<i>COMT</i> Val158Met and <i>MTHFR</i> C677T moderate risk of schizophrenia in response to childhood adversity

Debost, Jean Christophe P.G.; Debost, M.; Grove, Jakob; Mors, Ole; Hougaard, David M.; Børglum, Anders D.; Mortensen, Preben Bo; Petersen, Liselotte

doi:10.1111/acps.12761

Cited by 12 publications

(13 citation statements)

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“…Most of the studies, including robust prospective (Lataster, Myin-Germeys, Lieb, Wittchen, & van Os, 2012; Mansueto et al, 2019; Ouellet-Morin et al, 2015) and semi-prospective studies (Janssen et al, 2005; Konings et al, 2012; van Nierop et al, 2014), retrospectively assessed CA with self-report measures, and only a few robust studies used register-based information (Debost et al, 2017; Paksarian et al, 2015; Räikkönen et al, 2011; Walker et al, 1981; Wicks et al, 2010), thus preventing inferences about causality from being drawn. A recent meta-analysis found that prospective and retrospective measures of CA may identify different risk pathways to mental illness (Baldwin, Reuben, Newbury, & Danese, 2019).…”

Section: Resultsmentioning

confidence: 99%

“…Another main caveat is the quality and heterogeneity of the measurement instruments utilized. Only 11.6% (n = 14) of the studies assessed CA using documented evidence (Debost et al, 2017;Paksarian, Eaton, Mortensen, Merikangas, & Pedersen, 2015;Räikkönen et al, 2011;Walker, Cudeck, Mednick, & Schulsinger, 1981;Wicks, Hjern, & Dalman, 2010) or semi-structured interviews (such as the Childhood Experience of Care and Abuse (CECA) interview; Bifulco, Brown, and Harris, 1994), while the majority relied on self-report instruments (most frequently the Childhood Trauma Questionnaire (CTQ): Bernstein et al, 1994Bernstein et al, , 2003. The latter instruments may be more susceptible to recall bias in clinical populations, although some studies have suggested they are not (Schäfer et al, 2011).…”

Section: Methodological Appraisalmentioning

confidence: 99%

“…COMT Val 158 Met × CA interaction has been associated with psychotic experiences in a non-FEP prospective study (Vinkers et al, 2013). However, such G × E was not replicated by other studies (Debost et al, 2017;Ramsay et al, 2013;Trotta et al, 2019), and no relationship was found with FKBP5 (Ajnakina et al, 2014), BDNF (Ramsay et al, 2013), MTHFR C677T (Debost et al, 2017), DRD2 or AKT1 risk haplotypes (Trotta et al, 2019). Only one study used genome-wide association and polygenic risk score methods in FEP, with negative findings (Trotta et al, 2016).…”

Section: (Continued )mentioning

confidence: 96%

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Childhood adversity and psychosis: a systematic review of bio-psycho-social mediators and moderators

et al. 2020

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Abstract The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.

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Section: Resultsmentioning

confidence: 99%

Section: Methodological Appraisalmentioning

confidence: 99%

Section: (Continued )mentioning

confidence: 96%

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Childhood adversity and psychosis: a systematic review of bio-psycho-social mediators and moderators

et al. 2020

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“…Collip et al followed up on the Winkel et al study with a larger sample and confirmed a significant interaction between COMT Met allele carriers, stress, and psychosis [ 95 ]. Interestingly, a study by Stefanis et al investigated the interaction between COMT Val158Met and psychosis in a sample of young men entering compulsory military training, and found that exposure to stress at army induction was associated with psychotic symptoms and that carriers of the COMT Val allele were more susceptible to the effect of stress, contradicting data from the previous studies [ 96 , 97 ]. COMT has also been investigated as a moderator between childhood adversity and psychosis [ 98 ].…”

Section: Gene-environment (Gxe) Interactionsmentioning

confidence: 92%

Gene-Environment Interactions in Schizophrenia: A Literature Review

Wahbeh

Avramopoulos

2021

Genes

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Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant status also play a role. Whenever genetic and non-genetic factors co-exist, interaction between the two is likely. This means that certain exposures would only be of consequence given a specific genetic makeup. Here, we provide a brief review of studies reporting evidence of such interactions, exploring genes and variants that moderate the effect of the environment to increase risk of developing psychosis. Discovering these interactions is crucial to our understanding of the pathogenesis of complex disorders. It can help in identifying individuals at high risk, in developing individualized treatments and prevention plans, and can influence clinical management.

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“…Dysregulation of dopamine has long been considered a crucial part of the pathophysiology of schizophrenia and a great deal of research has been done to investigate the link between COMT polymorphisms and schizophrenia, particularly with respect to negative symptoms and cognition [69,70]. These studies have shown a variety of interesting results including some studies demonstrating significant interactions between cannabis use and COMT genotype and development of schizophrenia [17,71,72,73,74,75,76,77]. In 2005 Caspi et al reported data on 803 individuals born in Dunedin, New Zealand (known as the Dunedin cohort) [76].…”

Section: Schizophreniamentioning

confidence: 99%

Cannabis and Psychosis Through the Lens of DSM-5

Pearson

Berry

2019

IJERPH

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Evidence for an association between cannabis and psychosis has been documented in literature in many forms including experimental studies, epidemiological data, and case series. The association has implications for psychotic outcomes ranging from mild to severe and occurring over minutes to years. Due to the huge variety of exposures and outcome measures reported, creating a coherent account of all the available information is difficult. A useful way to conceptualize these wide-ranging results is to consider the association between cannabis and psychosis as it occurs within the context of widely used DSM-5 diagnoses. In the present review we examine cannabis/psychosis associations as they pertain to Cannabis Intoxication, Cannabis-Induced Psychotic Disorder, and Schizophrenia. This allows for an understanding of the cannabis and psychosis association along something approaching a continuum. Cannabis intoxication becomes Cannabis-Induced Psychotic Disorder once certain severity and duration criteria are met and Cannabis-Induced Psychotic Disorder is heavily associated with future schizophrenia diagnoses.

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COMT Val158Met and MTHFR C677T moderate risk of schizophrenia in response to childhood adversity

Abstract: MTHFR C677T and COMT Val158Met interact with CA to increase risk of schizophrenia.

Cited by 12 publications

References 50 publications

Childhood adversity and psychosis: a systematic review of bio-psycho-social mediators and moderators

Childhood adversity and psychosis: a systematic review of bio-psycho-social mediators and moderators

Gene-Environment Interactions in Schizophrenia: A Literature Review

Cannabis and Psychosis Through the Lens of DSM-5

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