Psychosis‐inducing effects of cannabis are related to both childhood abuse and COMT genotypes

Abstract

Objective To test whether the association between childhood abuse, cannabis use and psychotic experiences (PEs) was moderated by the COMT (catechol‐O‐methyltransferase) gene. Method Psychotic experiences (PEs), childhood abuse, cannabis use and COMT Val158Met genotypes were assessed in 533 individuals from the general population. Data were analysed hierarchically by means of multiple linear regression models. Results Childhood abuse showed a significant main effect on both positive (β = 0.09; SE = 0.04; P = 0.047) and negative PEs (β = 0.11; SE = 0.05; P = 0.038). A significant three‐way interaction effect was found among childhood abuse, cannabis use and the COMT gene on positive PEs (β = −0.30; SE = 0.11; P = 0.006). This result suggests that COMT genotypes and cannabis use only influenced PE scores among individuals exposed to childhood abuse. Furthermore, exposure to childhood abuse and cannabis use increased PE scores in Val carriers. However, in individuals exposed to childhood abuse but who did not use cannabis, PEs increased as a function of the Met allele copies of the COMT gene. Conclusion Cannabis use after exposure to childhood abuse may have opposite effects on the risk of PEs, depending on the COMT genotypes providing evidence for a qualitative interaction. Val carriers exposed to childhood abuse are vulnerable to the psychosis‐inducing effects of cannabis.

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).…”

Psychotic Experiences in the Adaptation Process to a New Social Environment

“…Yaygınlık için yanıtlar 0 (hiçbir zaman, bazen) ve 1 (sıklıkla, neredeyse sürekli) olarak yeniden kodlanmaktadır (Stefanis ve ark. 2002, Alemany ve ark. 2014).…”

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

“…Another population registry-based study found that family history of schizophrenia increased both the risk of schizophrenia and of acute cannabis-induced psychosis [25]. A history of child abuse (including sexual, physical, and/or emotional abuse) or neglect also increases the risk of developing schizophrenia after cannabis use [26][27][28][29][30][31]. Two large, population-based, longitudinal studies, in Greece and the Netherlands, both replicated findings that childhood maltreatment and cannabis use precede and are independently associated with increased risk of later psychosis, and that the combination of the 2 risk factors is synergistically associated with an increased risk of psychosis [28].…”

“…Two studies found a 3-way interaction between the COMT SNP, cannabis use, and a history of child abuse. Carriers of the COMT Val/Val genotype who were exposed to both childhood abuse and cannabis had more severe psychotic symptoms, whereas amongst carriers of a Met allele, childhood abuse was associated with more severe psychotic symptoms in noncannabis users [26,27]. AKT1 encodes for a protein kinase involved in second messenger transduction at the CB 1 R, and has also been implicated in increasing the risk for psychosis in cannabis users.…”