Interleukin-1β Serum Levels is Increased in Antidepressant-Free Elderly Depressed Patients

doi:10.1097/JGP.0b013e3181c2947f

The American Journal of Geriatric Psychiatry

Volume 18, Issue 2, February 2010, Pages 172-176

https://doi.org/10.1097/JGP.0b013e3181c2947f Get rights and content

Objective

To assess the serum levels of interleukin 1β (IL-1β) in elderly depressed patients in comparison with nondepressed healthy elderly subjects.

Design

Cross-sectional study.

Setting

Tertiary memory clinic.

Participants

Twenty-three antidepressant-free elderly depressed patients and 44 nondepressed healthy elderly comparison group were enrolled to this study.

Measurement

Serum IL-1β levels were determined with highly sensitive colorimetric sandwich enzyme-linked immunosorbent assay. Severity of the depressive episode was determined by scores on the Hamilton Depression Scale-21 item and cognitive performance by the scores on the Cambridge Cognition Examination, Mini Mental State Examination clock drawing test, and verbal fluency.

Results

IL-1β serum levels were increased in elderly patients versus nondepressed elderly (t = 2.21, df = 65, p = 0.04). After categorizing elderly depressed subjects into late onset (LOD) versus early onset (EOD), patients with EOD had the highest IL-1β levels, when compared with nondepressed elderly patients and patients with LOD in analysis of variance (F = 4.9, df = 2, 64, p <0.01).

Conclusions

Late-life depression is associated with higher IL-1β levels suggesting that increased proinflammatory state may play a role in the physiopathology of depression in the elderly. The authors further show that this might be more prominent in those patients with EOD geriatric depression.

Section snippets

Subjects

Twenty-three elderly outpatients with current major depressive episode (first or recurrent episode) were recruited to this study. All patients underwent a comprehensive clinical, psychiatric, and cognitive assessment. The diagnosis of major depressive disorder was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria¹⁶ following the Structured Clinical Interview for DSM-IV disorders (Structured Clinical Interview for DSM-III-R).¹⁷ The

RESULTS

The sample comprised 23 elderly depressed outpatients (11 EOD and 12 LOD) and 44 nondepressed elderly subjects. No significant differences were found for the distribution of patients and nondepressed subjects for age and gender. Depressed patients had significantly worse cognitive performance, when compared with nondepressed subjects (Table 1).

IL-1β plasma levels were significantly higher in depressed patients (mean ± standard deviation, 7.8 ± 12.6 pg/mL) than in nondepressed subjects (mean ±

DISCUSSION

In this study, we found that serum IL-1β levels were elevated in elderly depressed patients. Interestingly, patients with EOD, i.e., patients with history of recurrent depressive disorder and age of the first episode before 60 years, had the highest IL-1β levels but not significantly different from LOD. A significant amount of experimental evidence from animals and human studies implicates the abnormal inflammatory response in the pathogenesis of sickness behavior, a condition that has

References (25)

CB Nemeroff
The curiously strong relationship between cardiovascular disease and depression in the elderly
Am J Geriatr Psychiatry
(2008)
MA Rapp et al.
Depression predicts mortality in the young old, but not in the oldest old: results from the Berlin Aging study
Am J Geriatr Psychiatry
(2008)
NM Simon et al.
A detailed examination of cytokine abnormalities in major depressive disorder
Eur Neuropsychopharmacol
(2008)
L Capuron et al.
Cytokines and psychopathology: lessons from interferon-α
Biol Psychiatry
(2004)
MA Bremmer et al.
Inflammatory markers in late-life depression: results from a population-based study
J Affect Disord
(2008)
BW Penninx et al.
Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition study
Biol Psychiatry
(2003)
R Dantzer et al.
Twenty years of research on cytokine-induced sickness behavior
Brain Behav Immun
(2007)
TJ Story et al.
Neurocognitive correlates of response to treatment in late-life depression
Am J Geriatr Psychiatry
(2008)
BT Baune et al.
Association between genetic variants of IL-1beta, Ill-6 and TNF-alpha cytokines and cognitive performance in the elderly general population of the MEMO-study
Psychoneuroendocrinology
(2008)
MF Folstein et al.
“Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975)

AH van den Biggelaar et al.

Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age

Exp Gerontol

(2007)

F Kapczinski et al.

Allostatic load in bipolar disorder: implications for pathophysiology and treatment

Neurosci Biobehav Rev

(2008)

Cited by (65)

Affective neural circuits and inflammatory markers linked to depression and anxiety symptoms in patients with comorbid obesity
2023, Journal of Psychiatric Research
Although we have effective treatments for depression and anxiety, we lack mechanistic understanding or evidence-based strategies to tailor these treatments in the context of major comorbidities such as obesity. The current feasibility study uses functional neuroimaging and biospecimen data to determine if changes in inflammatory markers, fecal short-chain fatty acids, and neural circuit-based targets can predict depression and anxiety outcomes among participants with comorbid obesity. Blood and stool samples and functional magnetic resonance imaging data were obtained at baseline and 2 months, during the parent ENGAGE-2 trial. From 30 participants with both biospecimen and fMRI data, this subsample study explored the relationship among changes in inflammatory markers and fecal short-chain fatty acids and changes in neural targets, and their joint relationship with depression and anxiety symptoms. Bivariate and partial correlation, canonical correlation, and partial least squares analyses were conducted, with adjustments for age, sex, and treatment group. Initial correlation analyses revealed three inflammatory markers (IL-1RA, IL-6, and TNF-α) and five neural targets (in Negative Affect, Positive Affect, and Default Mode Circuits) with significantly associated changes at 2 months. Partial least squares analyses then showed that changes in IL-1RA and TNF-α and changes in three neural targets (in Negative Affect and Positive Affect Circuits) at 2 months were associated with changes in depression and anxiety symptoms at 6 months. This study sheds light on the plausibility of incorporation of inflammatory and gastrointestinal biomarkers with neural targets as predictors of depression and comorbid anxiety outcomes among patients with obesity.
The NLRP3 inflammasome in depression: Potential mechanisms and therapies
2023, Pharmacological Research
Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression.
Depression duration and risk of incident cardiovascular disease: A population-based six-year cohort study
2022, Journal of Affective Disorders
Depression symptoms are significantly associated with an increased risk of cardiovascular disease (CVD). However, understanding of the magnitude of the association between depression duration and risk of CVD is limited. Therefore, we aimed to assess whether a longer duration of exposure to depression is associated with a higher risk of new-onset CVD.
We conducted a territory-wide retrospective cohort study among patients (≥ 10 years old) with depression diagnosed between January and December 2014 in Hong Kong. The observation period spanned January 1, 2014, to December 31, 2019, and all participants had no CVD at baseline. Incidence of CVD was calculated. We used Cox proportional hazard regression to adjust confounders and estimate hazard ratios of CVD risk.
Among 11,651 participants with depression, 1306 (11.2%) individuals developed CVD. Multi-adjusted models showed individuals with depression duration of 2–5 years (Hazard Ratios [HRs]: 1.38 [95% confidence interval (CI): 1.19–1.60]) and ≥6 years (1.45 [1.25–1.68]) had a significantly escalated risk of developing CVD, compared to those with depression within one year. Stratified analyses indicated that the association was prominent in women and those under 65 years old.
Lack of depression severity information and the small sample size in some subgroup analyses.
Longer exposure to depression is associated with significant increased risk of CVD. The interplay between mental and vascular health emphasizes the need for CVD prevention in patients with long-term depression.
Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls
2020, Brain, Behavior, and Immunity
The magnitude and variability of cytokine alterations in depression are not clear.
To perform an up to date meta-analysis of mean differences of immune markers in depression, and to quantify and test for evidence of heterogeneity in immune markers in depression by conducting a meta-analysis of variability to ascertain whether only a sub-group of patients with depression show evidence of inflammation.
Studies that reported immune marker levels in peripheral blood in patients with depression and matched healthy controls in the MEDLINE database from inception to August 29th 2018 were examined.
Case-control studies that reported immune marker levels in peripheral blood in patients with depression and healthy controls were selected.
Means and variances (SDs) were extracted for each measure to calculate effect sizes, which were combined using multivariate meta-analysis.
Hedges g was used to quantify mean differences. Relative variability of immune marker measurements in patients compared with control groups as indexed by the coefficient of variation ratio (CVR).
A total of 107 studies that reported measurements from 5,166 patients with depression and 5,083 controls were included in the analyses. Levels of CRP (g = 0.71; 95%CI: 0.50–0.92; p < 0.0001); IL-3 (g = 0.60; 95%CI: 0.31–0.89; p < 0.0001); IL-6 (g = 0.61; 95%CI: 0.39–0.82; p < 0.0001); IL-12 (g = 1.18; 95%CI: 0.74–1.62; p < 0.0001); IL-18 (g = 1.97; 95%CI: 1.00–2.95; p < 0.0001); sIL-2R (g = 0.71; 95%CI: 0.44–0.98; p < 0.0001); and TNFα (g = 0.54; 95%CI: 0.32–0.76; p < 0.0001) were significantly higher in patients with depression. These findings were robust to a range of potential confounds and moderators. Mean-scaled variability, measured as CVR, was significantly lower in patients with depression for CRP (CVR = 0.85; 95%CI: 0.75–0.98; p = 0.02); IL-12 (CVR = 0.61; 95%CI: 0.46–0.80; p < 0.01); and sIL-2R (CVR = 0.85; 95%CI: 0.73–0.99; p = 0.04), while it was unchanged for IL-3, IL-6, IL-18, and TNF α.
Depression is confirmed as a pro-inflammatory state. Some of the inflammatory markers elevated in depression, including CRP and IL-12, show reduced variability in patients with depression, therefore supporting greater homogeneity in terms of an inflammatory phenotype in depression. Some inflammatory marker elevations in depression do not appear due to an inflamed sub-group, but rather to a right shift of the immune marker distribution.
Neuroinflammation and depressive disorder: The role of the hypothalamus
2020, Journal of Clinical Neuroscience
Data accumulated over the last two decades has demonstrated that hypothalamic inflammation plays an important role in the etiopathogenesis of the most prevalent diseases, such as cardiovascular diseases, metabolic syndrome, and even cancer. Recent findings indicate that hypothalamic inflammation is also associated with stress exposure and certain psychiatric diseases, such as depressive disorder. Mechanistic studies have shown that intense and/or chronic stress exposure is accompanied by the synthesis of inflammatory molecules in the hypothalamus, altered hypothalamic–pituitary-adrenal axis activity, and development of glucocorticoid resistance. Consequently, these factors might play a role in the etiopathogenesis of psychiatric disorders. We propose that hypothalamic inflammation represents an interconnection between somatic diseases and depressive disorder. These assumptions are discussed in this mini-review in the light of available data from studies focusing on hypothalamic inflammation.
Biomarkers of cognitive impairment in late-life depression
2020, Handbook of Mental Health and Aging
Late-life depression is one of the most common neuropsychiatric disorders in older adults. In community-dwelling older adults, the prevalence of major depression ranges from 4% to 22% and the prevalence of clinically significant depressive symptoms (i.e., the presence of depressive symptoms that do not fulfill diagnostic criteria for a major depressive episode) is even higher, ranging from 20% to 40%.

View all citing articles on Scopus

: This work was supported by grants from Rede Instituto Brasileiro de Neurociência (IBN Net/Finep), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant no. 02/12633-7), Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS), and CAPES, Brazil (to BSD).

View full text

Regular Research ArticlesInterleukin-1β Serum Levels is Increased in Antidepressant-Free Elderly Depressed Patients

Objective

Design

Setting

Participants

Measurement

Results

Conclusions

Section snippets

Subjects

RESULTS

DISCUSSION

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Eur Neuropsychopharmacol

Biol Psychiatry

J Affect Disord

Biol Psychiatry

Brain Behav Immun

Am J Geriatr Psychiatry

Psychoneuroendocrinology

J Psychiatr Res

Exp Gerontol

Neurosci Biobehav Rev

Regular Research Articles
Interleukin-1β Serum Levels is Increased in Antidepressant-Free Elderly Depressed Patients