Violent aggression predicted by multiple pre-adult environmental hits.

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

Neuroticism, rumination, depression and suicidal ideation: A moderated serial mediation model across four countries.

Background/objective: Research has highlighted the role of neuroticism, rumination, and depression in predicting suicidal thoughts, but studies on how these variables interplay are scarce. The aims of the present study were to test a model in which emotional stability (i.e., low neuroticism) would act as an antecedent and moderator of rumination and depressed mood in the prediction of suicidal ideation (i.e., moderated serial-mediation), and to explore their replicability across four countries and sex, among college students as an at-risk-group for suicide. Method: Participants were 3482 undergraduates from U.S, Spain, Argentina, and the Netherlands. Path analysis and multi-group analysis were conducted. Results: Emotional stability was indirectly linked to suicidal ideation via rumination and depressed mood. Moreover, emotional stability moderated the associations between rumination and depressed mood, and between depressed mood and suicidal ideation. Findings were consistent in males and females, and across countries studied. Discussion: Regardless of sex and country, people with low emotional stability reported higher levels of rumination, which in turn was associated with more depressed mood, and these were associated with higher reports of suicidal thoughts. This cascade of psychological risk factors for suicidal ideation seems to be more harmful in people who endorse low levels of emotional stability.

The interaction between the ZNF804A gene and cannabis use on the risk of psychosis in a non-clinical sample.

The ZNF804A gene and cannabis use are risk factors for psychosis and both have also been associated with schizotypal traits. This study aimed to investigate: i) the association of lifetime cannabis use (and its dose effect) with schizotypal personality traits, and ii) whether the genetic variability at ZNF804A gene modulates that association. Our sample consisted of 385 Spanish non-clinical subjects (43.1% males, mean age = 21.11(2.19)). Schizotypy was evaluated using the three factors of the Schizotypal Personality Questionnaire-Brief (SPQ-B): Cognitive-Perceptual (SPQ-CP), Interpersonal (SPQ-I) and Disorganized (SPQ-D). Subjects were classified according to their frequency of cannabis consumption, and dichotomized as users or non-users. The effects of a genetic variant of ZNF804A (rs1344706) and cannabis use, as well as their interaction, on each of the three SPQ-B factors were assessed using linear models and permutation tests. Sex, SCL anxiety scores and use of other drugs were included as covariates. Our analysis showed a significant relationship between ZNF804A and SPQ-I: AA genotype was associated with higher scores (ß = 0.885 pFDR = .018). An interaction between the AA genotype and lifetime cannabis use was found in SPQ-CP (ß = 1.297 pFDR = 0.018). This interaction showed a dose-effect pattern among AA subjects: schizotypy scores increased with increasing frequency of cannabis use (sporadic users: ß = 0.746 pFDR = 0.208; monthly users: ß = 1.688 pFDR = 0.091; intense users: ß = 1.623 pFDR = 0.038). These results add evidence on that the ZNF804A gene is associated with schizotypy and suggest that the interaction between cannabis use and ZNF804A genotype could modulate psychosis proneness.

Season of birth and subclinical psychosis: systematic review and meta-analysis of new and existing data.

Season of birth (SOB) has been shown to modify the risk of several health outcomes, including a number of neuropsychiatric disorders. Empirical evidence indicates that subclinical forms of psychosis in the general population share some risk factors with categorical diagnoses of psychosis. Hence, by systematically reviewing and meta-analyzing new and existing data, the current work aimed to determine whether there is evidence of an association between winter SOB and subclinical psychosis in the general population. Our meta-analytic results do not indicate an association between winter SOB and schizotypy in adult populations, although they indicate winter SOB may be a risk factor for psychotic experiences or symptoms in children around 12-15 years (OR=1.12, 95%CI:1.03-1.21). In the whole new dataset for adults (n=481, mean age=22.8 years) no association was detected in either an unadjusted model or adjusting for gender and age. Overall, our results indicate that the association between winter SOB and increased subclinical psychosis may hold in children, but does not in the broad general adult population. Nevertheless, the epidemiological and clinicopathological significance of winter SOB as a risk factor for subclinical psychosis would probably be slight due to the small effect sizes indicated by the reports available to date.

Spanish adaptation of the Expectancy Questionnaire (EQ) about alcohol effects in adolescents.

BACKGROUND: Alcohol-related expectancies are especially relevant in relation to alcohol consumption during adolescence. The main aim of this study was to adapt and translate into Spanish (Castilian) the Expectancy Questionnaire (EQ), and to study its psychometric properties in adolescents. METHOD: The sample was composed of 514 adolescents (57.20% female, mean age = 15.21; SD = .63) who completed the EQ and the alcohol consumption questionnaire AIS-UJI. RESULTS: Confirmatory factor analysis indicated that an eight-factor model, grouped into two general factors of positive and negative expectancies, had acceptable fit indices. Cronbach's alphas ranged from .75 to .96. Finally, the structural equation model showed that positive expectancies were positively related to alcohol use, whereas negative expectancies were negatively related to drinking. CONCLUSIONS: Results showed that the Spanish version of the EQ for adolescents is a valid and reliable questionnaire to measure expectancies about alcohol effects.

Cognition and the five-factor model of the positive and negative syndrome scale in schizophrenia.

Different exploratory and confirmatory factorial analyses of the Positive and Negative Syndrome Scale (PANSS) have found a number of factors other than the original positive, negative, and general psychopathology. Based on a review of previous studies and using confirmatory factor analyses (CFA), Wallwork et al. (Schizophr Res 2012; 137: 246-250) have recently proposed a consensus five-factor structure of the PANSS. This solution includes a cognitive factor which could be a useful measure of cognition in schizophrenia. Our objectives were 1) to study the psychometric properties (factorial structure and reliability) of this consensus five-factor model of the PANSS, and 2) to study the relationship between executive performance assessed using the Wisconsin Card Sorting Test (WCST) and the proposed PANSS consensus cognitive factor (composed by items P2-N5-G11). This cross-sectional study included a final sample of 201 Spanish outpatients diagnosed with schizophrenia. For our first objective, CFA was performed and Cronbach's alphas of the five factors were calculated; for the second objective, sequential linear regression analyses were used. The results of the CFA showed acceptable fit indices (NNFI=0.94, CFI=0.95, RMSEA=0.08). Cronbach's alphas of the five factors were adequate. Regression analyses showed that this five-factor model of the PANSS explained more of the WCST variance than the classical three-factor model. Moreover, higher cognitive factor scores were associated with worse WCST performance. These results supporting its factorial structure and reliability provide robustness to this consensus PANSS five-factor model, and indicate some usefulness of the cognitive factor in the clinical assessment of schizophrenic patients.