Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder. A Systematic Review

TY - JOUR

T1 - Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder. A Systematic Review

AU - Misiak, Błażej

AU - Stramecki, Filip

AU - Gawęda, Łukasz

AU - Prochwicz, Katarzyna

AU - Sąsiadek, Maria M

AU - Moustafa, Ahmed A

AU - Frydecka, Dorota

PY - 2018/6

Y1 - 2018/6

N2 - Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults. In this article, we performed a systematic review of studies investigating gene × environment interactions in BD and schizophrenia spectrum phenotypes. In the majority of studies from this field, interacting effects of variation in genes encoding catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein 5 (FKBP5) have been explored. Almost consistently, these studies revealed that polymorphisms in COMT, BDNF, and FKBP5 genes might interact with early life stress and cannabis abuse or dependence, influencing various outcomes of schizophrenia spectrum disorders and BD. Other interactions still require further replication in larger clinical and non-clinical samples. In addition, future studies should address the direction of causality and potential mechanisms of the relationship between gene × environment interactions and various categories of outcomes in schizophrenia and BD.

AB - Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults. In this article, we performed a systematic review of studies investigating gene × environment interactions in BD and schizophrenia spectrum phenotypes. In the majority of studies from this field, interacting effects of variation in genes encoding catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein 5 (FKBP5) have been explored. Almost consistently, these studies revealed that polymorphisms in COMT, BDNF, and FKBP5 genes might interact with early life stress and cannabis abuse or dependence, influencing various outcomes of schizophrenia spectrum disorders and BD. Other interactions still require further replication in larger clinical and non-clinical samples. In addition, future studies should address the direction of causality and potential mechanisms of the relationship between gene × environment interactions and various categories of outcomes in schizophrenia and BD.

KW - Journal Article

KW - Review

KW - Bipolar Disorder/genetics

KW - Genetic Variation

KW - Genetic Predisposition to Disease

KW - Genetic Association Studies

KW - Humans

KW - Environment

KW - Gene-Environment Interaction

KW - Schizophrenia/genetics

U2 - 10.1007/s12035-017-0708-y

DO - 10.1007/s12035-017-0708-y

M3 - SCORING: Review article

C2 - 28822116

VL - 55

SP - 5075

EP - 5100

JO - MOL NEUROBIOL

JF - MOL NEUROBIOL

SN - 0893-7648

IS - 6

ER -