A controlled family study of cannabis users with and without psychosis.

BACKGROUND: Cannabis is one of the most highly abused illicit drugs in the world. Several studies suggest a link between adolescent cannabis use and schizophrenia. An understanding of this link would have significant implications for legalization of cannabis and its medicinal value. The present study aims to determine whether familial morbid risk for schizophrenia is the crucial factor that underlies the association of adolescent cannabis use with the development of schizophrenia. METHODS: Consecutively obtained probands were recruited into four samples: sample 1: 87 non-psychotic controls with no drug use; sample 2: 84 non-psychotic controls with cannabis use; sample 3: 32 patients with a schizophrenia spectrum psychosis with no drug use; sample 4: 76 patients with schizophrenia spectrum psychosis with cannabis use. All cannabis using subjects used this drug during adolescence, and no other substance, with the exception of alcohol. Structured interviews of probands and family informants were used to obtain diagnostic information about probands and all their known relatives. RESULTS: There was an increased morbid risk for schizophrenia in relatives of the cannabis using and non-using patient samples compared with their respective non-psychotic control samples (p=.002, p<.001 respectively). There was no significant difference in morbid risk for schizophrenia between relatives of the patients who use or do not use cannabis (p=.43). CONCLUSIONS: The results of the current study suggest that having an increased familial morbid risk for schizophrenia may be the underlying basis for schizophrenia in cannabis users and not cannabis use by itself.

Alterations in brain structures underlying language function in young adults at high familial risk for schizophrenia.

INTRODUCTION: Neuroanatomical and cognitive alterations typical of schizophrenia (SZ) patients are observed to a lesser extent in their adolescent and adult first-degree relatives, likely reflecting neurodevelopmental abnormalities associated with genetic risk for the illness. The anatomical pathways for language are hypothesized to be abnormal and to underlie the positive symptoms of schizophrenia. Examining non-psychotic relatives at high familial risk (FHR) for schizophrenia may clarify if these deficits represent trait markers associated with genetic vulnerability, rather than specific markers resulting from the pathological process underlying schizophrenia. METHODS: T1 MRI scans from a 3T Siemens scanner of young adult FHR subjects (N=46) and controls with no family history of illness (i.e. at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. We explored volumetric and lateralization alterations in regions associated with language processing. An extensive neuropsychological battery of language measures was administered. RESULTS: No significant differences were observed between groups on any language measures. Controlling intracranial volume, significantly smaller left pars triangularis (PT) (p<0.01) and right pars orbitalis (PO) (p<0.01) volumes and reversal of the L>R pars orbitalis (p<0.001) lateralization were observed in FHR subjects. In addition, the L pars triangularis and R pars orbitalis correlated with performance on tests of linguistic function in the FHR group. CONCLUSIONS: Reduced volume and reversed structural asymmetry in language-related regions hypothesized to be altered in SZ are also found in first degree relatives at FHR, despite normal language performance. To clarify if these findings are endophenotypes for Sz, future studies would need to be performed of ill and well family members no longer within the age range of risk for illness to show these deficits segregate with schizophrenia within families. Moreover, measures of complex language need to be studied to determine if FHR individuals manifest impairments in some aspects of language function.

Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis.

INTRODUCTION: Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs. METHODS: Fifty-seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables. RESULTS: After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (ß=0.4, 95% CI=0.1-0.7, p=0.004) and age at first hospitalization (ß=0.4, 95% CI=0.1-0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0±4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization. CONCLUSION: Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time.

Correlates to the variable effects of cannabis in young adults: a preliminary study.

BACKGROUND: Cannabis use can frequently have adverse affects in those that use it and these can be amplified by various characteristics of an individual, from demographic and environmental variations to familial predisposition for mental illnesses. METHODS: The current study of 100 individuals, who were cannabis users during their adolescence and may still be users, was a survey of the self perceived effects of cannabis and their correlates. A reliable family member was also interviewed for determination of family history of various major mental illnesses and substance use. RESULTS: As many as 40% of cannabis users had paranoid feelings (suspiciousness) when using cannabis, although the most frequent effect was feeling relaxed (46%). Having a familial background for mental illnesses such as depression or schizophrenia did not determine the effects of cannabis nor its pattern of use, although the number of subjects with such a history was small. An age at which an individual began using cannabis did have an effect on how heavily it was used and the heavier the cannabis use, the more likely the individual was also to have had psychotic symptoms after use. There were no sex differences in effects of cannabis. These results are tempered by the reliance on self-report for many of the variables ascertained. CONCLUSION: Cannabis can frequently have negative effects in its users, which can be amplified by certain demographic and/or psychosocial factors. Thus, users with a specific profile may be at a higher risk of unpleasant effects from cannabis use and caution should be noted when cannabis is administered to young people for medicinal purposes.