Impact of the HTR3A gene with early life trauma on emotional brain networks and depressed mood.
BACKGROUND
The risk for mental illnesses such as depression is increasingly conceptualized as the product of gene-environment interactions and their impact on brain structure and function. The role of serotonin 3A receptor gene (HTR3A -42C>T polymorphism) and its interaction with early life stress (ELS) was investigated in view of the receptor's localization to brain regions central to emotion processing.


METHODS
Fronto-limbic grey matter (GM) loss was measured using magnetic resonance imaging and assessed using voxel-based morphometry analysis in 397 nonclinical individuals from the Brain Resource International Database. Negative mood symptoms were also assessed.


RESULTS
The HTR3A CC genotype group, compared to the T carriers, demonstrated comparative loss to GM in hippocampal structures, which extended to the frontal cortices for those CC genotype individuals also exposed to ELS. Elevations in depressed mood were also evident.


CONCLUSIONS
These findings suggest that the HTR3A CC genotype may be associated with alterations in brain structures central to emotion processing, particularly when exposed to stress, and further highlight the potential role of the serotonin system in the pathophysiology of affective disorders. In contrast, those individuals with the T allele, in particular the TT genotype, may be more protected from such alterations combined with minimal exposure to ELS events.
Gatt
Justine M
JM
The Brain Dynamics Center, Westmead Millennium Institute & Discipline of Psychiatry, University of Sydney at Westmead Hospital, New South Wales, Australia.
Williams
Leanne M
LM
Schofield
Peter R
PR
Dobson-Stone
Carol
C
Paul
Robert H
RH
Grieve
Stuart M
SM
Clark
C Richard
CR
Gordon
Evian
E
Nemeroff
Charles B
CB
D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003866:Depressive Disorder / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008032:Limbic System / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D012931:Social Environment
C509409:HTR3A protein, human; D044406:Receptors, Serotonin, 5-HT3