Immunological biomarkers associated with brain structure and executive function in late‐life depression: exploratory pilot study

Smagula, Stephen F.; Lotrich, Francis E.; Aizenstein, Howard; Diniz, Breno S.; Krystek, Jeffrey R.; Wu, Gregory F.; Mulsant, Benoit H.; Butters, Meryl A.; Reynolds, Charles F.; Lenze, Eric J.

doi:10.1002/gps.4512

Cited by 34 publications

(17 citation statements)

References 52 publications

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“…Nota et al found elevated systemic TNF-α and IL-4 levels in patients with first episode psychosis and depressive symptoms, compared to non-depressed psychotic patients (102). Smagula et al found peripheral inflammatory biomarkers, including TNF-α levels to be associated with brain structure in patients with late-life depression (103). Depressive symptoms and accompanying inflammation may characterize a subset of schizophrenia patients with somewhat distinct pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables

Lee

Hong

Martin

et al. 2017

The American Journal of Geriatric Psychiatry

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Objective Inflammation may play a role in the accelerated physical aging reported in schizophrenia though biomarker findings and associations with demographic and clinical factors are inconsistent. Design Cross-sectional, case-control design Setting Community-dwelling participants tested in an academic laboratory. Participants 95 outpatients with schizophrenia (mean age ± SD: 48.1 ± 10.2 yrs) and 95 demographically-comparable healthy comparison subjects (HCs) (mean age ± SD: 48.1 ± 12.1 yrs) Measurements Sociodemographic and clinical data were collected, and plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ) were assayed. We compared cytokine levels, examined demographic and clinical associations. and adjusted for relevant variables with linear models. Results Individuals with schizophrenia had higher levels of TNF-α and IL-6, but not IFN-γ, than HCs. Age was not related to cytokine levels, and age relationships did not differ between diagnostic groups. Women had higher levels of IL-6. TNF-α and IL-6 levels were significantly correlated with depressive symptoms, and adjustment for depression reduced the group effect for both. Within the HCs, TNF-α levels were associated with physical comorbidity and body mass index (BMI). IL-6 levels were significantly correlated with BMI, and within schizophrenia patients, with worse mental and physical well-being. Accounting for physical morbidity and mental well-being reduced group differences in TNF-α and IL-6 levels, respectively. Worse positive symptoms were associated with higher IL-6 levels. Conclusions Higher TNF-α and IL-6 levels in schizophrenia patients were associated with depression, physical comorbidity, and mental well-being. Further longitudinal studies are warranted to assess inflammation as a potential treatment target for a subgroup of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables

Lee

Hong

Martin

et al. 2017

The American Journal of Geriatric Psychiatry

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“…Overall, these findings suggest that mechanisms underlying depression in T2D might originate from neurobiological substrates other than cerebrovascular risks/diseases [ 42–45 ], or be linked to cerebrovascular disease [ 46 ] such as brain atrophy, interleukins, and cortisol levels. In the general elderly population with major depressive disorder, Smagula and colleagues reported significant findings from pilot data on the associations among immunological markers, brain structure, and executive function [ 47 ]. Similarly, Charlton and colleagues reported an association between pro-inflammatory cytokines and memory function in late-life depression [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Depressive Symptoms Are Associated with Cognitive Function in the Elderly with Type 2 Diabetes

Guerrero‐Berroa

Ravona‐Springer

Schmeidler

et al. 2018

JAD

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Background:Type 2 diabetes (T2D) is a metabolic condition associated with poor clinical and cognitive outcomes including vascular disease, depressive symptoms, cognitive impairment, and dementia. In the general elderly population, depression has been consistently identified as a risk factor for cognitive impairment/decline. However, the association between depression and cognitive function in T2D has been understudied.Objective:We investigated the association between depression and cognitive function in a large sample of cognitively normal elderly with T2D.Methods:In this cross-sectional study, we examined 738 participants, aged 65–88 years old, enrolled in the Israel Diabetes and Cognitive Decline study. For each cognitive domain (Episodic Memory, Executive Function, Attention/Working Memory, Language/Semantic Categorization) and Overall Cognition, multiple linear regressions assessed its association with depression (score greater than 5 on the 15-item version of the Geriatric Depression Scale [GDS]), adjusting for age, sex, and education.Results:Depression (n = 66, 8.9%) was associated with worse performance on tasks of Executive Function (p = 0.004), Language/Semantic Categorization (p < 0.001), and Overall Cognition (p < 0.002), but not Episodic Memory (p = 0.643) or Attention/Working Memory (p = 0.488). Secondary analyses using GDS as a continuous variable did not substantially change the results. Adjusting also for a history of antidepressant medication use slightly weakened the findings.Conclusion:Significant associations of depression with several cognitive domains and Overall Cognition even in cognitively normal elderly with T2D, suggest that depression may have a role in impaired cognitive function in T2D, which may be attenuated by antidepressants.

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“…5 Moreover, Smagula, and his team's work found that tumor necrosis factor alpha (TNF-α) had a significant positive relationship with white matter hyperintensity volume, linking immunological markers with brain structure in late-life MDD patients. 6 In addition, recent data suggested that neuroinflammation played an important role in normal brain functions as well as in pathological brain processes, 7 and it acts in pathogenesis of depression. 8 The evidence showed that high mobility group protein box 1 (HMGB1) could promote neuroregeneration 9 and trigger neuroinflammtion.…”

Section: Introductionmentioning

confidence: 99%

The role of HMGB1 in neuroinflammation and tissue repair: A potential therapeutic target for depression?

Liu

Zhao

et al. 2018

Tradit. Med. Mod. Med.

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High mobility group protein box 1 (HMGB1), a sophisticated danger signal with pleiotropic functions, has been proved to function as a pro-inflammatory cytokine. In the central neural system (CNS), HMGB1 can stimulate microglia, the immune cell in the CNS, to release inflammatory factors and to cause chronic neurodegeneration. The evidence showed that HMGB1 can act as a pro-inflammatory cytokine mainly through its receptors like advanced glycation end product (RAGE), Toll-like 4 (TLR4), and so on. Moreover, HMGB1 contributed to the priming effects of stress-pretreatment and played a key role in neurodegeneration diseases via mediating neuroinflammation. However, the evidence also showed that HMGB1 played a role in tissue repair, with the ability to promote cell migration and proliferation, to induce the differentiation of mesenchymal stem cells (MSCs), and to regenerate spinal cord. These pleiotropic functions of HMGB1 make it possible to play a role from cell death to new life. Depression is a chronic, severe, and often life-threatening disease accompanied with impaired neurogenesis. The evidence showed that neuroinflammation played a key role in the process of depression. Depressive patients often showed a high expression of inflammatory cytokines in the blood and an activation of microglia in the brain. Meanwhile, they also showed a neuron deficit in the brain. Though they lack direct evidence linking HMGB1 with depression, the ability of HMGB1 that can function from neuroinflammation to tissue repair makes HMGB1 a promising therapeutic target of depression.

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Immunological biomarkers associated with brain structure and executive function in late‐life depression: exploratory pilot study

Cited by 34 publications

References 52 publications

Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables

Inflammation in Schizophrenia: Cytokine Levels and Their Relationships to Demographic and Clinical Variables

Depressive Symptoms Are Associated with Cognitive Function in the Elderly with Type 2 Diabetes

The role of HMGB1 in neuroinflammation and tissue repair: A potential therapeutic target for depression?

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