Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression.
Reports of gene-environment interactions (GxE) between the serotonin transporter gene and stress on risk of depression have generated both excitement and controversy. The controversy persists in part because a mechanistic account of this GxE on serotonergic neurotransmission and risk of depression has been lacking. In this Opinion, we draw on recent discoveries in the functional neuroanatomy of the serotonergic dorsal raphe nucleus (DR) to propose such a mechanistic account. We argue that genetically produced variability in serotonin reuptake during stressor-induced raphe-raphe interactions alters the balance in the amygdala-ventromedial prefrontal cortex (VMPFC)-DR circuitry underlying stressor reactivity and emotion regulation. In particular, the recently characterized stressor-responsive serotonergic interneurons originating from the dorsolateral DR may hold a key to unlocking the GxE mechanism of depression.
Department of Psychology, University of Michigan, Ann Arbor, Michigan, USA. jasinska@umich.edu
Agnes J
AJ
Jasinska
Christopher A
CA
Lowry
Margit
M
Burmeister
D000818:Animals; D003863:Depression / Q000209:etiology*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D011903:Raphe Nuclei; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*
D050486:Serotonin Plasma Membrane Transport Proteins