Role of variation in the serotonin transporter protein gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder.
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.
Shah
Maulik P
MP
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA. maulik.p.shah@gmail.com
Wang
Fei
F
Kalmar
Jessica H
JH
Chepenik
Lara G
LG
Tie
Karen
K
Pittman
Brian
B
Jones
Monique M
MM
Constable
R Todd
RT
Gelernter
Joel
J
Blumberg
Hilary P
HP
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
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins