Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met lit.opg. en samenvatting in het Nederlands.

Proefschrift Rijksuniversiteit Limburg, Maastricht. / Met lit. opg., bibliogr. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Auteursnaam op omslag: Sandra Escher. Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Objective: To investigate the relation between cannabis use and psychotic symptoms in individuals with above average predisposition for psychosis who first used cannabis during adolescence. Design: Analysis of prospective data from a population based sample. Assessment of substance use, predisposition for psychosis, and psychotic symptoms was based on standardised personal interviews at baseline and at follow up four years later. Participants: 2437 young people (aged 14 to 24 years) with and without predisposition for psychosis. Main outcome measure: Psychotic symptoms at follow up as a function of cannabis use and predisposition for psychosis at baseline. Results: After adjustment for age, sex, socioeconomic status, urbanicity, childhood trauma, predisposition for psychosis at baseline, and use of other drugs, tobacco, and alcohol, cannabis use at baseline increased the cumulative incidence of psychotic symptoms at follow up four years later (adjusted odds ratio 1.67, 95% confidence interval 1.13 to 2.46). The effect of cannabis use was much stronger in those with any predisposition for psychosis at baseline (23.8% adjusted difference in risk, 95% confidence interval 7.9 to 39.7, P = 0.003) than in those without (5.6%, 0.4 to 10.8, P = 0.033). The risk difference in the “predisposition” group was significantly greater than the risk difference in the “no predisposition” group (test for interaction 18.2%, 1.6 to 34.8, P = 0.032). There was a dose-response relation with increasing frequency of cannabis use. Predisposition for psychosis at baseline did not significantly predict cannabis use four years later (adjusted odds ratio 1.42, 95% confidence interval 0.88 to 2.31). Conclusion: Cannabis use moderately increases the risk of psychotic symptoms in young people but has a much stronger effect in those with evidence of predisposition for psychosis.

Evidence from clinical patient populations indicates that affective dysregulation is strongly associated with reality distortion, suggesting that a process of misassignment of emotional salience may underlie this connection. To examine this in more detail without clinical confounds, affective regulation-reality distortion relationships, and their clinical relevance, were examined in a German prospective cohort community study. A cohort of 2524 adolescents and young adults aged 14–24 years at baseline was examined by experienced psychologists. Presence of psychotic experiences and (hypo)manic and depressive symptoms was assessed at 2 time points (3.5 and up to 10 years after baseline) using the Munich-Composite International Diagnostic Interview. Associations were tested between level of affective dysregulation on the one hand and incidence of psychotic experiences, persistence of these experiences, and psychotic Impairment on the other. Most psychotic experiences occurred in a context of affective dysregulation, and bidirectional dose-response was apparent with greater level of both affective dysregulation and psychotic experiences. Persistence of psychotic experiences was progressively more likely with greater level of (hypo)manic symptoms (odds ratio [OR] trend = 1.51, P < .001) and depressive symptoms (OR trend = 1.15, P = .012). Similarly, psychotic experiences of clinical relevance were progressively more likely to occur with greater level of affective dysregulation (depressive symptoms: OR trend = 1.28, P = .002; (hypo)manic symptoms: OR trend = 1.37, P = .036). Correlated genetic liabilities underlying affective and nonaffective psychotic syndromes may be expressed as correlated dimensions in the general population. Also, affective dysregulation may contribute causally to the persistence and clinical relevance of reality distortion, possibly by facilitating a mechanism of aberrant salience attribution.

Background: Schizophrenia first appears in adolescence, in boys at an earlier age than girls. The interpretation of this key epidemiological finding crucially depends on whether similar age-related sex differences exist in the expression of associated, subclinical psychosis-like experiences. Methods: Findings are based on a population sample of 2548 adolescents and young adults aged 17–28. Subjects were assessed with the core psychosis sections on delusions and hallucinations of the Munich- Composite International Diagnostic Interview. Results: The risk of subclinical psychotic experiences was significantly higher for males in the younger half of the cohort (17–21 years), but similar in the older half (22–28 years). Conclusions: These findings suggest that normal maturational changes in adolescence with differential age of onset in boys and girls cause the expression of psychosis, the extreme of which is schizophrenia.

Background: It is commonly assumed that there are clear lines of demarcation between anxiety and depressive disorders on the one hand and psychosis on the other. Recent evidence, however, suggests that this principle may be in need of updating. Methods: Depressive and/or anxiety disorders, with no previous history of psychotic disorder, were examined for the presence of psychotic symptoms in a representative community sample of adolescents and young adults (Early Developmental Stages of Psychopathology study; n=3021). Associations and consequences of psychotic symptomatology in the course of these disorders were examined in terms of demographic distribution, illness severity, onset of service use, and risk factors. Results: Around 27% of those with disorders of anxiety and depression displayed one or more psychotic symptoms, vs 14% in those without these disorders (OR 2.23, 95% CI 1.89–2.66, P < .001). Presence as compared with nonpresence of psychotic symptomatology was associated with younger age (P < .0001), male sex (P < .0058), and poorer illness course (P < .0002). In addition, there was greater persistence of schizotypal (P < .0001) and negative symptoms (P < .0170), more observable illness behavior (P < .0001), greater likelihood of service use (P < .0069), as well as more evidence of familial liability for mental illness (P < .0100), exposure to trauma (P < .0150), recent and more distant life events (P < .0006–.0244), cannabis use (P < .0009), and any drug use (P < .0008). Conclusion: Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.

Cannabis use is considered a component cause of psychotic disorder interacting with genetic and environmental risk factors in increasing psychosis risk (Henquet et al., 2008). Recently, two cross-sectional and one prospective study provided evidence that cannabis use interacts additively with trauma to increase psychosis risk (Houston et al., 2008, Harley et al., 2010 and Konings et al., 2011). In an attempt at further replication, we examined prospective data from the German Early Developmental Stages of Psychopathology (EDSP) study (Wittchen et al., 1998b and Lieb et al., 2000).