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Association Between Genetic Risk for Type 2 Diabetes and Structural Brain Connectivity in Major Depressive Disorder

Published:March 05, 2021DOI:https://doi.org/10.1016/j.bpsc.2021.02.010

      Abstract

      Background

      Major depressive disorder (MDD) and type 2 diabetes mellitus (T2D) are known to share clinical comorbidity and to have genetic overlap. Besides their shared genetics, both diseases seem to be associated with alterations in brain structural connectivity and impaired cognitive performance, but little is known about the mechanisms by which genetic risk of T2D might affect brain structure and function and if they do, how these effects could contribute to the disease course of MDD.

      Methods

      This study explores the association of polygenic risk for T2D with structural brain connectome topology and cognitive performance in 434 nondiabetic patients with MDD and 539 healthy control subjects.

      Results

      Polygenic risk score for T2D across MDD patients and healthy control subjects was found to be associated with reduced global fractional anisotropy, a marker of white matter microstructure, an effect found to be predominantly present in MDD-related fronto-temporo-parietal connections. A mediation analysis further suggests that this fractional anisotropy variation may mediate the association between polygenic risk score and cognitive performance.

      Conclusions

      Our findings provide preliminary evidence of a polygenic risk for T2D to be linked to brain structural connectivity and cognition in patients with MDD and healthy control subjects, even in the absence of a direct T2D diagnosis. This suggests an effect of T2D genetic risk on white matter integrity, which may mediate an association of genetic risk for diabetes and cognitive impairments.

      Keywords

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      Linked Article

      • Metabolic Traces in the Human Brain: Genetic Risk for Diabetes and Altered Structural Connectivity in Depression
        Biological Psychiatry: Cognitive Neuroscience and NeuroimagingVol. 7Issue 3
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          The long-term maintenance of energy homeostasis is a vital challenge for any organism, and energetic constraints play a pivotal role in the development of the brain along ontogenetic and evolutionary timescales (1). Likewise, individual differences in the efficiency of energy metabolism contribute to structural and functional alterations in the brain that may lead to a wide range of cognitive, behavioral, and affective consequences that can be detrimental for mental health and overall well-being.
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