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

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

doi:10.1038/s41398-019-0559-6

Cited by 26 publications

(16 citation statements)

References 78 publications

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“…Recent investigations of gene pathway analysis 96 and PRSs 97 using GWAS data support the association of disturbances in insulin signaling with the pathophysiology of OCD. These findings were further validated in a rodent model of type 2 diabetes mellitus, which revealed increased compulsive-like behaviors and brain abnormalities previously associated with OCD 98 .…”

Section: Modeling Genetic Architecturesupporting

confidence: 59%

Cutting-edge genetics in obsessive-compulsive disorder

Saraiva¹,

Cappi²,

Simpson³

et al. 2020

Fac Rev

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This article reviews recent advances in the genetics of obsessive-compulsive disorder (OCD). We cover work on the following: genome-wide association studies, whole-exome sequencing studies, copy number variation studies, gene expression, polygenic risk scores, gene–environment interaction, experimental animal systems, human cell models, imaging genetics, pharmacogenetics, and studies of endophenotypes. Findings from this work underscore the notion that the genetic architecture of OCD is highly complex and shared with other neuropsychiatric disorders. Also, the latest evidence points to the participation of gene networks involved in synaptic transmission, neurodevelopment, and the immune and inflammatory systems in this disorder. We conclude by highlighting that further study of the genetic architecture of OCD, a great part of which remains to be elucidated, could benefit the development of diagnostic and therapeutic approaches based on the biological basis of the disorder. Studies to date revealed that OCD is not a simple homogeneous entity, but rather that the underlying biological pathways are variable and heterogenous. We can expect that translation from bench to bedside, through continuous effort and collaborative work, will ultimately transform our understanding of what causes OCD and thus how best to treat it.

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Section: Modeling Genetic Architecturesupporting

confidence: 59%

Cutting-edge genetics in obsessive-compulsive disorder

Saraiva¹,

Cappi²,

Simpson³

et al. 2020

Fac Rev

View full text Add to dashboard Cite

show abstract

“…There is a paucity of MRI studies in animal models of T2DM using imaging modalities commonly performed in the clinic. We know of only two such studies, one looking at ischemic vascular damage and axonal density following stroke in the high‐fat diet, streptozotocin‐treated Wistar rat (HFD/STZ), 7 and a second in the TALLYHO/JngJ (TH) mouse correlating white matter connectivity using DWI with compulsive behavior 53 . To address this shortcoming, we performed an exploratory study using VBM, DWI, and rsFC to interrogate the brain of the obese Bio‐Breeding Zucker diabetic (BBZDR/Wor) rat, a model of T2DM 52 .…”

Section: Introductionmentioning

confidence: 99%

Using multimodal MRI to investigate alterations in brain structure and function in the BBZDR/Wor rat model of type 2 diabetes

Lawson

Rentrup

Cai

et al. 2020

Anim Models and Exp Med

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BackgroundThis is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was hypothesized there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with noninvasive MRI.MethodsThe transgenic BBZDR/Wor rat, an animal model of T2MD, and age‐matched controls were studied for changes in brain structure using voxel‐based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting‐state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site‐specific data on over 168 different brain areas.ResultsThere was an overall reduction in brain volume focused primarily on the somatosensory cortex, cerebellum, and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus.ConclusionThe neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.

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“…Indeed, there is a paucity of MRI studies in animal models of T2DM using imaging modalities commonly performed in the clinic. We know of only two such studies, one looking at ischemic vascular damage and axonal density following stroke in the high-fat diet, streptozotocin treated Wistar rat (HFD/STZ) [16], and a second in the TALLYHO/JngJ (TH) mouse correlating white matter connectivity using DWI with compulsive behavior [17]. Hence, the major advantage of non-invasive animal imaging -to follow disease progression with the same imaging modalities used in the clinic -has not been exploited.…”

Section: Destruction Of Pancreatic Beta Cells Resulting In Insulin Dementioning

confidence: 99%

Using multimodal MRI to investigate alterations in brain structure and function in rats with type 2 diabetes.

Lawson¹,

Rentrup²,

Cai³

et al. 2020

Preprint

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Objectives This is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was assumed there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with non-invasive MRI. Methods The transgenic BBZDR/Wor rat, an animal model of T2MD, and age-matched controls were studied for changes in brain structure using voxel-based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site-specific data on over 168 different brain areas. Results There was an overall reduction in brain volume focused primarily on somatosensory cortex, cerebellum and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus. Conclusion Are the neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods common to the clinic, similar to those reported in T2DM patents? In comparison to the clinical findings, the data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.

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

Cited by 26 publications

References 78 publications

Cutting-edge genetics in obsessive-compulsive disorder

Cutting-edge genetics in obsessive-compulsive disorder

Using multimodal MRI to investigate alterations in brain structure and function in the BBZDR/Wor rat model of type 2 diabetes

Using multimodal MRI to investigate alterations in brain structure and function in rats with type 2 diabetes.

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