Variation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses during Emotional Stimulus Processing

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dc.contributor.authorHsu, David T.
dc.contributor.authorMickey, Brian J.
dc.contributor.authorLangenecker, Scott A.
dc.contributor.authorHeitzeg, Mary M.
dc.contributor.authorLove, Tiffany M.
dc.contributor.authorWang, Heng
dc.contributor.authorKennedy, Susan E.
dc.contributor.authorPecina, Marta
dc.contributor.authorShafir, Tal
dc.contributor.authorHodgkinson, Colin A.
dc.contributor.authorEnoch, Mary-Anne
dc.contributor.authorGoldman, David
dc.contributor.authorZubieta, Jon-Kar
dc.contributor.otherUniversity of Michigan
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherNational Institutes of Health (NIH) - USA
dc.contributor.otherNIH National Institute on Alcohol Abuse & Alcoholism (NIAAA)
dc.date.accessioned2023-09-28T22:04:13Z
dc.date.available2023-09-28T22:04:13Z
dc.date.issued2012
dc.description.abstractThe corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-homozygotes) in the right middle temporal/angular gyrus while subjects were viewing negative versus neutral words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A-carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50) in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life stress, personality traits, and levels of negative memory bias were associated with brain activity depending on genotype. Results from healthy controls and a preliminary sample of MDD participants show that CRHR1 single nucleotide polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting a potential mechanism of vulnerability for the development of MDD.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationHsu, D. T., Mickey, B. J., Langenecker, S. A., Heitzeg, M. M., Love, T. M., Wang, H., Kennedy, S. E., Peciña, M., Shafir, T., Hodgkinson, C. A., Enoch, M.-A., Goldman, D., & Zubieta, J.-K. (2012). Variation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses during Emotional Stimulus Processing. In The Journal of Neuroscience (Vol. 32, Issue 9, pp. 3253–3260). Society for Neuroscience. https://doi.org/10.1523/jneurosci.5533-11.2012
dc.identifier.doi10.1523/JNEUROSCI.5533-11.2012
dc.identifier.orcidhttps://orcid.org/0000-0002-1724-5405
dc.identifier.orcidhttps://orcid.org/0000-0002-7932-5494
dc.identifier.orcidhttps://orcid.org/0000-0002-1724-5405
dc.identifier.orcidhttps://orcid.org/0000-0001-9299-3190
dc.identifier.orcidhttps://orcid.org/0000-0002-7847-7680
dc.identifier.orcidhttps://orcid.org/0000-0002-5365-8119
dc.identifier.orcidhttps://orcid.org/0000-0002-6737-2971
dc.identifier.urihttps://ir.ua.edu/handle/123456789/12268
dc.languageEnglish
dc.language.isoen_US
dc.publisherSociety for Neuroscience
dc.subjectFACTOR-LIKE IMMUNOREACTIVITY
dc.subjectSTRESSFUL LIFE EVENTS
dc.subjectMAJOR DEPRESSION
dc.subjectADULT DEPRESSION
dc.subjectANTIDEPRESSANT TREATMENT
dc.subjectCHILDHOOD MALTREATMENT
dc.subjectBEHAVIORAL ACTIVATION
dc.subjectMACAQUE MONKEYS
dc.subjectSUICIDE VICTIMS
dc.subjectPRIMATE BRAIN
dc.subjectNeurosciences
dc.titleVariation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses during Emotional Stimulus Processingen_US
dc.typeArticle
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