Predisposing Factors and Clinical Presentations of Primary and Drug-Induced Chronic Psychoses

Psychosis is an etiologically complex syndrome that arises from the interaction of a range of factors. The most commonly studied disorder regarding constitutional vulnerability to psychosis is schizophrenia. Two major theories of schizophrenia are respectively, the dopamine hypothesis and the neurodevelopmental hypothesis. The classical neurodevelopmental hypothesis has been recently modified to include the pathogenic effects of psychostimulants and cannabis abuse. Methamphetamine (MAMP) use has been reported to result in psychotic symptoms lasting more than several months. The prolonged psychotic symptoms in MAMP psychosis are hypothesized by some investigators to generally represent a triggering or unmasking of vulnerability to a psychotic state or latent schizophrenia. In the past 10 years, we have conducted a series of studies that investigated predisposing factors to MAMP-induced psychosis. By this study, we have published a series of reports describing our findings in clinical characteristics, premorbid characteristics, familial psychosis morbid risks and genetic associations among MAMP abusers, and established collaborations internationally with several research groups. Our studies showed that the relatives of MAMP users with a lifetime diagnosis ofMAMP psychosis had a significantly higher morbid risk for schizophrenia than the relatives of those probands who never became psychotic. Furthermore, the morbid risk for schizophrenia in the relatives of the subjects with a prolongedMAMP psychosis was higher than in the relatives of those users with a brief MAMP psychosis. Compared to those MAMP abusers without psychosis, the MAMP abusers with psychosis had significantly more premorbid schizoid/schizotypal personality trait. Our previous work on MAMP psychosis has been frequently cited in research papers and review articles, and has been suggested to be influential in the fields of comorbidity of substance abuse, etiological models of schizophrenia, and the nosology of prolonged or chronic substance-induced psychosis. However, the issue of a prolonged drug-induced psychosis continues to remain a contentious issue. This proposed study will be the largest longitudinal study of prolonged MAMP-induced psychosis, and will be the largest study that compares this group of patients with carefully matched schizophrenics. The aims of this investigation are 1) to understand the role of substance use in the development of chronic psychotic disorders, and its interaction with genes, family morbid risks for psychosis and premorbid function; 2) to characterize clinical presentations of MAMP-induced chronic psychosis, including psychotic dimensions and neurocognitive performance. We aim to longitudinally follow up 100 cases with chronic psychosis after MAMP use recruited previously since 10 years ago. We will characterize their clinical presentations and investigate their predisposing factors by comparing to 100 patients with schizophrenia or schizoaffective disorder after matching in age, sex, subtype of psychosis and duration of psychosis. We will compare the neurocognitive performance using the Brief Assessment of Cognition in Schizophrenia between these two groups. We will also compare genetic polymorphisms of susceptibility genes that have recently been reported to be associated with schizophrenia, such as neuregulin, dysbindin, Disrupted in Schizophrenia 1 (DISC1) and catechol-O-methyltransferase (COMT) genes between these two groups and 200 MAMP abusers without psychosis which were collected in our previous studies.

Project ID:PC9808-0544
External Project ID:NSC98-2314-B182-023-MY3