Insulin resistance is associated with verbal memory impairment in bipolar disorders

Salvi, Virginio; Salvo, Gabriele Di; Korčáková, Jana; Torriero, Sara; Aragno, Elena; Kolenič, Marián; Ungrmanova, M.; Maina, Giuseppe; Mencacci, Claudio; Hájek, Tomáš

doi:10.1016/j.jad.2020.01.145

Cited by 13 publications

(14 citation statements)

References 40 publications

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“…Much less appreciated, but equally important, are the negative effects of these medical conditions on psychiatric and brain outcomes. Long before obesity contributes to premature mortality, it may worsen psychiatric prognosis, possibly through its impact on brain structure/cognitive functioning 7–11 …”

Section: Introductionmentioning

confidence: 99%

“…Long before obesity contributes to premature mortality, it may worsen psychiatric prognosis, possibly through its impact on brain structure/cognitive functioning. [7][8][9][10][11] Indeed, the brain is one of the targets for obesity-related endorgan damage, long before the development of cardiovascular complications. 12 Obesity is consistently associated with lower cortical thickness in large studies 13,14 and meta-analyses.…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness—ENIGMA study in 2436 individuals

et al. 2021

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Aims: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. Methods:We obtained body mass index (BMI) and magnetic resonance imagingderived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. Results:We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness—ENIGMA study in 2436 individuals

et al. 2021

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“…We have found that those with comorbid T2DM or IR were more likely to develop a chronic course of BD, more rapid cycling, and were less likely to respond to lithium compared to those without metabolic dysregulation ( 4 ). Similarly, poor outcomes in BD with comorbid IR have been reported, including worse cognitive decline ( 5 ), memory impairment ( 6 ), and poor response to mood stabilizers in general ( 7 ). Understanding mechanisms underlying these findings could lead to novel therapeutic or adjunctive treatment strategies.…”

Section: Introductionmentioning

confidence: 93%

Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder

et al. 2021

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Bipolar disorder (BD) often progresses to a more chronic and treatment resistant (neuroprogressive) course. Identifying which patients are at risk could allow for early intervention and prevention. Bipolar disorder is highly comorbid with metabolic disorders including type II diabetes mellitus (T2DM), hypertension, obesity, and dyslipidemia. Our studies have shown that insulin resistance (IR) is present in over 50% of patients with BD and that IR might underlie the progression of BD. While no confirmed predictors exist for identifying which patients with BD are likely to develop a more chronic course, emerging evidence including our own studies suggest that IR and related inflammatory pathways lead to impairments in blood-brain barrier (BBB) functioning. For the first time in living psychiatric patients, we have shown that the severity of BBB leakage is proportional to BD severity and is associated with IR. In this hypothesis paper we (i) highlight the evidence for a key role of IR in BD, (ii) show how IR in BD relates to shared inflammatory pathways, and (iii) hypothesize that these modulations result in BBB leakage and worse outcomes in BD. We further hypothesize that (iv) reversing IR through lifestyle changes or the actions of insulin sensitizing medications such as metformin, or optimizing BBB function using vascular protective drugs, such as losartan, could provide novel strategies for the prevention or treatment of neuroprogressive BD.

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“…The presence of MetS has implications for medical health and mortality, but it may also impact the clinical characteristics of the psychiatric disorder. Previous work has demonstrated that individuals with BD and MetS or its components have an increased severity of psychiatric symptoms, more lifetime episodes, more hospitalizations, shorter remissions, lower functioning, greater risk of disability, increased risk of suicide attempts, and impairments in cognitive functioning [3][4][5][6][7][8][9][10][11][12]. Additionally these individuals have poorer response to psychiatric medications [4,13].…”

Section: Introductionmentioning

confidence: 99%

Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers?

2022

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Insulin-sensitizing medications were originally used in psychiatric practice to treat weight gain and other metabolic side effects that accompany the use of mood stabilizers, antipsychotics, and some antidepressants. However, in recent studies these medications have been shown to cause improvement in depressive symptoms, creating a potential new indication outside of metabolic regulation. However, it is still unclear whether the antidepressant properties of these medications are associated with improvements in metabolic markers. We performed a systematic search of the literature following PRISMA guidelines of studies investigating antidepressant effects of insulin-sensitizing medications. We specifically focused on whether any improvements in depressive symptoms were connected to the improvement of metabolic dysfunction. Majority of the studies included in this review reported significant improvement in depressive symptoms following treatment with insulin-sensitizing medications. Nine out of the fifteen included studies assessed for a correlation between improvement in symptoms and changes in metabolic markers and only two of the nine studies found such association, with effect sizes ranging from R2 = 0.26–0.38. The metabolic variables, which correlated with improvements in depressive symptoms included oral glucose tolerance test, fasting plasma glucose and glycosylated hemoglobin following treatment with pioglitazone or metformin. The use of insulin-sensitizing medications has a clear positive impact on depressive symptoms. However, it seems that the symptom improvement may be unrelated to improvement in metabolic markers or weight. It is unclear which additional mechanisms play a role in the observed clinical improvement. Some alternative options include inflammatory, neuroinflammatory changes, improvements in cognitive functioning or brain structure. Future studies of insulin-sensitizing medications should measure metabolic markers and study the links between changes in metabolic markers and changes in depression. Additionally, it is important to use novel outcomes in these studies, such as changes in cognitive functioning and to investigate not only acute, but also prophylactic treatment effects.

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Insulin resistance is associated with verbal memory impairment in bipolar disorders

Cited by 13 publications

References 40 publications

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness—ENIGMA study in 2436 individuals

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness—ENIGMA study in 2436 individuals

Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder

Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers?

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