Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: the role of cognitive-affective and somatic symptoms.
ABSTRACT: Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity and inflammation are thought to be prominent in the aetiology of depression. Although meta-analyses have confirmed this relationship, there is considerable variability in the effect sizes across studies. This could be attributed to a differential role of such biological systems in somatic versus cognitive-affective depressive symptoms which remains largely unexplored. Furthermore, most longitudinal research to date has focused on transient rather than persistent depressive symptoms. In the current study, we investigated the associations of hair cortisol and plasma C-reactive protein (CRP) with the longitudinal persistence and dimensions (cognitive-affective versus somatic) of depressive symptoms over a 14-year period using Trait-State-Occasion (TSO) structural equation modelling. The data came from a large sample of older adults from the English Longitudinal Study of Ageing. Depressive symptoms were assessed from wave 1 (2002-03) to wave 8 (2016-17). Hair cortisol (N?=?4761) and plasma CRP (N?=?5784) were measured in wave 6 (2012-13). Covariates included demographic, socioeconomic, lifestyle, chronic disease, and medication data. Our results revealed that higher cortisol and CRP levels were significantly associated with persistent depressive symptoms across the study period. Notably, both biomarkers exhibited stronger relationships with somatic than with cognitive-affective symptoms. The associations with somatic symptoms were also independent of relevant confounding factors. In contrast, their associations with cognitive-affective symptoms were weak after adjustment for all covariates. These distinct associations reveal the importance of considering symptom-specific effects in future studies on pathophysiological mechanisms. Ultimately, this will have the potential to advance the search for biomarkers of depression and facilitate more targeted treatments.
Project description:Genetic susceptibility to depression has been established using polygenic scores, but the underlying mechanisms and the potentially differential effects of polygenic scores on specific types of depressive symptoms remain unknown. This study examined whether systemic low-grade inflammation mediated the association between polygenic scores for depressive symptomatology (DS-PGS) and subsequent somatic versus cognitive-affective depressive symptoms. The sample consisted of 3510 men and women (aged 50+) recruited from the English Longitudinal Study of Ageing. DS-PGS were derived using the results of a recent genome-wide association study. Plasma C-reactive protein (CRP) was measured at wave 6 (2012/13). Depressive symptoms were assessed at wave 8 (2016/17), using the eight-item version of the Centre for Epidemiological Studies Depression Scale. Covariates (wave 2, 2004/05) included age, sex and ten principal components (PCs) to control for population stratification. Confirmatory factor analysis was performed to corroborate a previously identified two-factor structure of the CES-D, distinguishing between cognitive-affective and somatic symptoms. Longitudinal structural equation modelling was used to investigate the mediating role of CRP in the relationship between DS-PGS and cognitive-affective versus somatic symptoms. Our results showed that participants with a higher polygenic susceptibility to DS were significantly more likely to report cognitive-affective and somatic symptoms at follow-up. Mediation analyses revealed that CRP mediated the relationship between DS-PGS and somatic symptoms, but not the association between DS-PGS and cognitive-affective symptoms. These differential effects highlight the importance of considering individual differences in depression profiles in future studies. Ultimately, this will inform healthcare professionals to design more targeted treatments.
Project description:Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals particularly vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms.Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions.There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001).The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment.BDNF genotype is an indirect measure of BDNF protein levels.
Project description:Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes' difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N=102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients' lives and thus warrant further assessment and treatment.
Project description:Depression is an independent predictor of adverse outcomes in patients with heart failure (HF). However, the effect of changes in cognitive-affective and somatic symptoms on mortality of HF patients is not known. The purpose of this study was to examine whether changes in cognitive-affective and somatic depressive symptoms over time were associated with mortality in HF.In this secondary analysis of data from the Rural Education to Improve Outcomes in Heart Failure clinical trial, we analyzed data from 457 HF patients (39% female, mean [standard deviation] age = 65.6 [12.8] years) who survived at least 1 year and repeated the Patient Health Questionnaire at 1 year. Cognitive-affective and somatic depression scores were calculated, respectively, based on published Patient Health Questionnaire factor models. Using Cox proportional hazards regression analyses, we evaluated the effect of changes in cognitive-affective and somatic symptoms from baseline to 1 year on cardiac and all-cause deaths.Controlling for baseline depression scores and other patient characteristics, the change in somatic symptoms was associated with increased risk of cardiac death during the subsequent 1-year period (hazard ratio = 1.24, 95% confidence interval = 1.07-1.44, p = .005), but the change in cognitive-affective symptoms was not (hazard ratio = 0.94, 95% confidence interval = 0.81-1.08, p = .38). Similar results were found for all-cause mortality.Worsening somatic depressive symptoms, not cognitive-affective symptoms, are independently associated with increased mortality of HF patients. The findings suggest that routine and ongoing assessment of somatic depressive symptoms in HF patients may help clinicians identify patients at increased risk for adverse outcomes.ClinicalTrials.gov NCT00415545.
Project description:AIMS:The objective of this study is to investigate whether type of depressive symptoms (i.e. cognitive-affective or somatic) is related to a patient-perceived need for professional psychological care in individuals with diabetes. METHODS:In total 2266 participants were recruited as part of the screening procedure for a multi-center randomized controlled trial on the treatment of depressive symptoms among individuals with diabetes. Individuals were invited to complete Beck Depression Inventory-II (BDI-II). Patients with elevated depressive symptoms (BDI-II ?14) were interviewed about their psychological care need. Based on their care needs patients were categorized into: unmet need, no need, met need and unclear need. These groups were compared on type of depressive symptoms, as categorized into cognitive-affective symptoms and somatic symptoms. RESULTS:568 eligible individuals had elevated depressive symptoms, of whom 519 were reached. Among these depressed individuals, 19.7% (102 of 519) had an unmet need for psychological care. Participants with an unmet need were younger (p<0.001) and had higher total depression scores compared to the group with no need (p<0.001). They also scored higher on cognitive-affective symptoms (p<0.001), whereas somatic symptoms did not significantly differ (p = 0.232). Logistic regression revealed that cognitive-affective symptoms predicted an unmet need (p = 0.001). However, overall predictive capacity of type of depressive symptoms on care needs was weak. CONCLUSIONS:Cognitive-affective symptoms of depression-but not somatic symptoms-were associated with an unmet need for psychological care among depressed individuals with diabetes. Future research is needed to reveal better predictors explaining the discrepancy between distress and low care needs in order to optimize screening procedures.
Project description:This study evaluated the distinctive clinical and biological manifestations of depressive symptom subtypes (i.e., cognitive-affective and somatic) in Veterans with hepatitis C viral infection (HCV) before and during interferon-alpha (IFN) based antiviral therapy.Thirty-two Veterans with HCV and no prior history of IFN therapy were followed prospectively during the first 16weeks of therapy to evaluate depressive symptoms and to determine if baseline cytokine and serotonin levels predicted subsequent changes in depressive scores.IFN therapy resulted in a significant increase in total depressive symptoms from baseline (week 0) to week 16, with neurovegetative and somatic symptoms of depression including loss of appetite, fatigue and irritability increasing within the first two weeks of therapy and continuing to increase throughout IFN therapy. When depressive symptoms were evaluated using a two-factor (i.e., Cognitive-Affective and Somatic) model, the Cognitive-Affective factor score did not change significantly following IFN therapy initiation, while the Somatic factor score showed a significant increase from week 0 to week 16. Veterans with the largest increases in somatic symptoms from week 0 to week 2 had significantly higher levels of tumor necrosis factor-alpha (TNF-?) and lower levels of serotonin at baseline, as compared to Veterans with minimal or no increase in somatic symptoms.Somatic symptoms of depression can be significantly exacerbated during IFN therapy and may be predicted by higher TNF-? levels and lower serotonin levels at baseline.
Project description:To examine longitudinal bidirectional associations between two depressive symptom clusters-the cognitive-affective and somatic-vegetative clusters--and insulin resistance, a marker of prediabetes.Participants were 269 adults aged 50 to 70 years without diabetes enrolled in the Pittsburgh Healthy Heart Project, a prospective cohort study. At baseline and 6-year visits, participants completed the Beck Depression Inventory-II (BDI-II) and underwent a blood draw to quantify fasting insulin and glucose. We examined baseline BDI-II total, cognitive-affective, and somatic-vegetative scores as predictors of 6-year change in the homeostatic model of assessment (HOMA) score, an estimate of insulin resistance computed from fasting insulin and glucose. We also examined baseline HOMA score as a predictor of 6-year change in BDI-II total and subscale scores.Regression analyses, adjusted for demographic factors and baseline HOMA score, revealed that the baseline BDI-II somatic-vegetative score (? = 0.14, p = .025), but not the cognitive-affective (? = 0.001, p = .98) or total (? = 0.10, p = .11) scores, predicted 6-year HOMA change. This result persisted in models controlling for anxiety symptoms and hostility. Several factors were examined as candidate mediators; however, only change in body mass index was a significant mediator (p = .042), accounting for 23% of the observed association. Baseline HOMA score did not predict 6-year change in BDI-II total or subscale scores (all p values >.56).Among adults aged 50 to 70 years, the somatic-vegetative symptoms of depression (e.g., fatigue, sleep disturbance, and appetite changes) may worsen insulin resistance and increase diabetes risk, partly, by increasing body mass index.
Project description:Background/Objective: Almost no attention has been paid to depression in Friedreich ataxia (FRDA), a highly disabling cerebellar degenerative disease. Our aim was to study the presence and the profile of depressive symptoms in FRDA and their relationship with demographic-disease variables and cognitive processing speed. Method: The study groups consisted of 57 patients with a diagnosis of FRDA. The Beck Depression Inventory-II was used to assess symptoms of depression. Speed of information processing was measured with a Choice Reaction time task. Results: The mean BDI score for patients was significantly higher than the mean score in the general population. Twenty one percent of participants scored in the moderate/severe range. A Cognitive-Affective score and a Somatic-Motivational score was calculated for each patient. Patients' scores in both dimensions were significantly higher than the scores in the general population. Demographic and disease variables were not related with symptoms of depression, except for severity of ataxia. Depressive symptoms predict cognitive reaction times. The greater proportion of variance was explained by the Cognitive-Affective dimension. Conclusions: Our data show that both somatic-motivational and cognitive affective symptoms of depression are frequent in individuals with FRDA. In addition, depressive symptoms may influence cognition, especially, the cognitive and affective symptoms.
Project description:The hedonic view on well-being, consisting of both cognitive and affective aspects, assumes that through maximizing pleasurable experiences, and minimizing suffering, the highest levels of well-being can be achieved. The eudemonic approach departs from the concept of a good life that is not just about pleasure and happiness, but involves developing one-self, being autonomous and realizing one's potential. While these approaches are often positioned against each other on theoretical grounds, this paper investigates the empirical plausibility of this two dimensional view on subjective well-being. The interrelations between common measures such as the General Health Questionnaire, the CES-D inventory of depressive symptoms, the satisfaction with life scale and the eudemonic CASP scale are examined in a confirmatory factor analysis framework using the third wave of the English Longitudinal Study of Ageing (ELSA). A multidimensional structure of well-being, distinguishing cognitive, affective and eudemonic well-being, is shown to be the best fitting empirical solution. This three dimensional second order structure is neutral to gender in its measurement. A lower influence of feeling energetic on self-actualisation, and of somatic symptoms of depression on affective well-being was noted for respondents in the fourth age in comparison to respondents in the third age. These small measurement artefacts underline that somatic symptoms of later life depression should be distinguished from mood symptoms. Two main social facts are confirmed when we compare the different forms of well-being over gender and life stage: men tend to have a higher level of well-being than women, and well-being is lower in the fourth age than in the third age. Although the three measures are very closely related, with high correlations between .74 and .88, they each have their specific meaning. While affective and cognitive well-being emphasize the use of an internal yardstick to measure well-being, the eudemonic perspective adds an external dimension. As each measure has an own story to tell, we advocate the use of these multiple assessments of well-being.
Project description:Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR) and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.