A systematic review and meta-analysis of the evidence on inflammation in depressive illness and symptoms in chronic and end-stage kidney disease.

BACKGROUND: Depression affects approximately 27% of adults with chronic kidney disease (CKD) and end-stage kidney failure (ESKF). Depression in this population is associated with impaired quality of life and increased mortality. The extent of inflammation and the impact on depression in CKD/ESKF is yet to be established. Through a systematic literature review and meta-analysis, we aim to understand the relationship between depression and inflammation in CKD/ESKF patients. METHODS: We searched nine electronic databases for published studies until January 2022. Titles and abstracts were screened against inclusion and exclusion criteria. Data extraction and study quality assessment was carried out independently by two reviewers. A meta-analysis was carried out where appropriate; otherwise a narrative review of studies was completed. RESULTS: Sixty studies met our inclusion criteria and entered the review (9481 patients included in meta-analysis). Meta-analysis of cross-sectional associations revealed significantly higher levels of pro-inflammatory biomarkers; C-reactive protein; Interleukin 6 (IL-6) and tumour necrosis factor-alpha in patients with depressive symptoms (DS) compared to patients without DS. Significantly lower levels of anti-inflammatory cytokine IL-10 were found in patients with DS compared to patients without DS. Considerable heterogeneity was detected in the analysis for most inflammatory markers. CONCLUSION: We found evidence for an association of higher levels of pro-inflammatory and lower anti-inflammatory cytokines and DS in patients with CKD/ESKF. Clinical trials are needed to investigate whether anti-inflammatory therapies will be effective in the prevention and treatment of DS in these patients with multiple comorbidities.

Investigating inflammation in depression in the chronically ill: Theoretical model and perspectives.

BACKGROUND: Inflammation is a risk factor for chronic physical illnesses. Evidence is building that inflammation is also a risk factor for mental illnesses making inflammation a common mechanism which could explain the high comorbidity between mental and physical illnesses. METHODS: Based on a systematic search, a review on factors associated with inflammation in the depressed chronically ill has been conducted. Relevant articles have been selected according to the methodological considerations (scope, sample size, type of analysis and bias). RESULTS: Five categories of factors mediate the association between chronic physical and mental illnesses: (1) social-demographic factors, (2) social-economic background, (3) adverse health behaviours, (4) psychological stress and (5) genetics. Psychological therapies and medication also moderate this association. A theoretical model of the interplay between inflammation, depression and chronic physical illness is then presented. DISCUSSION: Inflammation contribute to both chronic physical and mental illnesses. These conclusions support future advances in clinical and research practice, as well as training and education.

Association of Anxiety With Pain and Disability but Not With Increased Measures of Inflammation in Adolescent Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: To explore whether anxiety and depression are associated with clinical measures of disease for adolescent patients with juvenile idiopathic arthritis (JIA) and whether anxiety and depression are associated with increased peripheral proinflammatory cytokine levels in adolescent patients with JIA and in healthy adolescent controls. METHODS: A total of 136 patients with JIA and 88 healthy controls ages 13-18 years completed questionnaires on anxiety and depressive symptoms. For patients with JIA, pain, disability, physician global assessment (using a visual analog scale [VAS]), and number of joints with active inflammation (active joint count) were recorded. In a subsample, we assessed lipopolysaccharide-stimulated interleukin 6 (IL-6) production from peripheral blood mononuclear cells, serum IL-6, cortisol, and C-reactive protein levels. Data were analyzed by linear regression analysis. RESULTS: Levels of anxiety and depressive symptoms in patients with JIA were not significantly different than those in healthy controls. For patients with JIA, anxiety was significantly associated with disability (ß = 0.009, P = 0.002), pain (ß = 0.029, P = 0.011), and physician global assessment VAS (ß = 0.019, P = 0.012), but not with active joint count (ß = 0.014, P = 0.120). Anxiety was not associated with any laboratory measures of inflammation for JIA patients. These relationships were also true for depressive symptoms. For healthy controls, there was a trend toward an association of anxiety (but not depressive symptoms) with stimulated IL-6 (ß = 0.004, P = 0.052). CONCLUSION: Adolescent patients with JIA experience equivalent levels of anxiety and depressive symptoms as healthy adolescents. For adolescent patients with JIA, anxiety and depressive symptoms are associated with pain, disability, and physician global assessment VAS, but not with inflammation.

Self-Reported Sensory Impairments and Changes in Cognitive Performance: A Longitudinal 6-Year Follow-Up Study of English Community-Dwelling Adults Aged ⩾50 Years.

Objective: To investigate the influence of single and dual sensory impairments prospectively on cognition in adults aged ⩾50 years. Method: Community-dwelling English adults (n = 4,621) were followed up from 2008 to 2014. Self-reported hearing and vision were collected in 2008. Change in cognitive performance on working memory and executive function between 2008 and 2014 was evaluated. Results: Compared with good hearing and good vision, respectively, poor hearing and poor vision were associated with worse cognitive function (hearing: unstandardized coefficient B = 0.83, 95% Confidence Interval [CI] = [0.29, 1.37]; vision: B = 1.61, 95% CI = [0.92, 2.29] adjusted for age, sex, baseline cognition). Compared with no sensory impairment, dual sensory impairment was associated with worse cognition (B = 2.30, 95% CI = [1.21, 3.39] adjusted for age, sex, baseline cognition). All associations remained after further adjustment for sociodemographic characteristics, lifestyle factors, chronic conditions, falls, mobility, depression, and lack of companionship. Discussion: The findings are important as age-related sensory impairments are often preventable or modifiable, which may prevent or delay cognitive impairment.

Inflammation associated with coronary heart disease predicts onset of depression in a three-year prospective follow-up: A preliminary study.

Depression frequently co-occurs with coronary heart disease (CHD), worsening clinical outcomes of both, and inflammation has been proposed as a biological link between these two disorders. The aim of the present study was to investigate the role of inflammation in the development of depression in CHD patients during a 3-year follow-up. We examined the inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), measured at baseline, as a potential predictor of later onset of depression. We recruited 89 CHD patients, who were assessed at baseline and then every 6 months, for three years. The sample included, at baseline, 25 depressed and 64 non-depressed CHD patients, as confirmed by Clinical Interview Schedule Revised (CIS-R). Depressive symptoms were assessed at baseline and all follow-up points by the Patient Health Questionnaire-9 (PHQ-9). In all CHD patients (n = 89), we found a significant positive correlation between hsCRP levels and the severity of depressive symptoms at baseline (PHQ-9, r = 0.23, p = 0.032). During follow-up, n = 21 patients (of the 64 non-depressed at baseline) developed depression, defined as being PHQ-9 positive (a score ≥ 10) in at least one follow-up assessment. Of these, n = 9 subjects were defined as developing clinically-significant depression, that is, having a positive PHQ-9 in at least 3 of the 6 follow-up assessments, implying a duration of symptoms of at least one year. We found that increased hsCRP values at baseline predicted future onset of depression. Specifically, baseline hsCRP values were higher in patients who later developed clinically-significant depression (mean ±â€¯SD; 6.76 ±â€¯6.52 mg/L) compared with never-depressed (2.77 ±â€¯3.13 mg/L; F(1,48) = 7.29, p = 0.010), even after controlling for baseline PHQ-9 scores. In conclusion, inflammation in CHD patients is associated with future development of clinically-significant depression. HsCRP, a reliable and ready-to-use biological marker of inflammation, may help to identify depression high-risk phenotypes even among CHD patients, who already have high baseline inflammation. Our study conveys important preliminary findings that will require further replication but that have the potential to affect the mental and physical health of a vulnerable group of individuals.

Long work hours, weekend working and depressive symptoms in men and women: findings from a UK population-based study.

BACKGROUND: Globalised and 24/7 business operations have fuelled demands for people to work long hours and weekends. Research on the mental health effects of these intensive temporal work patterns is sparse, contradictory or has not considered gender differences. Our objective was to examine the relationship between these work patterns and depressive symptoms in a large nationally representative sample of working men and women in the UK. METHOD: The current study analysed data from Understanding Society, the UK Household Longitudinal Study, of 11 215 men and 12 188 women in employment or self-employment at the time of the study. Ordinary least squares regression models, adjusted for potential confounders and psychosocial work factors, were used to estimate depressive symptoms across categories of work hours and weekend work patterns. RESULTS: Relative to a standard 35-40 hours/week, working 55 hours/week or more related to more depressive symptoms among women (ß=0.75, 95% CI 0.12 to 1.39), but not for men (ß=0.24, 95% CI -0.10 to 0.58). Compared with not working weekends, working most or all weekends related to more depressive symptoms for both men (ß=0.34, 95% CI 0.08 to 0.61) and women (ß=0.50, 95% CI 0.20 to 0.79); however, working some weekends only related to more depressive symptoms for men (ß=0.33, 95% CI 0.11 to 0.55), not women (ß=0.17, 95% CI -0.09 to 0.42). CONCLUSION: Increased depressive symptoms were independently linked to working extra-long hours for women, whereas increased depressive symptoms were associated with working weekends for both genders, suggesting these work patterns may contribute to worse mental health.

Combined influence of depressive symptoms and systemic inflammation on all-cause and cardiovascular mortality: evidence for differential effects by gender in the English Longitudinal Study of Ageing.

BACKGROUND: Depressive symptoms and inflammation are risk factors for cardiovascular disease (CVD) and mortality. We investigated the combined association of these factors with the prediction of CVD and all-cause mortality in a representative cohort of older men and women. METHODS: We measured C-reactive protein (CRP) and depressive symptoms in 5328 men and women aged 52-89 years in the English Longitudinal Study of Ageing. Depressive symptoms were measured using the eight-item Centre for Epidemiological Studies Depression Scale. CRP was analysed from peripheral blood. Mortality was ascertained from national registers and associations with depressive symptoms and inflammation were estimated using Cox proportional hazard models. RESULTS: We identified 112 CVD related deaths out of 420 all-cause deaths in men and 109 CVD related deaths out of 334 all-cause deaths in women over a mean follow-up of 7.7 years. Men with both depressive symptoms and high CRP (3-20 mg/L) had an increased risk of CVD mortality (hazard ratio; 95% confidence interval: 3.89; 2.04-7.44) and all-cause mortality (2.40; 1.65-3.48) after adjusting for age, socioeconomic variables and health behaviours. This considerably exceeds the risks associated with high CRP alone (CVD 2.43; 1.59-3.71, all-cause 1.49; 1.20-1.84). There was no significant increase in mortality risk associated with depressive symptoms alone in men. In women, neither depressive symptoms or inflammation alone or the combination of both significantly predicted CVD or all-cause mortality. CONCLUSIONS: The combination of depressive symptoms and increased inflammation confers a considerable increase in CVD mortality risk for men. These effects appear to be independent, suggesting an additive role.

Does the Mediterranean Diet Protect against Stress-Induced Inflammatory Activation in European Adolescents? The HELENA Study.

Stress increases inflammation but whether adherence to Mediterranean diet counteracts this association and how early can these effects be observed is not well known. We tested whether (1) cortisol is associated to inflammation, (2) cortisol is associated to the adolescent Mediterranean diet score (aMDS), (3) aMDS lessens inflammation, (4) aMDS associates with cortisol levels and inflammation. Two hundred and forty-two adolescents (137 females; 12.5⁻17.5 years old) provided salivary cortisol, blood and 2-day 24-h dietary recall from which aMDS was derived. Cortisol levels were associated with increased tumor necrosis factor (TNF-α B = 11.887, p = 0.001) when adjusted for age, gender, parental education and body mass index (BMI). Moreover, cortisol levels were inversely associated to adherence to the Mediterranean Diet (B = -1.023, p = 0.002). Adolescents with higher adherence to aMDS had lower levels of interleukins (IL) IL-1, IL-2, IL-6 and TNF-α, compared to those who did not adhere. The association between cortisol and TNF-α was no longer significant when aMDS was included in the model (B = 6.118, p = 0.139). In addition, comparing lower and higher aMDS groups, the association between cortisol and TNF-α was only observed in those with lower aMDS adherence. Our study suggests that adherence to the Mediterranean Diet may counteract the effect of stress on inflammatory biomarkers which may contribute to decreasing the risk of future mental health.

The effects of six-day SSRI administration on diurnal cortisol secretion in healthy volunteers.

RATIONALE: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been widely reported in depression, and evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might exert their therapeutic effects through altering cortisol secretion. OBJECTIVE: This study assessed the effects of SSRI administration on diurnal cortisol secretion in healthy volunteers. METHODS: Sixty-four healthy men and women were randomised to receive either 10 mg escitalopram or placebo for six days in a double-blind fashion. On day six of medication, saliva samples were obtained at home for measurement of diurnal cortisol parameters (cortisol slope, cortisol awakening response, total daily cortisol output). RESULTS: Women receiving escitalopram had significantly steeper cortisol slopes across the day compared with those receiving placebo (F(1, 36) = 7.54, p = 0.009). This alteration in cortisol slope was driven by increases in waking cortisol levels (F(1, 35) = 9.21, p = 0.005). Escitalopram did not have any significant effect on the cortisol awakening response or the total daily cortisol output. CONCLUSIONS: Flattened cortisol slopes have been seen in depression. The results of this study suggest that escitalopram might exert its therapeutic effect in women in part through correction of a flattened diurnal cortisol rhythm.

Psychosocial stress and inflammation driving tryptophan breakdown in children and adolescents: A cross-sectional analysis of two cohorts.

BACKGROUND: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group. METHODS: Two cross-sectional population-based samples of children/adolescents (8-18 y) were available: 315 from the European HELENA study and 164 from the Belgian ChiBS study. In fasting serum samples, tryptophan, kynurenine, kynurenic acid, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-É£, soluble vascular adhesion molecule 1 (sVCAM1) and soluble intercellular adhesion molecule 1 (sICAM1) were measured. Psychological stress was measured by stress reports (subjective) and cortisol (objective - awakening salivary cortisol or hair cortisol). Linear regressions with stress or inflammation as predictor were adjusted for age, sex, body mass index, puberty, socio-economic status and country. RESULTS: In both cohorts, inflammation as measured by higher levels of CRP, sVCAM1 and sICAM1 was associated with kynurenine/tryptophan ratio and thus enhanced tryptophan breakdown (beta: 0.145-0.429). Psychological stress was only associated with tryptophan breakdown in the presence of higher inflammatory levels (TNF-α in both populations). CONCLUSIONS: Inflammatory levels were replicable key in enhancing tryptophan breakdown along the kynurenine pathway, even at young age and in a non-clinical sample. The stress-inflammation interaction indicated that only the stress exposures inducing higher inflammatory levels (or in an already existing inflammatory status) were associated with more tryptophan breakdown. This data further contributes to our understanding of pathways to disease development, and may help identifying those more likely to develop stress or inflammation-related illnesses.

Depressive symptoms, pain and disability for adolescent patients with juvenile idiopathic arthritis: results from the Childhood Arthritis Prospective Study.

Objectives: To determine if depressive symptoms assessed near diagnosis associate with future measures of pain, disability and disease for adolescent patients diagnosed with JIA. Methods: Data were analysed from JIA patients aged 11-16 years recruited to the Childhood Arthritis Prospective Study, a UK-based inception cohort of childhood-onset arthritis. Depressive symptoms (using the Mood and Feelings Questionnaire; MFQ), active and limited joint count, disability score (Childhood Health Assessment Questionnaire), pain visual analogue scale and patient's general evaluation visual analogue scale were collected. Associations between baseline measures (first visit to paediatric rheumatologist) were analysed using multiple linear regression. Linear mixed-effect models for change in the clinical measures of disease over 48 months were estimated including MFQ as an explanatory variable. Results: Data from 102 patients were analysed. At baseline, median (IQR) age was 13.2 years (11.9-14.2 years) and 14.7% scored over the MFQ cut-off for major depressive disorder. At baseline, depressive symptoms significantly associated with all clinical measures of disease (P ⩽ 0.01). High baseline depressive symptoms scores predicted worse pain (P ⩽ 0.005) and disability (P ⩽ 0.001) 12 months later but not active and limited joint counts. Conclusions: Adolescent patients with JIA and depressive symptoms had more active joints, pain and disability at the time of their first specialist appointment. The associations between baseline depression and both pain and disability continued for at least one year, however, this was not the case for active joint count.

The effect of beta-adrenergic blockade on inflammatory and cardiovascular responses to acute mental stress.

Acute mental stress elicits increases in plasma cytokine concentrations in humans, but the underlying mechanisms remain poorly understood. We assessed the impact of beta-adrenergic blockade on plasma interleukin 6 (IL-6) and IL-1 receptor antagonist (IL-1Ra) responses in a parallel group, double-blind randomised placebo-controlled trial involving 64 healthy young adult volunteers. Participants were administered 80 mg slow-release propranolol or placebo daily for 7 days before the stress testing session in which responses to 3 behavioural challenges (public speaking, mirror tracing, mental arithmetic) were evaluated. Propranolol administration was associated with reduced baseline levels of heart rate and IL-1Ra, and systolic blood pressure (BP) in men. Tasks stimulated increased plasma IL-6 concentrations sampled 45 min and 75 min after challenge, but these responses were blocked by propranolol in men (p < 0.001). Propranolol did not influence IL-6 responses in women, or IL-1Ra in either sex. Blood pressure and heart rate increased markedly during the tasks, but there was no differential stress reactivity in propranolol and placebo conditions. The results of the study support a role of sympathetic nervous system activation in stimulating acute IL-6 responses to stress, but only in men. The reasons for the differences between men and women remain to be resolved.

Self-reported vision impairment and incident prefrailty and frailty in English community-dwelling older adults: findings from a 4-year follow-up study.

BACKGROUND: Little is known about vision impairment and frailty in older age. We investigated the relationship of poor vision and incident prefrailty and frailty. METHODS: Cross-sectional and longitudinal analyses with 4-year follow-up of 2836 English community-dwellers aged ≥60 years. Vision impairment was defined as poor self-reported vision. A score of 0 out of the 5 Fried phenotype components was defined as non-frail, 1-2 prefrail and ≥3 as frail. Participants non-frail at baseline were followed-up for incident prefrailty and frailty. Participants prefrail at baseline were followed-up for incident frailty. RESULTS: 49% of participants (n=1396) were non-frail, 42% (n=1178) prefrail and 9% (n=262) frail. At follow-up, there were 367 new cases of prefrailty and frailty among those non-frail at baseline, and 133 new cases of frailty among those prefrail at baseline. In cross-sectional analysis, vision impairment was associated with frailty (age-adjustedandsex-adjusted OR 2.53, 95% CI 1.95 to 3.30). The association remained after further adjustment for wealth, education, cardiovascular disease, diabetes, falls, cognition and depression. In longitudinal analysis, compared with non-frail participants with no vision impairment, non-frail participants with vision impairment had twofold increased risks of prefrailty or frailty at follow-up (OR 2.07, 95% CI 1.32 to 3.24). The association remained after further adjustment. Prefrail participants with vision impairment did not have greater risks of becoming frail at follow-up. CONCLUSION: Non-frail older adults who experience poor vision have increased risks of becoming prefrail and frail over 4 years. This is of public health importance as both vision impairment and frailty affect a large number of older adults.

Self-Reported Hearing Impairment and Incident Frailty in English Community-Dwelling Older Adults: A 4-Year Follow-Up Study.

OBJECTIVES: To examine the association between hearing impairment and incident frailty in older adults. DESIGN: Cross-sectional and longitudinal analyses with 4-year follow-up using data from the English Longitudinal Study of Ageing. SETTING: Community. PARTICIPANTS: Community-dwelling individuals aged 60 and older with data on hearing and frailty status (N = 2,836). MEASUREMENTS: Hearing impairment was defined as poor self-reported hearing. Having none of the five Fried frailty phenotype components (slow walking, weak grip, self-reported exhaustion, weight loss and low physical activity) was defined as not frail, having one or two as prefrail, and having three or more as frail. Participants who were not frail at baseline were followed for incident prefrailty and frailty. Participants who were prefrail at baseline were followed for incident frailty. RESULTS: One thousand three hundred ninety six (49%) participants were not frail, 1,178 (42%) were prefrail, and 262 (9%) were frail according to the Fried phenotype. At follow-up, there were 367 new cases of prefrailty and frailty among those who were not frail at baseline (n = 1,396) and 133 new cases of frailty among those who were prefrail at baseline (n = 1,178). Cross-sectional analysis showed an association between hearing impairment and frailty (age- and sex-adjusted odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.37-2.01), which remained after further adjustments for wealth, education, cardiovascular disease, cognition, and depression. In longitudinal analyses, nonfrail participants with hearing impairment were at greater risk of becoming prefrail and frail at follow-up (OR = 1.43, 95% CI = 1.05-1.95), but the association was attenuated after further adjustment. Prefrail participants with hearing impairment had a greater risk of becoming frail at follow-up (OR = 1.64, 95% CI = 1.07-2.51) even after further adjustment. CONCLUSION: Hearing impairment in prefrail older adults was associated with greater risk of becoming frail, independent of covariates, suggesting that hearing impairment may hasten the progression of frailty.

Singing modulates mood, stress, cortisol, cytokine and neuropeptide activity in cancer patients and carers.

There is growing evidence that psychosocial interventions can have psychological benefits for people affected by cancer, including improved symptoms of mental health and wellbeing and optimised immune responses. However, despite growing numbers of music interventions, particularly singing, in cancer care, there is less research into their impact. We carried out a multicentre single-arm preliminary study to assess the impact of singing on mood, stress and immune response in three populations affected by cancer: carers (n = 72), bereaved carers (n = 66) and patients (n = 55). Participants were excluded if pregnant or if they were currently being treated with chemotherapy, radiotherapy or oral immunosuppressive drugs. Participants were regular participants in five choirs across South Wales and took part in one hour of group singing. Before and after singing, visual analogue mood scales, stress scales and saliva samples testing for cortisol, beta-endorphin, oxytocin and ten cytokines were taken. Across all five centres and in all four participant groups, singing was associated with significant reductions in negative affect and increases in positive affect (p < .01) alongside significant increases in cytokines including GM-CSF, IL17, IL2, IL4 and sIL-2rα (all p < .01). In addition, singing was associated with reductions in cortisol, beta-endorphin and oxytocin levels. This study provides preliminary evidence that singing improves mood state and modulates components of the immune system. Further work is needed to ascertain how this differs for more specific patient groups and whether repeat exposure could lead to meaningful, longitudinal effects.

Hearing impairment and incident disability and all-cause mortality in older British community-dwelling men.

BACKGROUND AND OBJECTIVE: hearing impairment is common in older adults and has been implicated in the risk of disability and mortality. We examined the association between hearing impairment and risk of incident disability and all-cause mortality. DESIGN AND SETTING: prospective cohort of community-dwelling older men aged 63-85 followed up for disability over 2 years and for all-cause mortality for 10 years in the British Regional Heart Study. METHODS: data were collected on self-reported hearing impairment including hearing aid use, and disability assessed as mobility limitations (problems walking/taking stairs), difficulties with activities of daily living (ADL) and instrumental ADL (IADL). Mortality data were obtained from the National Health Service register. RESULTS: among 3,981 men, 1,074 (27%) reported hearing impairment. Compared with men with no hearing impairment, men who could hear and used a hearing aid, and men who could not hear despite a hearing aid had increased risks of IADL difficulties (age-adjusted OR 1.86, 95% CI 1.29-2.70; OR 2.74, 95% CI 1.53-4.93, respectively). The associations remained after further adjustment for covariates including social class, lifestyle factors, co-morbidities and social engagement. Associations of hearing impairment with incident mobility limitations, incident ADL difficulties and all-cause mortality were attenuated on adjustment for covariates. CONCLUSION: this study suggests that hearing problems in later life could increase the risk of having difficulties performing IADLs, which include more complex everyday tasks such as shopping and light housework. However, further studies are needed to determine the associations observed including the underlying pathways.

Effects of Group Drumming Interventions on Anxiety, Depression, Social Resilience and Inflammatory Immune Response among Mental Health Service Users.

UNLABELLED: Growing numbers of mental health organizations are developing community music-making interventions for service users; however, to date there has been little research into their efficacy or mechanisms of effect. This study was an exploratory examination of whether 10 weeks of group drumming could improve depression, anxiety and social resilience among service users compared with a non-music control group (with participants allocated to group by geographical location.) Significant improvements were found in the drumming group but not the control group: by week 6 there were decreases in depression (-2.14 SE 0.50 CI -3.16 to -1.11) and increases in social resilience (7.69 SE 2.00 CI 3.60 to 11.78), and by week 10 these had further improved (depression: -3.41 SE 0.62 CI -4.68 to -2.15; social resilience: 10.59 SE 1.78 CI 6.94 to 14.24) alongside significant improvements in anxiety (-2.21 SE 0.50 CI -3.24 to -1.19) and mental wellbeing (6.14 SE 0.92 CI 4.25 to 8.04). All significant changes were maintained at 3 months follow-up. Furthermore, it is now recognised that many mental health conditions are characterised by underlying inflammatory immune responses. Consequently, participants in the drumming group also provided saliva samples to test for cortisol and the cytokines interleukin (IL) 4, IL6, IL17, tumour necrosis factor alpha (TNFα), and monocyte chemoattractant protein (MCP) 1. Across the 10 weeks there was a shift away from a pro-inflammatory towards an anti-inflammatory immune profile. Consequently, this study demonstrates the psychological benefits of group drumming and also suggests underlying biological effects, supporting its therapeutic potential for mental health. TRIAL REGISTRATION: ClinicalTrials.gov NCT01906892.

Higher serum dehydroepiandrosterone sulfate protects against the onset of depression in the elderly: Findings from the English Longitudinal Study of Aging (ELSA).

Depression is one of the major causes of disability worldwide, but the complete etiology of depression is not fully understood. Dehydroepiandrosterone (DHEA) and its sulphated form DHEA(S) have been associated with mood and healthy aging. Associations with mental illness over the middle to late years of life have not yet been extensively investigated in large, western community-dwelling samples. The aim of this study was to investigate whether low DHEA(S) levels are associated with the development of depressive symptoms in a large longitudinal cohort study of older men and women. We assessed data from English Longitudinal Study of Aging (ELSA) to evaluate the association of DHEA(S) levels and depressive symptoms measured by Center for Epidemiologic Studies Scale (CES-D) at baseline (n=3083) and at 4-year follow-up (n=3009). At baseline, there was an inverse association between DHEA(S) and depressive symptoms (B=-0.252, p=0.014). Adjustments for physical illnesses, impairments in cognitive function and health behaviors abolished this association (p=0.109) at baseline. Decreased DHEA(S) levels at baseline also predicted incident depression at 4-year follow-up (B=-0.332, p<0.001). In conclusion, higher DHEA(S) levels were associated with reduced risk of developing depressive symptoms in both men and women.

Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy.

RATIONALE: There is a substantial unmet need for biomarkers to predict treatment response in major depressive disorder (MDD). Evidence has converged on activation of the inflammatory response system as a fundamental mechanism underlying MDD. OBJECTIVES: By investigating circulating leukocyte subsets quantified by fluorescence-activated cell sorting (FACS) analysis before treatment, we aim to predict antidepressant response. METHODS: Forty medication-free inpatients with melancholic, non-psychotic depression before treatment with either venlafaxine or imipramine and 40 age- and gender-matched healthy controls were included. Leukocyte subsets were quantified by FACS analysis using frozen peripheral blood mononuclear cells (PBMC) collected prior to and after 7 weeks of treatment with either venlafaxine (375 mg/day) or imipramine (blood level 200-300 ng/ml). Response was defined as at least 50 % reduction of the baseline Hamilton Rating Scale for Depression (HAM-D) score. RESULTS: Prior to treatment, MDD patients showed reduced percentages of CD4(+)CD25(high)Foxp3(+) T regulatory (Treg) cells when compared with controls (1.5 ± 0.6 vs. 1.8 ± 0.6, p = .037). After treatment, robust rises in Treg cells were observed in patients (1.8 ± 0.7, p < .001), yet Treg cells were not predictors of the clinical outcome of treatment. Antidepressant non-responders showed increased CD8(+) cytotoxic T cell percentages (24.0 ± 8.6 vs. 15.9 ± 5.9, p = .004) and decreased natural killer (NK) cell percentages (14.0 ± 6.9 vs. 21.4 ± 11.9, p = .020) compared with responders before treatment. Both lymphocyte levels were not significantly modulated by treatment. CONCLUSION: In melancholic MDD, FACS analysis of circulating leukocyte subpopulations might help to discriminate between patients with high or low responsiveness to antidepressant treatment.