Antidepressant drug administration modulates emotional processing in depressed patients very early in treatment, before changes occur in mood and symptoms. This effect may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. It also suggests a mechanism of action compatible with cognitive theories of depression.

These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression. The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism.

N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA's roles in neuronal super-additivity and as crucial for evidence integration for decisions.

Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (w 2 ¼ 6.9, po0.03). This result emerged in the whole sample, but was related only to female patients (w 2 ¼ 7.6, po0.02). The presence of the long allelic variant was associated with a better response of panic attacks while was not significantly associated with the response of anticipatory anxiety or phobic avoidance. In conclusion, paroxetine efficacy in PD seems to be related to allelic variation within the promoter of the 5-HTT gene in female subjects. This gender effect might be related to the genomic effects of sex hormones. Understanding the interaction between gender and genes coding for structures target of psychotropic drugs could help to individualize the pharmacological treatment of PD.