Catechol-o-Methyltransferase Genotype and Childhood Trauma May Interact to Impact Schizotypal Personality Traits

Abstract

We attempt to identify gene by childhood abuse interactions which predispose to the development of schizotypal traits in a familial bipolar disorder (BD) sample. Self-report measures of schizotypal personality traits (Schizotypal Personality Scale) and childhood maltreatment (Childhood Trauma Questionnaire) were administered to 222 participants from 44 families with BD. Variants of catechol-o-methyltransferase (COMT) and four other dopamine pathway-related genes: DRD4, DRD2,MAOA, and SLC6A3, were typed. BD type I (BD I) subjects scored significantly higher than their unaffected relatives on the Schizotypal Personality Scale. The val allele of the Val158 Met polymorphism of the COMT gene was associated with increased schizotypal personality trait scores in individuals exposed to higher levels of self-reported childhood trauma (p < 0.05). There was no direct effect of the val158met polymorphism on schizotypal personality traits. Further, no passive correlation between COMT genotype and childhood trauma was found. We raise the possibility that genetically-driven variation in COMT may interact with childhood trauma to contribute to the risk of developing schizotypal personality traits.

Relationship between the COMT-Val158Met and BDNF-Val66Met Polymorphisms, Childhood Trauma and Psychotic Experiences in an Adolescent General Population Sample

“…This adds to the existing literature suggesting increased paranoia [70], schizotypal traits [41] and psychotic experiences [39,40] among Val-Val individuals in the context of stress or trauma. Specifically, young people with childhood traumatic experiences who had the COMT Val-Val genotype were more likely to experience psychotic experiences compared with ValMet and Met-Met individuals.…”

“…Our results suggesting a possible interaction between the COMT-Val158Met Val-Val genotype and childhood trauma in association with psychotic experiences are consistent with previous findings regarding gene-environment interactions between COMT-Val158Met and stressful/traumatic experiences in association with the extended psychosis phenotype. Consistent with our findings, the Val allele was associated with self-reported psychotic symptoms interacting with cannabis use in an adult Dutch population sample [39] and with transient self-reported psychotic experiences during the stress of army induction in a sample (aged 18-24 years) of Greek male conscripts [40] and Val-Val genotype has been associated with more enduring schizotypal traits in those with the Val-Val genotype (but not other genotypes) in the context of self-reported childhood trauma in an adult sample [41]. It is interesting that we have found similar associations in adolescents, despite the changing clinical significance of psychotic experiences with increasing age [10].…”

“…Furthermore, the COMT-Val158Met Val allele has been associated with self-reported psychotic experiences in the context of stress and cannabis use in a Dutch adult population sample [39]and with the stress of army induction in a Greek male conscript sample [40]. COMTVal158Met has also been associated with increased schizotypal personality trait scores in Val-Val individuals exposed to higher levels of self-reported childhood trauma [41]. BDNF, on the other hand, has an established role in neuronal development and cell survival in response to stress [42] and is abnormally expressed in schizophrenia [43].…”

Psychiatric genetics in South Africa: cutting a rough diamond

“…This indicates that another polymorphism in this gene, or another gene in the region, could account for linkage to the chromosome 22q region. In other studies of this South African bipolar disorder cohort, the Val158Met polymorphism of COMT was found to: (i) influence dissociation when previous childhood abuse was taken into account 78 ; (ii) indirectly impact schizotypal personality traits as a result of childhood trauma 80 and (iii) possibly be implicated in right handedness and by proxy, brain lateralisation 76 , although this final finding is debatable.…”

“…73 Research into the genetic component of bipolar disorder in South African populations has been predominantly performed by Savitz and colleagues, using a cohort of Caucasian families, mostly of Afrikaner and British descent (approximately 47 pedigrees of 350 samples). [74][75][76][77][78][79][80] Many of these studies have focussed on gene-environment interactions with potential endophenotypes or intermediate traits. As mentioned previously, the use of endophenotypes in this manner reduces reliance on heterogeneous DSM diagnoses and therefore potentially simplifies the identification of genetic susceptibility factors.…”