title: Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing.
abstract: The 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.
authors.affiliation: Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Hsu
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Mickey
authors.forename: Scott A
authors.initials: SA
authors.lastname: Langenecker
authors.forename: Mary M
authors.initials: MM
authors.lastname: Heitzeg
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Love
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kennedy
authors.forename: Marta
authors.initials: M
authors.lastname: Peciña
authors.forename: Tal
authors.initials: T
authors.lastname: Shafir
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000235:genetics / Q000523:psychology; D004644:Emotions / Q000502:physiology*; D005260:Female; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1