TY - JOUR
T1 - The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis
T2 - A transdiagnostic meta - analysis
AU - Vaessen, Thomas Stephanus Johannes
AU - de Jong, Lea
AU - Schafer, Annika Theresia
AU - Damen, Thomas
AU - Uittenboogaard, Aniek
AU - Krolinski, Pauline
AU - Nwosu, Chinyere Vicky
AU - Pinckaers, Florentina Maria Egidius
AU - Rotee, Iris Leah Marije
AU - Smeets, Antonius Petrus Wilhelmus
AU - Ermis, Aysegui
AU - Kennedy, James L.
AU - Nieman, Dorien H.
AU - Tiwari, Arun
AU - van Os, Jim
AU - Drukker, Marjan
PY - 2018/2/14
Y1 - 2018/2/14
N2 - Background Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. Objective A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). Data sources PubMed, Embase, PsychInfo. Study eligibility criteria All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. Study appraisal and synthesis methods A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". Results For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05 +/- 2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16 +/- 0.08). Limitation A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. Conclusion The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.
AB - Background Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. Objective A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). Data sources PubMed, Embase, PsychInfo. Study eligibility criteria All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. Study appraisal and synthesis methods A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". Results For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05 +/- 2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16 +/- 0.08). Limitation A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. Conclusion The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.
KW - O-METHYLTRANSFERASE GENE
KW - ULTRA-HIGH-RISK
KW - ENVIRONMENT INTERACTION
KW - SUBSTANCE USE
KW - SCHIZOPHRENIA
KW - METAANALYSIS
KW - EXPERIENCES
KW - SYMPTOMS
KW - GENOTYPE
KW - ONSET
U2 - 10.1371/journal.pone.0192658
DO - 10.1371/journal.pone.0192658
M3 - Article
C2 - 29444152
SN - 1932-6203
VL - 13
JO - PLOS ONE
JF - PLOS ONE
IS - 2
M1 - e0192658
ER -