Insulin dysfunction and allostatic load in bipolar disorder

Brietzke, Elisa; Kapczinski, Flávio; Grassi‐Oliveira, Rodrigo; Grande, Íria; Vieta, Eduard; McIntyre, Roger S.

doi:10.1586/ern.10.185

Cited by 55 publications

(44 citation statements)

References 141 publications

(113 reference statements)

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“…Furthermore, the fact that the changes extended beyond the hippocampus to cortical regions makes them less likely to be related to stress associated with T2DM. Perhaps these alterations are predominantly associated with impaired insulin signaling, with resulting withdrawal of trophic factors, inhibition of insulin-responsive gene expression and impaired mitochondrial energy metabolism, which increases oxidative stress (Brietzke et al, 2011;Hajek et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

Hájek

Calkin

Blagdon

et al. 2014

Neuropsychopharmacol

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Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus, and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes are found only in some studies of BD subjects and may thus be secondary to the presence of certain clinical variables. Studying BD patients with abnormal glucose metabolism could help identify preventable risk factors for hippocampal atrophy in BD. We compared brain structure using optimized voxel-based morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15 euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes than the euglycemic BD participants (corrected p ¼ 0.02) or euglycemic, nonpsychiatric controls (corrected p ¼ 0.004). Already the BD subjects with IR/GI had smaller hippocampal volumes than euglycemic BD participants (t(32) ¼ À 3.15, p ¼ 0.004). Age was significantly more negatively associated with hippocampal volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants (F(2, 44) ¼ 9.96, p ¼ 0.0003). The gray matter reductions in dysglycemic subjects extended to the cerebral cortex, including the insula. In conclusion, this is the first study demonstrating that T2DM or even prediabetes may be risk factors for smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may accelerate the age-related decline in hippocampal volumes in BD. These findings raise the possibility that improving diabetes care among BD subjects and intervening already at the level of prediabetes could slow brain aging in BD.

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Section: Discussionmentioning

confidence: 99%

Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

Hájek

Calkin

Blagdon

et al. 2014

Neuropsychopharmacol

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“…Although to date, we have conducted the only one study in drug-naïve bipolar subjects, describing glucose abnormalities through an increased 2-h glucose load (23). Indeed, altered glucose homeostasis (insulin dysfunction) has been theorized as the reason of the increased amount of medical comorbidities found in bipolar disorder (24). …”

mentioning

confidence: 99%

The thrifty psychiatric phenotype

García-Rizo

Fernández-Egea

Bernardo

et al. 2014

Acta Psychiatr Scand

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“…As allostatic load accumulates and attempts to maintain cellular homeostasis fail, cell danger signals are propagated and pro-apoptotic cell signaling pathways become increasingly engaged (36–39). This may play a role in medical comorbidities such as heart disease (40), as well as interfere with the therapeutic mechanisms of antidepressants and mood stabilizers to impair treatment efficacy (41–43).…”

Section: Biomarker Strategies For Prodromal Mood Disordersmentioning

confidence: 99%

Stress, Inflammation, and Cellular Vulnerability during Early Stages of Affective Disorders: Biomarker Strategies and Opportunities for Prevention and Intervention

et al. 2014

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The mood disorder prodrome is conceptualized as a symptomatic, but not yet clinically diagnosable stage of an affective disorder. Although a growing area, more focused research is needed in the pediatric population to better characterize psychopathological symptoms and biological markers that can reliably identify this very early stage in the evolution of mood disorder pathology. Such information will facilitate early prevention and intervention, which has the potential to affect a person’s disease course. This review focuses on the prodromal characteristics, risk factors, and neurobiological mechanisms of mood disorders. In particular, we consider the influence of early-life stress, inflammation, and allostatic load in mediating neural mechanisms of neuroprogression. These inherently modifiable factors have known neuroadaptive and neurodegenerative implications, and consequently may provide useful biomarker targets. Identification of these factors early in the course of the disease will accordingly allow for the introduction of early interventions which augment an individual’s capacity for psychological resilience through maintenance of synaptic integrity and cellular resilience. A targeted and complementary approach to boosting both psychological and physiological resilience simultaneously during the prodromal stage of mood disorder pathology has the greatest promise for optimizing the neurodevelopmental potential of those individuals at risk of disabling mood disorders.

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Insulin dysfunction and allostatic load in bipolar disorder

Cited by 55 publications

References 141 publications

Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

The thrifty psychiatric phenotype

Stress, Inflammation, and Cellular Vulnerability during Early Stages of Affective Disorders: Biomarker Strategies and Opportunities for Prevention and Intervention

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