Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults.

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.

Liprin alfa 2 gene expression is increased by cannabis use and associated with neuropsychological function.

The relation of heavy cannabis use with decreased neuropsychological function has frequently been described but the underlying biological mechanisms are still largely unknown. This study investigates the relation of cannabis use with genome wide gene expression and subsequently examines the relations with neuropsychological function. Genome-wide gene expression in whole blood was compared between heavy cannabis users (N = 90) and cannabis naïve participants (N = 100) that were matched for psychotic like experiences. The results were validated using quantitative real-time PCR. Psychotic like experiences were assessed using the Comprehensive Assessment of Psychotic Experiences (CAPE). Neuropsychological function was estimated using four subtasks of the Wechsler Adult Intelligence Scale (WAIS). Subsequent in vitro studies in monocytes and a neuroblastoma cell line investigated expression changes in response to two major psychotropic components of cannabis; tetrahydrocannabinol (THC) and cannabidiol (CBD). mRNA expression of Protein Tyrosine Phosphatase Receptor Type F Polypeptide-Interacting-Protein Alpha-2 (PPFIA2) was significantly higher in cannabis users (LogFold Change 0.17) and confirmed by qPCR analysis. PPFIA2 expression level was negatively correlated with estimated intelligence (B=-22.9, p = 0.002) also in the 100 non-users (B=-28.5, p = 0.037). In vitro exposure of monocytes to CBD led to significant increase in PPFIA2 expression. However, exposure of monocytes to THC and neuroblastoma cells to THC or CBD did not change PPFIA2 expression. Change in PPFIA2 gene expression in response to cannabinoids is a putative mechanism by which cannabis could influence neuropsychological functions. The findings warrant further exploration of the role of PPFIA2 in cannabis induced changes of neuropsychological function, particularly in relation to CBD.

Advanced paternal age and vulnerability to psychotic-like experiences in the offspring.

OBJECTIVE: To investigate whether advanced paternal age is associated with increased psychotic-like experiences (PLEs) and increased sensitivity to Cannabis in the offspring. METHODS: A cross-sectional population-based study in 1684 participants aged 18 to 25. RESULTS: We found no association of paternal age with PLEs. Only the positive dimension subscale was associated to paternal age, but that could be largely contributed to outliers. Also no increased sensitivity to Cannabis smoking was apparent. CONCLUSION: In the general population, we did not find robust support for an association between paternal age and vulnerability to PLEs in 18-25year old offspring.

Cannabis use and subclinical positive psychotic experiences in early adolescence: findings from a Dutch survey.

AIMS: To investigate the association between early cannabis use and subclinical psychotic experiences, distinguishing between five levels of use: never used, discontinued use (life-time users who did not use in the preceding year), experimental use, regular use and heavy use. DESIGN: Cross-sectional observational study. SETTING: Dutch Health Behaviour in School-aged Children (HBSC) study, 2005 wave. PARTICIPANTS: A total of 4552 secondary school children aged 12-16 years. MEASUREMENTS: Cannabis use, Community Assessment of Psychic Experiences (CAPE) positive scale, confounding factors: age, gender, family affluence, household composition, social support, alcohol use, cigarette smoking, ethnicity and urbanicity. FINDINGS: The association between cannabis use and subclinical positive symptoms was confirmed, and remained significant after extensive adjustment for potential confounders. Associations were found for all user groups, with strongest associations for the discontinued use group (ß = 0.061, P = 0.000) and for the heavy use group (ß = 0.065, P = 0.000). CONCLUSIONS: There is an enduring association between cannabis use at an early age and subclinical positive psychotic experiences, even after abstaining from cannabis for at least 1 year.

Screening capacity of the Multidimensional Anxiety Scale for Children (MASC) for DSM-IV anxiety disorders.

BACKGROUND: The Multidimensional Anxiety Scale for Children (MASC) is a widely used self-report questionnaire for the assessment of anxiety symptoms in children and adolescents. METHODS: This study used receiver operating characteristic analyses to investigate the predictive value of the MASC total and scale scores for DSM-IV anxiety diagnoses in a referred sample. Eight- to 18-year-olds (n=212) were assessed with the MASC and Anxiety Disorders Interview Schedule for Children (ADIS-C). RESULTS: The MASC total score did not exceed the threshold for being judged as fair in predicting any ADIS-C/DSM-IV anxiety diagnosis. The Separation Anxiety scale and the Physical Symptoms scale predicted Panic Disorder (PAD) and Agoraphobia fairly accurately. The Social Anxiety scale predicted Social Phobia, and the Separation Anxiety scale predicted PAD to a moderate degree. The MASC scale Harm Avoidance did not predict any ADIS-C/DSM-IV diagnosis. CONCLUSIONS: These results suggest that the MASC may not be a valid screening instrument for DSM-IV diagnoses.