title: 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-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β 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.
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA. aagupta9@gmail.com.|David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA. aagupta9@gmail.com.|Division of Digestive Diseases, University of California Los Angeles (UCLA), Los Angeles, USA. aagupta9@gmail.com.
authors: Arpana
authors: A
authors: Gupta
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.|David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA.|Division of Digestive Diseases, University of California Los Angeles (UCLA), Los Angeles, USA.
authors: Jennifer
authors: J
authors: Labus
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.|David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA.|Division of Digestive Diseases, University of California Los Angeles (UCLA), Los Angeles, USA.
authors: Lisa A
authors: LA
authors: Kilpatrick
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.
authors: Mariam
authors: M
authors: Bonyadi
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.
authors: Cody
authors: C
authors: Ashe-McNalley
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.
authors: Nuwanthi
authors: N
authors: Heendeniya
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.|David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA.|Division of Digestive Diseases, University of California Los Angeles (UCLA), Los Angeles, USA.
authors: Sylvie
authors: S
authors: Bradesi
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.|David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA.|Division of Digestive Diseases, University of California Los Angeles (UCLA), Los Angeles, USA.
authors: Lin
authors: L
authors: Chang
authors: Oppenheimer Center for Neurobiology of Stress, and Pain and Interoception Network (PAIN), University of California Los Angeles (UCLA), CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, CA, 90095-7378, USA.|David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA.|Division of Digestive Diseases, University of California Los Angeles (UCLA), Los Angeles, USA.|Ahmanson-Lovelace Brain Mapping Center, University of California Los Angeles (UCLA), Los Angeles, USA.
authors: Emeran A
authors: EA
authors: Mayer
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D004660:Encephalitis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000473:pathology*; D006304:Health Status; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid
keywords: Cortical thickness; Early adverse life events; Functional somatic pain; Glucocorticoids; NF-κB; Proinflammatory cytokines; Subgenual anterior cingulate cortex
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