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 h...

Full description

Saved in:
Bibliographic Details
Published in:Trends in neurosciences (Regular ed.) 2012-07, Vol.35 (7), p.395-402
Main Authors: Jasinska, Agnes J, Lowry, Christopher A, Burmeister, Margit
Format: Article
Language:English
Subjects:
5-HTTLPR
Adult and adolescent clinical studies
amygdala
Animals
Biological and medical sciences
Depression
Depression - etiology
dorsal raphe nucleus
Fundamental and applied biological sciences. Psychology
Gene-Environment Interaction
gene-environment interactions
General aspects. Models. Methods
Genes
Genetic Predisposition to Disease - genetics
Humans
Medical sciences
Mental depression
Mood disorders
Neurology
Neurosciences
Neurotransmitters
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Raphe Nuclei
Serotonin
Serotonin Plasma Membrane Transport Proteins - genetics
Stress
Stress, Psychological - genetics
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0166-2236
1878-108X
1878-108X
DOI:10.1016/j.tins.2012.01.001