Figure 5

Proposed actions of 5-HT1A C(-1019)G genotype in normal vs. depressed subjects. In normal subjects containing homozygous HTR1A C/C (-1019) genotype, 5-HT neurons fire at their normal rate (red action potentials), releasing 5-HT (red dots) at the synapse for activation of receptors (ovals), and to a lesser degree at the raphe cell body to restrain neuronal activity by negative feedback through the 5-HT1A autoreceptor (yellow ovals). In the G/G genotype and in depressed subjects, 5-HT1A autoreceptor expression is increased which would reduce neuronal firing and 5-HT release, while post-synaptic 5-HT1A receptors are reduced in certain regions, which would decrease response to 5-HT release. Normal subjects with the G/G genotype have a lesser increase of 5-HT1A autoreceptors, and are able to compensate for the effect of the G/G genotype on transcription.