HTR5A and major depressive disorder: Indeed, SSRIs have historically been used to treat disorders of negative affect, including depression and anxiety.143 In both healthy and depressed individuals, chronic SSRI administration leads to a positive shift in valence processing, possibly via amygdalar circuits.139,144 Further studies investigating SSRI administration demonstrate that SSRI treatments (increasing levels of 5-HT in the synaptic cleft) enhance LTP from BU regions communicating to the mPFC.141 These results suggest that excess 5-HT signaling acutely mediates plasticity in mPFC.