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Cannabis, Schizophrenia Risk and Genetics: A Case Report of a Patient With Homozygous Valine Catechol-O-Methyltransferase Polymorphism.

ABSTRACT: The question of whether cannabis can trigger schizophrenia continues to be a subject of interest. There has been an increasing focus on identifying potential genetic factors that may predispose cannabis users to develop schizophrenia. One such gene identified in many studies codes for a catechol-O-methyltransferase (COMT) enzyme polymorphism. These studies, however, are limited by the inclusion of patients displaying psychotic symptoms during cannabis intoxication and those who continue to display psychotic symptoms after its cessation. The latter is of interest in truly understanding the risk of cannabis triggering schizophrenia and more studies are needed to clarify the potential relationship. We present the case of a 24-year-old female who presented with psychotic symptoms and was diagnosed with schizophrenia after extensive cannabis use. In addition, she had a homozygous valine COMT polymorphism, a genetic variant thought to be associated with a predisposition for schizophrenia in cannabis users. We discuss the significance of our findings in understanding the relationship between cannabis use and the development of schizophrenia in genetically predisposed individuals.

SUBMITTER: Grechuk K

PROVIDER: S-EPMC8286638 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response.MethodsSearches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study's original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model.ResultsTen studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal=1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P=.039, ORMet/Met=1.37, 95% CI: 1.02-1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P=.030, SMD=0.24, 95% CI: 0.024-0.46). Posthoc analyses on patients treated with atypical antipsychotics (n=1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P=.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155) (P=.65).ConclusionsOur findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics.

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Cannabis, Schizophrenia Risk and Genetics: A Case Report of a Patient With Homozygous Valine Catechol-O-Methyltransferase Polymorphism.

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