Association between genetic risk for type 2 diabetes and structural brain connectivity in major depressive disorder

Jonathan Repple, Amelie König, Siemon C de Lange, Nils Opel, Ronny Redlich, Susanne Meinert, Dominik Grotegerd, Marco Mauritz, Tim Hahn, Tiana Borgers, Elisabeth J Leehr, Nils Winter, Janik Goltermann, Verena Enneking, Stella M Fingas, Hannah Lemke, Lena Waltemate, Katharina Dohm, Maike Richter, David M A MehlerVincent Holstein, Marius Gruber, Igor Nenadic, Axel Krug, Katharina Brosch, Simon Schmitt, Frederike Stein, Tina Meller, Andreas Jansen, Olaf Steinsträter, Azmeraw T Amare, Tilo Kircher, Bernhard T Baune, Martijn P van den Heuvel, Udo Dannlowski

Research output: Contribution to JournalArticleAcademicpeer-review

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BACKGROUND: Major depressive disorder (MDD) and type 2 diabetes (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 so, 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 MDD patients and 539 healthy controls.

RESULTS: Polygenic risk score for T2D across MDD patients and healthy controls 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 FA variation may mediate the association between PGS 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 MDD patients and healthy controls, 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.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalBiological Psychiatry : Cognitive Neuroscience and Neuroimaging
Issue number3
Early online date5 Mar 2021
Publication statusPublished - Mar 2022


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