title: Role of variation in the serotonin transporter protein gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder.
abstract: Bipolar disorder (BD) is associated with abnormalities of the ventral anterior cingulate cortex (vACC) and its connection sites, including the amygdala, which are key components of a corticolimbic neural system that subserves emotional regulation. Decreased functional connectivity from the vACC to the amygdala in healthy individuals is associated with the short 's' allele--as opposed to the long 'l' allele--of a well-known serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4), as are features of BD. This study tests the hypothesis that the s allele influences dysfunction in the vACC-amygdala neural system in BD. A total of 30 euthymic individuals with BD (20 s carriers, 10 ll) and 48 healthy comparison (HC) participants (34 s, 14 ll) participated in an event-related functional magnetic resonance imaging scan while processing fearful, happy, or neutral faces. During fear and happy face processing, vACC activation was significantly lower in the BD compared to the HC group, and in s carriers compared to ll individuals within both the HC and BD groups, such that BD s carriers exhibited the greatest magnitude of vACC dysfunction. No significant differences were detected in amygdala activation. The findings suggest that the 5-HTTLPR s allele may contribute to a trait-related, genetically derived, neurobiological subgroup within BD characterized by prominent vACC dysfunction. Future treatment may be optimized for this BD subgroup by targeting the serotonergic system and the vACC.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA. maulik.p.shah@gmail.com
authors.forename: Maulik P
authors.initials: MP
authors.lastname: Shah
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Kalmar
authors.forename: Lara G
authors.initials: LG
authors.lastname: Chepenik
authors.forename: Karen
authors.initials: K
authors.lastname: Tie
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Monique M
authors.initials: MM
authors.lastname: Jones
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Blumberg
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology*; D004644:Emotions; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic; D044469:Racial Groups; D017422:Sequence Analysis, DNA; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D014796:Visual Perception
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins