Allelic variation in 5-HTTLPR and the effects

antidepressants and have been used to treat mood disorders, such as depression and anxiety disorder. Selective serotonin reuptake inhibitors such as citalopram selectively block serotonin transporter (5-HTT) activity, inhibit the reuptake of serotonin (5-HT) into the presynaptic cell and lead to increasing extracellular levels of 5HT. Although clinical trials have shown that SSRIs typically have a delay of several weeks in the onset of their clinical effects, SSRI effects can occur soon after their administration. The early changes in emotional processing that occur after the acute administration of an SSRI contribute to later mood improvements. Therefore, understanding the neural mechanisms underlying the acute effects of SSRIs is important for decisions about long-term treatment. However, recent neuroimaging studies have reported inconsistent acute effects of SSRIs on neural responses in emotion-related brain regions such as the amygdala, whose hyperactivity has been suggested as an endophenotype of anxiety disorder and major depression. Twelve functional magnetic resonance imaging (fMRI) studies have examined the acute effects of SSRIs (single SSRI administration) on neural responses to negative emotions, while eight fMRI studies have examined acute effects of SSRI administration on neural response to positive emotions. Among these studies, four reported increased amygdala response whereas eight reported decreased amygdala response to negative emotions after SSRI v. placebo administration. Two studies reported increased amygdala response to positive emotions, whereas six studies did not show SSRI effects on amygdala response to positive emotions. Moreover, our recent meta-analysis revealed that the acute effects of antidepressants on positive emotions did not show any convergent activation in healthy adults. Acute antidepressant administration showed discrepant effects on neural responses to negative emotions. Specifically, single antidepressant administration led to convergent increases as well as decreases in a similar neural network underlying negative emotions. Although age, gender or disease conditions may contribute to individual differences in psychometric outcome and discrepant SSRI effects on amygdala response, the genetic structure of individuals also affects drug responses. A sodiumdependent serotonin-transporter-linked polymorphic region (5-HTTLPR), which influences the expression and function of 5-HTT, may be implicated in SSRI efficacy. For example, major depression patients with the long (l) allele of 5-HTTLPR showed better responses to SSRI treatment compared to homozygotes for the short variant (s/s) of 5-HTTLPR. However, it remains unknown whether and how 5-HTTLPR polymorphism affects the acute effects of SSRIs on brain activity.