Traumatic experiences in childhood and adolescence: a meta-analysis of prospective studies assessing risk for psychosis.

Evidence of the association between traumatic experiences and psychosis are uncertain with respect to temporal order, clinical outcomes and the role of the age and genetic liability. The aim of the present meta-analysis was to explore the temporal relationship between the development of psychosis and traumatic exposure using prospective studies and to examine the role of moderation factors on overall effect sizes. Studies were identified by searching Embase-Ovid, PsycINFO (EBSCO), Pubmed, Scopus, Web of Science databases, and yielded an initial total of 9016 papers, leaving finally 23 after the screening process. Three sets of meta-analyses estimated the risk of developing psychotic experiences or full clinical psychosis by having experienced maltreatment by an adult or bullying by peers or parental death, using the random-effects model. Bullying by peers (OR = 2.28 [1.64, 4.34]), maltreatment by an adult (OR = 2.20 [1.72, 2.81]) and parental death (OR = 1.24 [1.06, 1.44]) all increased the risk of psychosis. Moderator analysis showed that negative effects of bullying were detected especially in those with genetic liability for psychosis and exposure to multiple trauma types; studies with higher prevalence of males showed a stronger risk for those exposed to parental death. No significant meta-regression was found between the risk of developing a full clinical psychosis or a psychotic experience. Lack of studies hampered the results about the age of trauma occurrence. The cumulative effect of being bullied from peers and experiencing other adversities during childhood and/or adolescence, together with genetic liability for psychosis, appears to confer the highest risk for developing psychotic symptoms later in life.

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.

BACKGROUND: Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. METHODS: A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. RESULTS: We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. CONCLUSIONS: The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.