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Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use.
We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case–control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis.
Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset <18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42).
Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.
Cannabis use disorder is associated with an earlier age at onset and a more severe outcome of schizophrenia spectrum disorders. The role of cannabis use before the onset of illness (premorbid cannabis use) has not been fully investigated. We here examined how amount and type of premorbid cannabis use was associated with the later course of illness including current substance use, symptoms and level of functioning in schizophrenia spectrum disorder.
We used a naturalistic sample of patients with DSM-IV schizophrenia spectrum disorders with a comprehensive history of illness and substance use. Data on premorbid substance use was obtained from comprehensive self-report. The relationship to outcome was investigated using regression models that included current substance use and premorbid functioning.
Pre-schizophrenia cannabis use was significantly associated with more severe psychotic symptoms and impaired functioning. Higher levels of premorbid cannabis use were associated with higher levels of current psychotic symptoms. These associations were independent of current substance use and premorbid functioning. Early use of cannabis (age <17 years) was associated with earlier age at onset of psychosis, independently of potential confounders.
Pre-psychosis cannabis use affects illness outcome in schizophrenia spectrum disorders, and is associated with lower age at onset of psychosis. These findings of independent negative effects of premorbid cannabis use in schizophrenia suggest that a limitation of the general use of cannabis may have beneficial health effects.
Previous studies of bipolar disorders indicate that childhood abuse and substance abuse are associated with the disorder. Whether both influence the clinical picture, or if one is mediating the association of the other, has not previously been investigated.
A total of 587 patients with bipolar disorders were recruited from Norway and France. A history of childhood abuse was obtained using the Childhood Trauma Questionnaire. Diagnosis and clinical variables, including substance abuse, were based on structured clinical interviews (Structured Clinical Interview for DSM-IV Axis I disorders or French version of the Diagnostic Interview for Genetic Studies).
Cannabis abuse was significantly associated with childhood abuse, specifically emotional and sexual abuse (χ2 = 8.63, p = 0.003 and χ2 = 7.55, p = 0.006, respectively). Cannabis abuse was significantly associated with earlier onset of the illness (z = −4.17, p < 0.001), lifetime history of at least one suicide attempt (χ2 = 11.16, p = 0.001) and a trend for rapid cycling (χ2 = 3.45, p = 0.06). Alcohol dependence was associated with suicide attempt (χ2 = 10.28, p = 0.001), but not with age at onset or rapid cycling. After correcting for possible confounders and multiple testing, a trend was observed for an interaction between cannabis abuse and childhood abuse and suicide attempt (logistic regression: r2 = 0.06, p = 0.039). Significant additive effects were also observed between cannabis abuse and childhood abuse on earlier age at onset (p < 0.001), increased rapid cycling and suicide attempt (logistic regression: r2 = 0.03–0.04, p < 0.001). No mediation effects were observed; childhood abuse and cannabis abuse were independently associated with the disorder.
Our study is the first to demonstrate significant additive effects, but no mediation effects, between childhood abuse and cannabis abuse on increased clinical expressions of bipolar disorders.
Cannabis use is associated with altered neurocognitive functioning in severe mental disorders, but data are still inconclusive and there are no studies of bipolar disorder. The aim of this study was to investigate the association between cannabis use and neurocognition in bipolar disorder compared with schizophrenia in a naturalistic setting.
A total of 133 patients with bipolar disorder and 140 patients with schizophrenia underwent neuropsychological assessments and clinical characterization including measures of substance use. Relationships between cannabis users and neurocognitive function were explored in the two diagnostic groups. Possible interactions between diagnosis and cannabis use were investigated, and findings were controlled for possible confounders.
In bipolar disorder subjects, cannabis use was associated with better neurocognitive function, but the opposite was the case for the schizophrenia subjects. There was a statistically significant interaction effect of diagnosis and cannabis use on focused attention (p=0.019), executive functioning (verbal fluency – set shifting) (p=0.009), logical memory-learning (p=0.007) and on logical memory-recall (p=0.004). These differences in neurocognitive function could not be explained by putative confounders.
The findings suggest that cannabis use may be related to improved neurocognition in bipolar disorder and compromised neurocognition in schizophrenia. The results need to be replicated in independent samples, and may suggest different underlying disease mechanisms in the two disorders.
Schizophrenia and bipolar disorder have partly overlapping clinical profiles, which include an over-representation of substance-use behaviour. There are few previous studies directly comparing substance-use patterns in the two disorders. The objective of the present study was to compare the prevalence of substance use in schizophrenia and bipolar disorder, and investigate possible differences in pattern and frequency of use.
A total of 336 patients with schizophrenia or bipolar spectrum disorder from a catchment area-based hospital service were included in a cross-sectional study. In addition to thorough clinical assessments, patients were interviewed about drug-use history, habits and patterns of use. The prevalence and drug-use patterns were compared between groups.
Patients with bipolar disorder had higher rates of alcohol consumption, while schizophrenia patients more often used centrally stimulating substances, had more frequent use of non-alcoholic drugs and more often used more than one non-alcoholic drug. Single use of cannabis was more frequent in bipolar disorder.
The present study showed diagnosis-specific patterns of substance use in severe mental disorder. This suggests a need for more disease-specific treatment strategies, and indicates that substance use may be an important factor in studies of overlapping disease mechanisms.
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