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Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

ABSTRACT: Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1? genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1? allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1? allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit.

SUBMITTER: Gupta A

PROVIDER: S-EPMC4573367 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

Gupta Arpana A Labus Jennifer J Kilpatrick Lisa A LA Bonyadi Mariam M Ashe-McNalley Cody C Heendeniya Nuwanthi N Bradesi Sylvie S Chang Lin L Mayer Emeran A EA

Brain structure & function 20150130 3

Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors i ...[more]

PMID: 25630611

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Project description:IMPORTANCE:Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. OBJECTIVE:To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. DESIGN, SETTING, AND PARTICIPANTS:A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. EXPOSURES:Early childhood adversity. MAIN OUTCOMES AND MEASURES:The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. RESULTS:Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (? =?-.18; P =?.01) and higher GM volume in the precuneus (? =?.18; P =?.009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (? =?-.20; P =?.002). Early adversity was also associated with higher levels of internalizing symptoms (? =?.37; P <?.001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (? =?-.08; 95% CI, -0.14 to -0.01; P =?.02). CONCLUSIONS AND RELEVANCE:Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression.

Dataset Information

Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

Publications

Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

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