Background
A polymorphism in the serotonin transporter (5-HTT) gene modulates the association
between adverse early experiences and risk for major depression in adulthood. Although
human imaging studies have begun to elucidate the neural circuits involved in the
5-HTT × environment risk factor, a molecular understanding of this phenomenon is lacking.
Such an understanding might help to identify novel targets for the diagnosis and therapy
of mood disorders. To address this need, we developed a gene-environment screening
paradigm in the mouse.
Methods
We established a mouse model in which a heterozygous null mutation in 5-HTT moderates
the effects of poor maternal care on adult anxiety and depression-related behavior.
Biochemical analysis of brains from these animals was performed to identify molecular
substrates of the gene, environment, and gene × environment effects.
Results
Mice experiencing low maternal care showed deficient γ-aminobutyric acid–A receptor
binding in the amygdala and 5-HTT heterozygous null mice showed decreased serotonin
turnover in hippocampus and striatum. Strikingly, levels of brain-derived neurotrophic
factor (BDNF) messenger RNA in hippocampus were elevated exclusively in 5-HTT heterozygous
null mice experiencing poor maternal care, suggesting that developmental programming
of hippocampal circuits might underlie the 5-HTT × environment risk factor.
Conclusions
These findings demonstrate that serotonin plays a similar role in modifying the long-term
behavioral effects of rearing environment in diverse mammalian species and identifies
BDNF as a molecular substrate of this risk factor.
Key Words
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Article info
Publication history
Published online: October 22, 2007
Accepted:
August 24,
2007
Received in revised form:
July 19,
2007
Received:
April 7,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
