The cumulative effect of genetic polymorphisms on depression and brain structural integrity

Milutin Kostic, Elisa Canu, Federica Agosta, Ana Munjiza, Ivana Novakovic, Valerija Dobricic, Pilar Maria Ferraro, Vera Miler Jerkovic, Tatjana Pekmezovic, Dusica Lecic Tosevski, Massimo Filippi

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)2173 - 2184
Number of pages12
JournalHuman Brain Mapping
Volume37
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Genetic Polymorphisms
Major Depressive Disorder
Depression
Brain
Corpus Callosum
Occipital Lobe
Parietal Lobe
Brain-Derived Neurotrophic Factor
Genes
Homozygote
Genetic Testing
Frontal Lobe
Amygdala
Hippocampus
Magnetic Resonance Imaging
White Matter

Keywords

  • Accumulation model
  • Cortical thickness
  • Functional polymorphisms
  • Major depression disorder
  • Tractography

ASJC Scopus subject areas

  • Clinical Neurology
  • Anatomy
  • Neurology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

The cumulative effect of genetic polymorphisms on depression and brain structural integrity. / Kostic, Milutin; Canu, Elisa; Agosta, Federica; Munjiza, Ana; Novakovic, Ivana; Dobricic, Valerija; Maria Ferraro, Pilar; Miler Jerkovic, Vera; Pekmezovic, Tatjana; Lecic Tosevski, Dusica; Filippi, Massimo.

In: Human Brain Mapping, Vol. 37, No. 6, 01.06.2016, p. 2173 - 2184.

Research output: Contribution to journalArticle

Kostic, M, Canu, E, Agosta, F, Munjiza, A, Novakovic, I, Dobricic, V, Maria Ferraro, P, Miler Jerkovic, V, Pekmezovic, T, Lecic Tosevski, D & Filippi, M 2016, 'The cumulative effect of genetic polymorphisms on depression and brain structural integrity', Human Brain Mapping, vol. 37, no. 6, pp. 2173 - 2184. https://doi.org/10.1002/hbm.23165
Kostic, Milutin ; Canu, Elisa ; Agosta, Federica ; Munjiza, Ana ; Novakovic, Ivana ; Dobricic, Valerija ; Maria Ferraro, Pilar ; Miler Jerkovic, Vera ; Pekmezovic, Tatjana ; Lecic Tosevski, Dusica ; Filippi, Massimo. / The cumulative effect of genetic polymorphisms on depression and brain structural integrity. In: Human Brain Mapping. 2016 ; Vol. 37, No. 6. pp. 2173 - 2184.
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