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 Sep 2019

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Compulsive Behavior
Anisotropy
Obsessive-Compulsive Disorder
Insulin
Brain
Magnetic Resonance Spectroscopy
Obsessive Behavior
Diffusion Tensor Imaging
Corpus Callosum
Gyrus Cinguli
Cerebellum
Type 2 Diabetes Mellitus
Fear
Glutathione
Blood Proteins
Anxiety
Glucose

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van de Vondervoort, I. I. G. M., Amiri, H., Bruchhage, M. M. K., Oomen, C. A., Rustogi, N., Cooper, J. D., ... Glennon, J. C. (2019). Converging evidence points towards a role of insulin signaling in regulating compulsive behavior. Translational Psychiatry, 9, 1-11. [225]. https://doi.org/10.1038/s41398-019-0559-6
van de Vondervoort, Ilse I.G.M. ; Amiri, Houshang ; Bruchhage, Muriel M.K. ; Oomen, Charlotte A. ; Rustogi, Nitin ; Cooper, Jason D. ; van Asten, Jack J.A. ; Heerschap, Arend ; Bahn, Sabine ; Williams, Steven C.R. ; Buitelaar, Jan K. ; Poelmans, Geert ; Glennon, Jeffrey C. / Converging evidence points towards a role of insulin signaling in regulating compulsive behavior. In: Translational Psychiatry. 2019 ; Vol. 9. pp. 1-11.
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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.",
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van de Vondervoort, IIGM, Amiri, H, Bruchhage, MMK, Oomen, CA, Rustogi, N, Cooper, JD, van Asten, JJA, Heerschap, A, Bahn, S, Williams, SCR, Buitelaar, JK, Poelmans, G & Glennon, JC 2019, 'Converging evidence points towards a role of insulin signaling in regulating compulsive behavior' Translational Psychiatry, vol. 9, 225, pp. 1-11. https://doi.org/10.1038/s41398-019-0559-6

Converging evidence points towards a role of insulin signaling in regulating compulsive behavior. / van de Vondervoort, Ilse I.G.M.; Amiri, Houshang; Bruchhage, Muriel M.K.; Oomen, Charlotte A.; Rustogi, Nitin; Cooper, Jason D.; van Asten, Jack J.A.; Heerschap, Arend; Bahn, Sabine; Williams, Steven C.R.; Buitelaar, Jan K.; Poelmans, Geert; Glennon, Jeffrey C.

In: Translational Psychiatry, Vol. 9, 225, 12.09.2019, p. 1-11.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Oomen, Charlotte A.

AU - Rustogi, Nitin

AU - Cooper, Jason D.

AU - van Asten, Jack J.A.

AU - Heerschap, Arend

AU - Bahn, Sabine

AU - Williams, Steven C.R.

AU - Buitelaar, Jan K.

AU - Poelmans, Geert

AU - Glennon, Jeffrey C.

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van de Vondervoort IIGM, Amiri H, Bruchhage MMK, Oomen CA, Rustogi N, Cooper JD et al. Converging evidence points towards a role of insulin signaling in regulating compulsive behavior. Translational Psychiatry. 2019 Sep 12;9:1-11. 225. https://doi.org/10.1038/s41398-019-0559-6