@article{66a0e995468b4b8d8be024d26bbc86e5,
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.",
keywords = "Bipolar disorder, Genetic polymorphism, Gyrus cinguli, Magnetic resonance imaging, Serotonin, Serotonin transporter promoter polymorphism",
author = "Shah, {Maulik P.} and Fei Wang and Kalmar, {Jessica H.} and Chepenik, {Lara G.} and Karen Tie and Brian Pittman and Jones, {Monique M.} and Constable, {R. Todd} and Joel Gelernter and Blumberg, {Hilary P.}",
note = "Funding Information: Dr Gelernter has received financial support or compensation for the following: related to consultation for Columbia University, the Thailand Center for Excellence for Life Sciences (TCELS), the University of CT Health Center, and NIH; related to grant reviews for the National Institutes of Health; and related to academic lectures and editorial functions in various scientific venues (including the ACNP). Funding Information: This article is dedicated to Ms Kathleen Colonese who was devoted to helping those suffering from psychiatric illnesses and whose kindness to colleagues and participants alike touched us all. We give thanks to all of the participants in this study, and hope that this work may one day contribute to helping those living with bipolar disorder. We thank the nurses of the VA CT Healthcare System Biostudies Unit Ms Angelina M Genovese RNC, MBA, Ms Elizabeth O{\textquoteright}Donnell RN, and Ms Brenda Breault RN, BSN. We also thank Ms Ann Marie Lacobelle, MS for her assistance in genotyping. We acknowledge the help and support of all members of the Mood Disorders Laboratory at Yale including Ms Erin Edmiston, Ms Linda Spencer, Ms Allison McDonough, Ms Gina Williams, and Mr Thomas Flanagan. We also appreciate the efforts of the staff at the Yale Magnetic Resonance Research Center including Ms Cheryl Lacadie, Ms Karen Martin, Ms Terry Hickey, and Ms Hedy Sarofin. This work was supported by grants from the Howard Hughes Medical Institute (MPS), the Department of Veterans Affairs Research Career Development (HPB), Merit Review (HPB and JG) and Research Enhancement Award Program (REAP)(HPB and JG) Awards, the National Institute of Mental Health R01MH69747 (HPB), R01MH070902 (HPB), K24 15105 (JG), T32MH14276 (LGC and JHK), CTSA Grant Number UL1 RR0249139 from the NIH National Center for Research Resources (NCRR), the National Alliance for Research on Schizophrenia and Depression (Great Neck, NY) (HPB, JHK), The Attias Family Foundation (HPB), Marcia Simon Kaplan (JHK), The Ethel F Donaghue Women{\textquoteright}s Investigator Program at Yale (New Haven, CT) (HPB) and the Klingenstein Foundation (JHK).",
year = "2009",
month = apr,
doi = "10.1038/npp.2008.204",
language = "English (US)",
volume = "34",
pages = "1301--1310",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "5",
}