Do cannabis and urbanicity co-participate in causing psychosis? Evidence from a 10-year follow-up cohort study

Background Cannabis use is considered a component cause of psychotic illness, interacting with genetic and other environmental risk factors. Little is known, however, about these putative interactions. The present study investigated whether an urban environment plays a role in moderating the effects of adolescent cannabis use on psychosis risk. Method Prospective data (n=1923, aged 14-24 years at baseline) from the longitudinal population-based German Early Developmental Stages of Psychopathology cohort study were analysed. Urbanicity was assessed at baseline and defined as living in the city of Munich (1562 persons per km2; 4061 individuals per square mile) or in the rural surroundings (213 persons per km2; 553 individuals per square mile). Cannabis use and psychotic symptoms were assessed three times over a 10-year follow-up period using the Munich version of the Composite International Diagnostic Interview. Results Analyses revealed a significant interaction between cannabis and urbanicity [10.9% adjusted difference in risk, 95% confidence interval (CI) 3.2-18.6, p=0.005]. The effect of cannabis use on follow-up incident psychotic symptoms was much stronger in individuals who grew up in an urban environment (adjusted risk difference 6.8%, 95% CI 1.0-12.5, p=0.021) compared with individuals from rural surroundings (adjusted risk difference −4.1%, 95% CI −9.8 to 1.6, p=0.159). The statistical interaction was compatible with substantial underlying biological synergism. Conclusions Exposure to environmental influences associated with urban upbringing may increase vulnerability to the psychotomimetic effects of cannabis use later in lif

Prevalence and severity of mental disorders in military personnel: a standardised comparison with civilians

Aims. Provision and need for mental health services among military personnel are a major concern across nations. Two recent comparisons suggest higher rates of mental disorders in US and UK military personnel compared with civilians. However, these findings may not apply to other nations. Previous studies have focused on the overall effects of military service rather than the separate effects of military service and deployment. This study compared German military personnel with and without a history of deployment to sociodemographically matched civilians regarding prevalence and severity of 12-month DSM-IV mental disorders. Method. 1439 deployed soldiers (DS), 779 never deployed soldiers (NS) and 1023 civilians were assessed with an adapted version of the Munich Composite International Diagnostic interview across the same timeframe. Data were weighted using propensity score methodology to assure comparability of the three samples. Results. Compared with adjusted civilians, the prevalence of any 12-month disorder was lower in NS (OR: 0.7, 95% CI: 0.5–0.99) and did not differ in DS. Significant differences between military personnel and civilians regarding prevalence and severity of individual diagnoses were only apparent for alcohol (DS: OR: 0.3, 95% CI: 0.1–0.6; NS: OR: 0.2, 95% CI: 0.1–0.6) and nicotine dependence (DS: OR: 0.5, 95% CI: 0.3–0.6; NS: OR: 0.5, 95% CI: 0.3–0.7) with lower values in both military samples. Elevated rates of panic/agoraphobia (OR: 2.7, 95% CI: 1.4–5.3) and posttraumatic stress disorder (OR: 3.2, 95% CI: 1.3–8.0) were observed in DS with high combat exposure compared with civilians. Conclusions. Rates and severity of mental disorders in the German military are comparable with civilians for internalising and lower for substance use disorders. A higher risk of some disorders is reduced to DS with high combat exposure. This finding has implications for mental health service provision and the need for targeted interventions. Differences to previous US and UK studies that suggest an overall higher prevalence in military personnel might result from divergent study methods, deployment characteristics, military structures and occupational factors. Some of these factors might yield valuable targets to improve military mental health

The role of mental disorders in the risk and speed of transition to alcohol use disorders among community youth

Background Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition. Method A total of 3021 community subjects (97.7% lifetime AU) aged 14–24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI. Results Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition. Conclusions Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD

Treating treatment-resistant patients with panic disorder and agoraphobia: A randomized controlled switching trial

Background: Nonresponsiveness to therapy is generally acknowledged, but only a few studies have tested switching to psychotherapy. This study is one of the first to examine the malleability of treatment-resistant patients using acceptance and commitment therapy (ACT). Methods: This was a randomized controlled trial that included 43 patients diagnosed with primary panic disorder and/or agoraphobia (PD/A) with prior unsuccessful state-of-the-art treatment (mean number of previous sessions = 42.2). Patients were treated with an ACT manual administered by novice therapists and followed up for 6 months. They were randomized to immediate treatment (n = 33) or a 4-week waiting list (n = 10) with delayed treatment (n = 8). Treatment consisted of eight sessions, implemented twice weekly over 4 weeks. Primary outcomes were measured with the Panic and Agoraphobia Scale (PAS), the Clinical Global Impression (CGI), and the Mobility Inventory (MI). Results: At post-treatment, patients who received ACT reported significantly more improvements on the PAS and CGI (d = 0.72 and 0.89, respectively) than those who were on the waiting list, while improvement on the MI (d = 0.50) was nearly significant. Secondary outcomes were consistent with ACT theory. Follow-up assessments indicated a stable and continued improvement after treatment. The dropout rate was low (9%). Conclusions: Despite a clinically challenging sample and brief treatment administered by novice therapists, patients who received ACT reported significantly greater changes in functioning and symptomatology than those on the waiting list, with medium-to-large effect sizes that were maintained for at least 6 months. These proof-of-principle data suggest that ACT is a viable treatment option for treatment-resistant PD/A patients. Further work on switching to psychotherapy for nonresponders is clearly needed. © 2015 S. Karger AG, Basel

The role of mental disorders in the risk and speed of transition to alcohol use disorders among community youth

Background Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition. Method A total of 3021 community subjects (97.7% lifetime AU) aged 14-24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI. Results Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition. Conclusions Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AU

Do subthreshold psychotic experiences predict clinical outcomes in unselected non-help-seeking population-based samples? A systematic review and meta-analysis, enriched with new results

Background The base rate of transition from subthreshold psychotic experiences (the exposure) to clinical psychotic disorder (the outcome) in unselected, representative and non-help-seeking population-based samples is unknown. Method A systematic review and meta-analysis was conducted of representative, longitudinal population-based cohorts with baseline assessment of subthreshold psychotic experiences and follow-up assessment of psychotic and non-psychotic clinical outcomes. Results Six cohorts were identified with a 3-24-year follow-up of baseline subthreshold self-reported psychotic experiences. The yearly risk of conversion to a clinical psychotic outcome in exposed individuals (0.56%) was 3.5 times higher than for individuals without psychotic experiences (0.16%) and there was meta-analytic evidence of dose-response with severity/persistence of psychotic experiences. Individual studies also suggest a role for motivational impairment and social dysfunction. The evidence for conversion to non-psychotic outcome was weaker, although findings were similar in direction. Conclusions Subthreshold self-reported psychotic experiences in epidemiological non-help-seeking samples index psychometric risk for psychotic disorder, with strong modifier effects of severity/persistence. These data can serve as the population reference for selected and variable samples of help-seeking individuals at ultra-high risk, for whom much higher transition rates have been indicate

Evidence that bipolar disorder is the poor outcome fraction of a common developmental phenotype: an 8-year cohort study in young people

Background Reported rates of bipolar syndromes are highly variable between studies because of age differences, differences in diagnostic criteria, or restriction of sampling to clinical contacts. Method In 1395 adolescents aged 14-17 years, DSM-IV (hypo)manic episodes (manic and hypomanic episodes combined), use of mental health care, and five ordinal subcategories representing the underlying continuous score of (hypo)manic symptoms (‘mania symptom scale') were measured at baseline and approximately 1.5, 4 and 10 years later using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI). Results Incidence rates (IRs) of both (hypo)manic episodes and (hypo)manic symptoms (at least one DSM-IV core symptom) were far higher (714/105 person-years and 1720/105 person-years respectively) than traditional estimates. In addition, the risk of developing (hypo)manic episodes was very low after the age of 21 years [hazard ratio (HR) 0.031, 95% confidence interval (CI) 0.0050-0.19], independent of childhood disorders such as attention deficit hyperactivity disorder (ADHD). Most individuals with hypomanic and manic episodes were never in care (87% and 62% respectively) and not presenting co-morbid depressive episodes (69% and 60% respectively). The probability of mental health care increased linearly with the number of symptoms on the mania symptom scale. The incidence of the bipolar categories, in particular at the level of clinical morbidity, was strongly associated with previous childhood disorders and male sex. Conclusions This study showed, for the first time, that experiencing (hypo)manic symptoms is a common adolescent phenomenon that infrequently predicts mental health care use. The findings suggest that the onset of bipolar disorder can be elucidated by studying the pathway from non-pathological behavioural expression to dysfunction and need for car

Danger and loss events and the incidence of anxiety and depressive disorders: a prospective-longitudinal community study of adolescents and young adults

Background There are inconclusive findings regarding whether danger and loss events differentially predict the onset of anxiety and depression. Method A community sample of adolescents and young adults (n=2304, age 14-24 years at baseline) was prospectively followed up in up to four assessments over 10 years. Incident anxiety and depressive disorders were assessed at each wave using the DSM-IV/M-CIDI. Life events (including danger, loss and respectively mixed events) were assessed at baseline using the Munich Event List (MEL). Logistic regressions were used to reveal associations between event types at baseline and incident disorders at follow-up. Results Loss events merely predicted incident ‘pure' depression [odds ratio (OR) 2.4 per standard deviation, 95% confidence interval (CI) 1.5-3.9, p<0.001] whereas danger events predicted incident ‘pure' anxiety (OR 2.3, 95% CI 1.1-4.6, p=0.023) and ‘pure' depression (OR 2.5, 95% CI 1.7-3.5, p<0.001). Mixed events predicted incident ‘pure' anxiety (OR 2.9, 95% CI 1.5-5.7, p=0.002), ‘pure' depression (OR 2.4, 95% CI 1.6-3.4, p<0.001) and their co-morbidity (OR 3.6, 95% CI 1.8-7.0, p<0.001). Conclusions Our results provide further evidence for differential effects of danger, loss and respectively mixed events on incident anxiety, depression and their co-morbidity. Since most loss events referred to death/separation from significant others, particularly interpersonal loss appears to be highly specific in predicting depressio

converging evidence from an intermediate phenotype approach

Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain’s evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders