological gambling.