Converging evidence points towards a role of insulin signaling in regulating compulsive behavior

Ilse I.G.M. van de Vondervoort, Houshang Amiri, Muriel M.K. Bruchhage, Charlotte A. Oomen, Nitin Rustogi, Jason D. Cooper, Jack J.A. van Asten, Arend Heerschap, Sabine Bahn, Steven C.R. Williams, Jan K. Buitelaar, Geert Poelmans, Jeffrey C. Glennon

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior.

Original languageEnglish
Article number225
Pages (from-to)1-11
Number of pages11
JournalTranslational Psychiatry
Volume9
DOIs
Publication statusPublished - 12 Sept 2019

Funding

The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreements n°278948 (TACTICS), n°305697 (OPTIMISTIC), and n°603016 (MATRICS). This funding organization has had no involvement with the conception, design, data analysis and interpretation, review and/or any other aspects relating to this paper. In addition, S.C.R. Williams and M.M.K. Bruchhage would like to express their deepest gratitude to the NIHR Biomedical Research Centre for Mental Health at the South London and the Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London for their on-going support of our translational imaging research program. In addition, we would like to thank Ward De Witte for assistance with the False Discovery Rate (FDR) analyses. Lastly, we thank Andor Veltien for help with the MR experiments and keeping the MR instruments in excellent condition, and the staff at the animal facility for their support.

FundersFunder number
FP7/2007
Seventh Framework Programme305697, 278948, 603016
Seventh Framework Programme

    Fingerprint

    Dive into the research topics of 'Converging evidence points towards a role of insulin signaling in regulating compulsive behavior'. Together they form a unique fingerprint.

    Cite this