Positive symptoms in first-episode psychosis patients experiencing low maternal care and stressful life events: a pilot study to explore the role of the COMT gene

Abstract

COMT Val(158)Met moderates the effect of stress on psychotic symptoms. Exposure to stress is also associated with mesolimbic dopamine release in individuals experiencing low maternal care. We therefore test the hypothesis that recent stressful life events are associated with more severe positive symptoms (associated with mesolimbic dopamine release) in first-episode psychosis (FEP) patients who experienced low maternal care during childhood. We hypothesized that COMT Val(158)Met moderates this association. A total of 149 FEP patients recruited within the Psychosis Incident Cohort Outcome Study (PICOS) participated in the present study. Maternal care was assessed by the Parental Bonding Instrument (PBI), stressful life events were collected by the List of Events Scale and positive symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). We found that low maternal care and recent stressful life events were associated with higher level of positive symptoms at the onset (analysis of variance [ANOVA], p = 0.012), and that patients who were also homozygotes for the COMT Val(158) allele had the highest level of positive symptoms (ANOVA, p = 0.024). Low maternal care and severe stressful life events may contribute to a symptomatology characterized by more severe positive symptoms at the onset, possibly due to an increased mesolimbic dopamine release. Homozygosity for the COMT Val(158) allele seems to confer a biological predisposition to the stress-related hyperactivity of the mesolimbic dopaminergic system. The data imply that the mesolimbic dopaminergic system is involved in the mediation/modulation of the effect of stressful events on the vulnerability for psychosis.

Stressful life events and catechol-O-methyl-transferase (COMT ) gene in bipolar disorder

“…However, these results should be considered preliminary because they just reached conventional levels of significance and were not corrected for testing of the three genetic models. Clearly the results of this study warrant replication, but future research should also explore G × Es focusing on different types of stressors such childhood adversity (e.g., childhood abuse and neglect) as well as multiple interactions between genes and environments (e.g., gene-gene-environment interactions and (Ira et al, 2014) found that individuals exposed to low maternal care as a child (childhood adversity) and who experienced stressful life events in adulthood (proximal stress) reported more psychotic symptoms, and this relationship was strongest among the Val/Val COMT group. Similar work is needed in the field of bipolar disorder to build a more comprehensive etiological model that better reflects the complex dynamic between the environment and genetic factors.…”

“…gene-gene-environment interactions and environment-environmentgene interactions). For example, one study (Ira et al, 2014) found that individuals exposed to low maternal care as a child (childhood adversity) and who experienced stressful life events in adulthood (proximal stress) reported more psychotic symptoms, and this relationship was strongest amongst the Val/Val COMT group. Similar work is needed in the field of bipolar disorder to build a more comprehensive aetiological model that better reflects the complex dynamic between the environment and genetic factors.…”

Investigation of the COMT Val158Met variant association with age of onset of psychosis, adjusting for cannabis use

“…COMT remains an interesting candidate gene for gene‐environment interactions in psychosis since it modulates dopamine function, is dynamically regulated and its expression alters with environmental stimuli (Tunbridge, 2010). In psychosis, the Val/Val rs4680 genotype may predispose individuals to stress‐related mesolimbic hyperactivity (Ira et al., 2014) and is known to increase the vulnerability to psychosis after cannabis use in those exposed to childhood abuse (Alemany et al., 2014). rs4680 has also been reported to moderate the effect of stress in induction of psychotic symptoms in a study of army recruits (Stefanis et al., 2007).…”

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events

“…41 On the basis of our previous work, 42 only ‘severe stressful life events' (that is, death of a family member, sexual or physical abuse, being accused of having committed a crime, sentence of imprisonment, being exposed to war and natural catastrophes, family breakdown, being removed from home, sentimental breakdown and severe physical illness) were taken into account.…”