Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, which selectively block serotonin transporter (5-HTT) activity, are widely used in the treatment of depression and anxiety disorders. Numerous neuroimaging studies have examined the effects of SSRIs on emotional processes. However, there are considerable inter-individual differences in SSRI effect, and a recent meta-analysis further revealed discrepant effects of acute SSRI administration on neural responses to negative emotions in healthy adults.


OBJECTIVE
We examined how a variant of the serotonin-transporter polymorphism (5-HTTLPR), which affects the expression and function of 5-HTT, influenced the acute effects of an SSRI (citalopram) on emotion-related brain activity in healthy adults.


METHODS
Combining genetic neuroimaging, pharmacological technique and a psychological paradigm of emotion recognition, we scanned the short/short (s/s) and long/long (l/l) variants of 5-HTTLPR during perception of fearful, happy and neutral facial expressions after the acute administration of an SSRI (i.e. 30 mg citalopram administered orally) or placebo administration.


RESULTS
We found that 5-HTTLPR modulated the acute effects of citalopram on neural responses to negative emotions. Specifically, relative to placebo, citalopram increased amygdala and insula activity in l/l but not s/s homozygotes during perception of fearful faces. Similar analyses of brain activity in response to happy faces did not show any significant effects.


CONCLUSIONS
Our combined pharmacogenetic and functional imaging results provide a neurogenetic mechanism for discrepant acute effects of SSRIs.
Yina Ma, PhD, Department of Psychology, Peking University, China, and Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, USA; Bingfeng Li, BS, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chenbo Wang, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Wenxia Zhang, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Yi Rao, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Shihui Han, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Yina
Y
Ma
Yina Ma, PhD, Department of Psychology, Peking University, China, and Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, USA; Bingfeng Li, BS, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chenbo Wang, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Wenxia Zhang, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Yi Rao, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Shihui Han, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Bingfeng
B
Li
Yina Ma, PhD, Department of Psychology, Peking University, China, and Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, USA; Bingfeng Li, BS, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chenbo Wang, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Wenxia Zhang, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Yi Rao, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Shihui Han, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Chenbo
C
Wang
Yina Ma, PhD, Department of Psychology, Peking University, China, and Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, USA; Bingfeng Li, BS, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chenbo Wang, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Wenxia Zhang, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Yi Rao, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Shihui Han, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Wenxia
W
Zhang
Yina Ma, PhD, Department of Psychology, Peking University, China, and Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, USA; Bingfeng Li, BS, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chenbo Wang, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Wenxia Zhang, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Yi Rao, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Shihui Han, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Yi
Y
Rao
Yina Ma, PhD, Department of Psychology, Peking University, China, and Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, USA; Bingfeng Li, BS, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chenbo Wang, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Wenxia Zhang, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Yi Rao, PhD, Peking-Tsinghua Center for Life Sciences at School of Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Shihui Han, PhD, Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
Shihui
S
Han
D000293:Adolescent; D000483:Alleles; D000679:Amygdala / Q000503:physiopathology*; D015283:Citalopram / Q000008:administration & dosage*; D004644:Emotions / Q000187:drug effects*; D005149:Facial Expression; D005239:Fear / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000187:drug effects*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D055815:Young Adult
D015283:Citalopram; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors