ObjectiveThe interaction of single nucleotide polymorphisms with both distal and proximal environmental factors across the extended psychosis phenotype is understudied. This study examined (i) the interaction of relevant SNPs with both early‐life adversity and proximal (momentary) stress on psychotic experiences (PEs) in an extended psychosis sample; and (ii) differences between early‐psychosis and non‐clinical groups for these interactions.MethodsTwo hundred and forty‐two non‐clinical and 96 early‐psychosis participants were prompted randomly eight times daily for 1 week to complete assessments of current experiences, including PEs and stress. Participants also reported on childhood trauma and were genotyped for 10 SNPs on COMT, RGS4, BDNF, FKBP5, and OXTR genes.ResultsUnlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early‐psychosis than in the non‐clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early‐psychosis group. No interactions emerged with COMT or BDNF variants.ConclusionIndividual differences in relevant stress‐regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily‐life manifestation of PEs across the psychosis continuum.
AimThe present study employed Experience Sampling Methodology to examine whether the interaction between childhood bullying and FKBP5 variability (i) is associated with the expression of psychotic-like experiences, paranoia, and negative affect, and (ii) moderates psychotic-like, paranoid, and affective reactivity to different forms of momentary stress (situational and social) in daily life.MethodsA total of 206 nonclinical young adults were interviewed for bullying with the Childhood Experience of Care and Abuse and were prompted randomly eight times daily for one week to complete assessments of their current experiences, affect, and stress appraisals. Participants were genotyped for three FKBP5 single nucleotide polymorphisms (SNPs) (rs3800373, rs9296158, and rs1360780) that have been linked to hypothalamus-pituitary-adrenal axis reactivity. Multilevel analyses were conducted to examine the effect of the interaction between childhood bullying and the FKBP5 haplotype derived from these three SNPs.ResultsThe interaction between bullying and the FKBP5 haplotype was associated with positive, but not negative, psychotic-like experiences, paranoia, and negative affect. The bullying x FKBP5 interaction also moderated the association of a social stress appraisal (specifically, being alone because people do not want to be with you) with psychotic-like experiences and negative affect in daily life. Simple slopes analyses indicated that, in all cases, the associations were significantly increased by exposure to bullying in participants with the risk haplotype, but not for those with the non-risk haplotype.DiscussionThe present study provides the first evidence of the interplay between childhood bullying and FKBP5 variability in the real-world expression of psychosis proneness and social stress reactivity. The findings underscore the importance of investigating how gene-environment interactions are involved in mechanistic pathways to the extended psychosis phenotype and lend further support to the increasing relevance given to socially defeating appraisals in the experience of reality distortion.
Childhood trauma exposure is a robust environmental risk factor for psychosis. However, not all exposed individuals develop psychotic symptoms later in life. The Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been suggested to moderate the psychosis-inducing effects of childhood trauma in clinical and nonclinical samples. Our study aimed to explore the interaction effect between childhood trauma and the BDNF Val66Met polymorphism on subclinical psychotic experiences (PEs). This was explored in two nonclinical independent samples: an undergraduate and technical-training school student sample (n=808, sample 1) and a female twin sample (n=621, sample 2). Results showed that childhood trauma was strongly associated with positive and negative PEs in nonclinical individuals. A BDNF Val66Met x childhood trauma effect on positive PEs was observed in both samples. These results were discordant in terms of risk allele: while in sample 1 Val allele carriers, especially males, were more vulnerable to the effects of childhood trauma regarding PEs, in sample 2 Met carriers presented higher PEs scores when exposed to childhood trauma, compared with Val carriers. Moreover, in sample 2, a significant interaction was also found in relation to negative PEs. Our study partially replicates previous findings and suggests that some individuals are more prone to develop PEs following childhood trauma because of a complex combination of multiple factors. Further studies including genetic, environmental and epigenetic factors may provide insights in this field.
BackgroundGene-environment interaction (GxE) research has highlighted the importance of investigating the FK506 binding protein 51 (FKBP5) gene as a sensitivity gene. However, previous GxE studies with FKBP5 have not measured the full environmental spectrum or applied statistical tests to discern whether the GxE interaction fits better with the differential-susceptibility or diathesis-stress hypotheses. This study examined whether single nucleotide polymorphisms (SNPs) on FKBP5 gene moderate the association of positive and negative recent life events (LEs) with depressive symptoms, state-anxiety, neuroticism, and social anxiety traits.MethodsA total of 86 nonclinical young adults were administered psychological measures and were genotyped for five FKBP5 SNPs (rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916).ResultsRegression analyses indicated significant GxE interactions for social anxiety and neuroticism. The interactions predicting neuroticism fit different models for different SNPs, although the overall effect indicated by the haplotype was consistent with the differential-susceptibility hypothesis: the risk-haplotype group presented higher neuroticism in the presence of more negative LEs and lower neuroticism in the presence of more positive LEs. The GxE interactions for social anxiety were consistent with the diathesis-stress model. The lack of significance in the for-better side for social anxiety might be related to the fact that it mapped onto low extraversion, which is associated with a lower permeability to positive experiences.DiscussionFindings underscore the importance of testing the differential-susceptibility model in relation to FKBP5 to adequately characterize its role in healthy and pathological developmental processes.
Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
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