Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network

作者：Ma Yina^*; Li Bingfeng; Wang Chenbo; Zhang Wenxia; Rao Yi; Han Shihui

来源：The British Journal of Psychiatry, 2015, 206(5): 385-392.

DOI：10.1192/bjp.bp.114.150128

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.
Aims
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.
Method
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.

• 出版日期2015-5
• 单位北京大学