Open Access
The cumulative effect of genetic polymorphisms on depression and brain structural integrity
Author(s) -
Kostic Milutin,
Canu Elisa,
Agosta Federica,
Munjiza Ana,
Novakovic Ivana,
Dobricic Valerija,
Ferraro Pilar,
Miler Jerkovic Vera,
Pekmezovic Tatjana,
Lecic Tosevski Dusica,
Filippi Massimo
Publication year - 2016
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.23165
Subject(s) - corpus callosum , white matter , cortex (anatomy) , neuroscience , prefrontal cortex , hippocampus , major depressive disorder , hippocampal formation , medicine , psychology , amygdala , magnetic resonance imaging , radiology , cognition
Abstract In major depressive disorder (MDD), the need to study multiple‐gene effect on brain structure is emerging. Our aim was to assess the effect of accumulation of specific SERT, BDNF and COMT gene functional polymorphisms on brain structure in MDD patients. Seventy‐seven MDD patients and 66 controls underwent a clinical assessment, genetic testing and MRI scan. Compared with controls, patients were more BDNF ‐Val homozygotes, COMT ‐Met carriers and SERT ‐L' carriers. Thus, subjects were split into three groups: 1. High‐frequency susceptibility polymorphism group (hfSP, subjects with all three SPs); 2. Intermediate‐frequency SP group (ifSP, two SPs); and 3. Low‐frequency SP group (lfSP, one/none SP). Cortical thickness, volumetry of hippocampus, amygdala and subcortical structures, and white matter (WM) tract integrity were assessed. Compared to controls, hfSP patients showed thinning of the middle frontal cortex bilaterally, left frontal pole, and right lateral occipital cortex, and smaller hippocampal volume bilaterally; and both hfSP and lfSP patient groups showed thinning of the left inferior parietal cortex and reduced WM integrity of the corpus callosum. Compared to patients, hfSP controls showed greater integrity of the fronto‐occipital cortices and corpus callosum. We showed that cortical prefrontal and occipital damage of MDD patients is modulated by the SP accumulation, while damage to the parietal cortex and corpus callosum seem to be independent of genetic accumulation. HfSP controls may experience protective mechanisms leading to a preserved integrity of critical cortical and WM regions. Investigating the effect of multiple genes is promising to understand the pathological mechanisms underlying MDD. Hum Brain Mapp 37:2173–2184, 2016 . © 2016 Wiley Periodicals, Inc.