Subtle gene–environment interactions driving paranoia in daily life

Division of Psychological Medicine, Institute of Psychiatry, London, UK
Genes Brain and Behavior (Impact Factor: 3.66). 01/2009; 8(1):5 - 12. DOI: 10.1111/j.1601-183X.2008.00434.x
Source: PubMed


It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val158Met and BDNF Val66Met genotypes. Catechol-O-methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene–environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.

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Available from: Catherine Derom
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    • "Some genetic polymorphisms, such as in Dysbindin, have been shown to act as a moderating factor on both schizotypal personality traits and cognition [28]. Schizotypal personality traits may be related to BDNF genotype, given that healthy met carriers show more stress-induced paranoid thoughts than val homozygotes [29], and schizophrenia-like traits are more often observed in relatives of people with schizophrenia who may share genes associated with schizophrenia [30] [31] [32] [33]. "
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    ABSTRACT: The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed.
    Full-text · Article · Aug 2014 · Behavioural Brain Research
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    • "Some recent studies applied this methodology in examining the effect of genes on stress-sensitivity as a risk factor for MDD (Wichers et al., 2007a; Wichers et al., 2009a) and psychosis (Van Winkel et al., 2008; Simons et al., 2009; Collip et al., 2011). Only two ESM studies examined the moderating effect of the BDNF Val66Met polymorphism on stress sensitivity, operationalized as emotional responses to minor stressors in daily life (Simons et al., 2009; Wichers et al., 2008b). These studies reported that Met-carriers respond with more negative affect (NA) or paranoia to minor daily life stressors. "
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    ABSTRACT: A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factorVal66Met (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNFVal66Met genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in “Val/Met” carriers of BDNFVal66Met compared to “Val/Val” carriers. Positive emotions neutralized the moderating effect of BDNFVal66Met genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility.
    Full-text · Article · Jun 2014 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    • "In accordance with previous work [31], momentary paranoia was measured with the ESM item I feel suspicious. "
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    ABSTRACT: Paranoia embodies altered representation of the social environment, fuelling altered feelings of social acceptance leading to further mistrust. Mindfulness-based cognitive therapy (MBCT) may relieve paranoia and reduce its impact on social acceptance. To determine whether MBCT alters momentary feeling of paranoia and social acceptance in daily life. Randomized controlled trial of daily-life repeated measures (up to 120 per participant) before and after allocation to MBCT or waiting list control. Volunteer sample of 130 eligible men and women with residual affective dysregulation after at least one episode of major depressive disorder. Eight weeks of MBCT in groups of 10-15 participants in addition to participants' usual treatment. Daily-life ratings of paranoia and social acceptance. This manuscript concerns additional analyses of the original trial; hypotheses were developed after data collection (focus initially on depressive symptoms) but before data analysis. Sixty-six participants were assigned to the waiting list control group and 64 to the MBCT intervention group, of whom 66 and 61 respectively were included in the per-protocol analyses. Intention-to-treat analyses revealed a significant group by time interaction in the model of momentary paranoia (b = -.18, p<0.001, d = -0.35) and social acceptance (b = .26, p<0.001, d = 0.41). Paranoia levels in the intervention group were significantly reduced (b = -.11, p<0.001) and feelings of social acceptance significantly increased (b = .18, p<0.001), whereas in the Control condition a significant increase in paranoia (b = .07, p = 0.008) and a decrease in social acceptance was apparent (b = -.09, p = 0.013). The detrimental effect of paranoia on social acceptance was significantly reduced in the MBCT, but not the control group (group by time interaction: b = .12, p = 0.022). MBCT confers a substantial benefit on subclinical paranoia and may interrupt the social processes that maintain and foster paranoia in individuals with residual affective dysregulation. Netherlands Trial Register NTR1084.
    Full-text · Article · Jun 2013 · PLoS ONE
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