title: Effects of a alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression.
abstract: Alterations in processing of emotionally salient information have been reported in individuals with major depressive disorder (MDD). Evidence suggests a role for noradrenaline in the regulation of a cortico-limbic-striatal circuit that has also been implicated in the pathophysiology of MDD. Herein, we studied the physiological consequences of a common coding polymorphism of the gene for the alpha(2C)-adrenoreceptor (AR) subtype--the deletion of four consecutive amino acids at codons 322-325 of the alpha2C-AR (alpha2CDel322-325-AR) in medication-free, remitted individuals with MDD (rMDD), and healthy control subjects. After injection of 10 mCi of H2(15)O, positron emission tomography (PET) measures of neural activity were acquired while subjects were viewing unmasked sad, happy, and fearful faces. The neural responses to sad facial expressions were increased in the amygdala and decreased in the left ventral striatum in rMDD patients relative to healthy control subjects. Furthermore, we report that rMDD carriers of one or two copies of the alpha2CDel322-325-AR exhibit greater amygdala as well as pregenual and subgenual anterior cingulate gyrus neuronal activity in response to sad faces than healthy alpha2CDel322-325-AR carriers and rMDD noncarriers. These results suggest that the alpha2CDel322-325-AR confers a change in brain function implicating this alpha2-AR subtype into the pathophysiology of MDD.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA. alexander.neumeister@yale.edu
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.forename: Inna
authors.initials: I
authors.lastname: Belfer
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Shannan
authors.initials: S
authors.lastname: Henry
authors.forename: Omer
authors.initials: O
authors.lastname: Bonne
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism; D001479:Basal Ganglia / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010775:Photic Stimulation / Q000379:methods; D011110:Polymorphism, Genetic / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000379:methods; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: C547774:ADRA2C protein, human; D018341:Receptors, Adrenergic, alpha-2