Effects of cannabis use on age at onset in schizophrenia and bipolar disorder

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Abstract

Background

Cannabis use may decrease age at onset in both schizophrenia and bipolar disorder, given the evidence for substantial phenotypic and genetic overlap between both disorders.

Methods

766 patients, aged 16 to 65 years, were assessed with the Composite International Diagnostic Interview (CIDI) for substance abuse/use. 676 subjects were diagnosed with schizophrenia and 90 subjects with bipolar disorder. The influence of cannabis use on age at onset in both schizophrenia and bipolar disorder was examined using regression analysis.

Results

Cannabis and other substance use was more frequent in patients with schizophrenia compared to the bipolar group. Both cannabis use and a schizophrenia diagnosis predicted earlier age at onset. There was a significant interaction between cannabis use and diagnosis, cannabis having a greater effect in bipolar patients. Age at onset in users of cannabis was comparable in both diagnostic groups whereas bipolar non-users were significantly older than schizophrenia non-users at onset.

Conclusion

Cannabis use may decrease age at onset in both schizophrenia and bipolar patients and reduce the effect of diagnosis. This is consistent with the view that cannabis use may unmask a pre-existing genetic liability that is partly shared between patients with schizophrenia and bipolar disorder.

Introduction

Numerous studies indicated that substance abuse, and in particular the use of cannabis, is highly prevalent in patients with schizophrenia (Andreasson et al., 1987, Dalmau et al., 1999, Degenhardt and Hall, 2001, Dixon, 1999, Fergusson et al., 2006, Henquet et al., 2005, Fowler et al., 1998, Hambrecht and Hafner, 2000, Moore et al., 2007, Mueser et al., 2000, Thornicroft, 1990) as well as in patients with bipolar disorder (Fogarty et al., 1994, Regier et al., 1990, Strakowski et al., 1998a, Strakowski et al., 1998b, Sherwood Brown et al., 2001, Strakowski et al., 2000, Verdoux et al., 1996).

Schizophrenia patients using substances experience more psychotic symptoms, have more frequent visits to emergency rooms, have decreased adherence to treatment, more cognitive deficits (Dixon, 1999, Green, 2005, Green et al., 2005, Mueser et al., 1992, Owen et al., 1996, Swartz and Lurigio, 2006), more frequent and earlier relapses (Brady et al., 1990, Drake et al., 1989, Linszen et al., 1994), rehospitalisation (Caspari, 1999, Drake et al., 1989, Drake and Brunette, 1998, Gupta et al., 1996, Mathers and Ghodse, 1992, Negrete et al., 1986, Richard et al., 1985), violent behaviour (Abram and Teplin, 1991, Swanson et al., 1990), victimization (Goodman et al., 2001, Hiday et al., 1999), homelessness (Caton et al., 1994), an increased risk of HIV, hepatitis B and C infections (Cournos and McKinnon, 1997, Rosenberg et al., 2001), higher suicide risk (Green et al., 2002, Potvin et al., 2003), lower educational attainment (Kavanagh et al., 2004, Mueser et al., 1992, Rabinowitz et al., 1998, Sevy et al., 2001, Swartz et al., 2008), and an overall worse prognosis (Barnes et al., 2006, Green et al., 2004). In bipolar patients as well, treatment response and clinical outcome are worse in patients with co-morbid substance abuse (Goldberg et al., 1999, Strakowski et al., 1998b, Tohen et al., 1990, van Rossum et al., 2009).

In addition to influencing course and outcome, substance abuse may also influence age at onset of both disorders. Age at onset may be an informative phenotype (DeLisi, 1992) given a possible association with underlying genetic liability to schizophrenia (Byrne et al., 2002) and high heritability in patients with schizophrenia (Allan et al., 2009). Furthermore, age of onset was suggested to be clinically relevant because of the increasing importance to identify predictors of transition to overt psychosis in individuals with a so called at-risk mental state (Compton et al., 2009). Studies have also demonstrated a prognostic effect of age at onset on both acute treatment response (Crespo-Facorro et al., 2007) as well as long-term outcome in patients with schizophrenia (McGrath et al., 2010, Rabinowitz et al., 2006).

In schizophrenia, the results of various studies investigating the effect of cannabis use on age at onset have not always been consistent. Some studies found no significant association between cannabis use and age at onset (Cantor-Graae et al., 2001, Sevy et al., 2001), some have found a reduction in age at onset for female but not for male patients (Rabinowitz et al., 1998) while the reverse, namely a reduction in age of onset in male but not female patients was reported by Veen et al. (2004). Other studies also reported an earlier age at onset in cannabis-using patients but not all of these studies corrected for gender differences, even though gender differences in age at onset were often reported (Addington and Addington, 2001, Gonzalez-Pinto et al., 2008, Hambrecht and Hafner, 1996), but not always (Kohler et al., 2007, Sugranyes et al., 2009). A meta-analysis of recent studies showed that cannabis use disorders were more common in younger, first episode, male schizophrenia patients (Koskinen et al., 2009).

In bipolar disorder, there is evidence that in many patients substance abuse precedes the onset of bipolar disorder (Strakowski et al., 1998b) and it has been suggested that substance abuse may contribute to affective deregulation and may hence increase the risk for development of bipolar disorder. An association between substance abuse and an earlier age at onset of bipolar disorder is however not consistently observed. An association between substance abuse and age at onset was observed in some (Brady and Lydiard, 1992, Sonne et al., 1994, Tien and Anthony, 1990), but not all studies (Strakowski et al., 1996, Escamilla et al., 2002). In most of these studies however, it was not possible to disentangle the effect of specific substances since different substances were often combined into one category.

Substantial evidence has now convincingly shown phenotypic, neurobiological and genetic overlap between schizophrenia and bipolar disorder (Kerr and McClelland, 1991, Lichtenstein et al., 2009, Moskvina et al., 2009, Purcell et al., 2009, Van Snellenberg and de Candia, 2009). Therefore, it may be hypothesized that cannabis use decreases age at onset in both schizophrenia and bipolar disorder, as was suggested in a recent study investigating a sample of 141 patients with schizophrenia or schizoaffective disorder and 92 patients with bipolar disorder (Ongur et al., 2009). Öngur and colleagues found that lifetime cannabis abuse/dependence was associated on average with a 3-year earlier age at onset. These authors did not observe a significant association with either psychiatric diagnosis or gender. Whether the association between cannabis abuse/dependence and age at onset differed as a function of psychiatric diagnosis and/or gender was not investigated in this study even though such a differential association may be conceivable.

The current study therefore aimed to investigate whether the frequently reported association between cannabis use and age of onset differed as a function of psychiatric diagnosis. Because findings regarding the relationship between cannabis use and age of onset in male en female patients were inconsistent, the possibility of a gender-specific association between cannabis use and age at onset was also studied.

Section snippets

Subjects

Eligible patients were recruited through the outpatient and inpatient units at the University Psychiatric Centre and affiliate services, during the period 1.1.2003 to 31.12.2006. Diagnosis was established by the treating psychiatrist using DSM-IV criteria. Not diagnosis at first episode but the most recent diagnosis as established by the treating psychiatrist was used since this diagnosis takes advantage of the information gathered over the course of the illness and is most likely to avoid

Results

Table 1 presents basic demographic and clinical data of the study population. The sample consisted of 766 subjects (61.6% males and 38.4% females). All subjects were between 16 and 65 years (mean age 38.5, SD = 12). 88.3% of patients were diagnosed with schizophrenia or schizoaffective disorder, the remaining 11.7% suffered from bipolar disorder. Because no significant differences in age at first admission between schizophrenic and schizoaffective patients were found these patients were combined

Discussion

Our study in a large sample of patients with schizophrenia and bipolar disorder with psychotic features confirms the high rates of cannabis use in these patient groups. Rates of cannabis use were significantly higher in patients with schizophrenia compared to a bipolar sample. Overall the intensity and frequency did not differ in users between the two diagnostic groups.

Our results suggest that cannabis use is associated with a reduction in age at onset in both schizophrenic and bipolar

Conclusion

The high rates of substance and cannabis use, especially in young patients with schizophrenia, but also in patients with bipolar disorder are important in the clinical care of patients because of the impact on age of onset and its influence on the course of the disorder.

Role of Funding Source

None.

Contributors

M De Hert wrote the first draft of this paper and the consecutive drafts were reviewed by all authors. T Jendricko, T Franic and D Vidivoc did the literature review. Study design: M De Hert, R van Winkel and J Peuskens. M Wampers performed the statistical analysis. Data collection was mainly performed by N De Vriendt and K Sweers.

Conflict of Interest

None of the authors have a conflict of interest relevant to this paper.

Acknowledgements

The authors would like to thank the patients who participated in the study.

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