Increased Proinflammatory Cytokines, Executive Dysfunction, and Reduced Gray Matter Volumes In First-Episode Bipolar Disorder and Major Depressive Disorder

Chen, Mu Hong; Kao, Zih-Kai; Chang, Wan Chen; Tu, Pei Chi; Hsu, Ju Wei; Huang, Kou‐Yuan; Su, Tung Ping; Li, Cheng Ta; Lin, Wei Chen; Tsai, Shih Jen; Bai, Ya Mei

doi:10.1016/j.jad.2020.05.158

Cited by 54 publications

(29 citation statements)

References 43 publications

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“…The MFG, a vital component of the dorsal lateral prefrontal cortex (DLPFC), is involved in attention (60), cognitive control functions (61), and working memory (62). Our study replicates previous results showing that greater gray matter volumes in the MFG were related to better executive function (63). A study by Cui et al identified the phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a gene related to thyroid function, was associated with pathological and physiological changes in MDD (64).…”

Section: Relationships Between Thyroid Function Frontal Gray Matter and Executive Functionsupporting

confidence: 87%

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder

et al. 2021

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The present study was aimed to investigate the relationships between serum thyroid hormones (THs), frontal gray matter volume, and executive function in selected patients with major depressive disorder (MDD). One hundred and four MDD patients and seventy-five healthy controls (HCs) were subjected to thyroid-stimulating hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), and executive function tests and underwent structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis was performed to compare group differences in the gray matter for the frontal lobe. Furthermore, mediation analysis was used to investigate whether gray matter volumes of the frontal gyrus mediated the relationship between serum THs and executive function in MDD patients. MDD patients exhibited significant gray matter volume reduction in several brain regions, including the left rectus, right middle frontal cortex, and left middle frontal cortex. Serum TSH levels are positively associated with altered regional gray matter volume patterns within MFG and executive function. Importantly, gray matter in the right MFG was a significant mediator between serum TSH levels and executive function. These findings expand our understanding of how thyroid function affects brain structure changes and executive function in MDD patients.

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Section: Relationships Between Thyroid Function Frontal Gray Matter and Executive Functionsupporting

confidence: 87%

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder

et al. 2021

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“…Additionally, chronic proinflammatory and oxidative processes have been identified to be involved in the degeneration of the central nervous system in BD, such as neural activity and brain structure, which in turn is related to cognitive decline ( Anderson and Maes, 2015 ). These mechanisms impair especially executive function ( Tseng et al, 2021 ), and additionally, a link to reduced frontal cortex volume was found ( Chen et al, 2020 ). Interestingly, the inflammatory process of MetS is suspected to share a common biological pathway with BD: the kynurenine pathway, which stimulates the production of neurotoxic metabolites as a response to stress, thus contributing to endothelial dysfunction ( Halaris, 2017 ; Benedetti et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome Impairs Executive Function in Bipolar Disorder

et al. 2021

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Background: Metabolic syndrome (MetS) is more prevalent in individuals with bipolar disorder and has a negative impact on cognition, in particular on executive function, which is already impaired in individuals with bipolar disorder compared to healthy controls.Methods: In a cross-sectional study, we compared 148 euthymic patients with bipolar disorder and 117 healthy controls in cognitive function depending on the diagnosis of MetS. A neuropsychological test battery was used including the Trail Making Test A/B, Stroop Color and Word Interference Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. In addition, MetS variables as well as the defining variables waist circumference, serum triglyceride levels, high-density lipoprotein cholesterol levels, blood pressure, fasting glucose levels, and body mass index were compared between patients and controls. In addition, illness-related variables were associated with MetS in individuals with bipolar disorder.Results: The prevalence of MetS in patients with bipolar disorder was higher than in controls (30.4 vs. 15.4%). Patients with bipolar disorder with MetS had impaired executive function compared to patients without MetS or healthy controls with and without MetS (p = 0.020). No MetS effects or interaction MetS × Group was found in attention/processing speed (p = 0.883) and verbal learning/memory (p = 0.373). Clinical variables (illness duration, suicidality, number of affective episodes, medication, age of onset, and history of psychosis) did not relate to MetS in bipolar disorder (p > 0.05).Conclusion: Bipolar disorder comorbid with MetS bears additional risk for impaired executive function. Executive function includes action planning, inhibition, and impulse control and could play a critical role in keeping long-term goals in mind associated with gaining and maintaining a healthy weight.

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“…Those authors additionally observed that the level of eotaxin was negatively correlated with executive function (set-shifting performance) as measured by the Trail-Making Test. 111 Another structural MRI study (by Chen et al 112 ) investigated 44 patients with mood disorders (22 with MDD and 22 with bipolar disorder) and 22 healthy controls, and found that the serum level of TNF-α receptor-1 was positively correlated with the gray-matter volume of the left middle frontal cortex, which was positively correlated with executive function as measured by the Wisconsin Card Sorting Test in the entire sample. Similar to the aforementioned two studies, a study involving a larger sample of the nonpsychiatric population found significant correlations between several peripheral markers and the gray-matter volume.…”

Section: Peripheral Inflammatory Markers and Depression: Structural Neuroimaging Findingsmentioning

confidence: 99%

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

Han

Ham

2021

J Clin Neurol

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This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamate-mediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depression-related neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

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Increased Proinflammatory Cytokines, Executive Dysfunction, and Reduced Gray Matter Volumes In First-Episode Bipolar Disorder and Major Depressive Disorder

Cited by 54 publications

References 43 publications

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder

Metabolic Syndrome Impairs Executive Function in Bipolar Disorder

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies

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