Clinical phenotypes of depressed patients with evidence of inflammation and somatic symptoms.

Funder: MQ: Transforming Mental Health; Grant(s): MQDS17\40, MQDS17/40Whether depressed patients with evidence of inflammation are more appropriate candidates for immunotherapies is being tested in several clinical trials, which are selecting patients based on elevated C-reactive protein (CRP) and inflammation-related symptoms. However, studies of the clinical and phenotypic profile of depressed patients with elevated CRP are relatively scarce. We have investigated detailed clinical characteristics of 84 depressed patients, grouped as those with (CRP≥3 mg/L) and without (CRP<3 mg/L) inflammation. All patients met the International Classification of Diseases 10th Revision criteria for current depressive episode and had somatic symptoms of depression. We report that depressed patients with inflammation are more likely to be older (P=0.04), have higher body mass index (P<0.01), and be on non-selective serotonin reuptake inhibitor anti-depressants (P=0.04). After adjusting for potential confounders, the inflammation group had higher depression severity (adjusted mean difference, 8.82; 95% CI, 3.91-13.72), somatic symptoms (adjusted mean difference, 3.25; 95% CI, 1.58-4.92), state anxiety (adjusted mean difference, 9.25; 95% CI, 3.82-14.67), perceived stress (adjusted mean difference, 4.58; 95% CI, 1.98-7.18), and fatigue (adjusted mean difference, 9.71; 95% CI, 3.09-6.33), but not anhedonia. The inflamed group also had poorer quality of life (adjusted mean difference, -0.18; 95% CI, -0.32-0.05). At individual depressive symptom level, the inflammation group had increased guilty feelings (adjusted odds ratio [OR], 7.28; 95% CI, 2.09-31.17), pessimism (adjusted OR, 5.38; 95% CI, 1.53-22.73), concentration difficulties (adjusted OR, 4.56; 95% CI, 1.32-19.02), and indecisiveness (adjusted OR, 4.21; 95% CI, 1.15-18.54). Our findings highlight the clinical features associated with inflammation in depressed patients with somatic symptoms, including poor quality of life, supporting the need for intervention targeting this group. These results could also aid patient and outcome selection in future clinical trials testing immunotherapies in depression. Replication of these findings in larger samples is required.This work was funded by a Wellcome Trust fellowship to GMK (grant code: 201486/Z/16/Z). GMK also acknowledges funding support from Cambridgeshire and Peterborough NHS Foundation Trust R&D Department (Grant code: G101481), the BMA Foundation (J Moulton grant 2019); the MQ: Transforming Mental Health (grant code: MQDS17/40); and the Medical Research Council UK (grant codes: MC_PC_17213 and MR/S037675/1). The BMA Foundation J Moulton grant supports ÉMF and the MRC grant MC_PC_17213 supports JTP. NK is supported by the International Max Planck Research School of Translational Psychiatry (IMPRS-TP). The funding sources had no role in study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the paper for publication

Depression in patients with spondyloarthritis: prevalence, incidence, risk factors, mechanisms and management

Funder: MQ: Transforming Mental Health; FundRef: https://doi.org/10.13039/501100008162; Grant(s): MQDS17/40Funder: cambridge trust; FundRef: https://doi.org/10.13039/501100003343Depression is a major neuropsychiatric disorder common in patients with rheumatological conditions including spondyloarthritis (SpA). It is associated with higher disease activity, functional impairment, poor treatment response and quality of life in patients with musculoskeletal disorders. Using ankylosing spondylitis (AS) and psoriatic arthritis (PsA) as examples, we have reviewed the evidence regarding the burden, risk factors, potential mechanisms and clinical management of depression in spondyloarthritis. The prevalence of depression is higher in patients with AS and PsA compared with the general population, with evidence of moderate/severe depression in about 15% of patients with AS or PsA. Mild depression is even more common and estimated to be present in about 40% of patients with AS. In addition to conventional risk factors such as stressful life events and socioeconomic deprivation, increased risk of depression in SpA may be associated with disease-related factors, such as disease activity, poor quality of life, fatigue, and sleep disturbances. Emerging evidence implicates inflammation in the aetiology of depression, which could also be a shared mechanism for depression and chronic inflammatory conditions such as AS and PsA. It is imperative for clinicians to actively assess and treat depression in SpA, as this could improve treatment adherence, quality of life, and overall long-term clinical and occupational outcomes. The use of validated tools can aid recognition and management of depression in rheumatology clinics. Management of depression in SpA, especially when to refer to specialist mental health services, are discussed

Neurocognitive Performance in Depressed Patients with low-grade inflammation and somatic symptoms.

BACKGROUND: The link between inflammation and depression has been investigated extensively. Cognitive dysfunction in depression is an unmet treatment need. A better understanding of possible links between inflammation and cognition in people with depression may help to identify new treatment targets. METHODS: We report findings from a study comparing a range of cognitive functions between 80 depressed patients with (C-reactive protein ≥3 ​mg/L; n ​= ​37) and without (CRP<3 ​mg/L; n ​= ​43) evidence of inflammation. All participants met the International Classification of Diseases 10th Revision criteria for current depressive episode and had somatic symptoms of depression. All participants completed cognitive testing and clinical assessment and were screened for acute infection. RESULTS: Patients with evidence of inflammation, compared to those without, had slower psychomotor speed as measured by symbol coding task (mean difference ​= ​0.06, 95% CI ​= ​0.003-0.11) and slower reaction time, as measured by a simple movement time task (mean difference ​= ​26.56, 95% CI ​= ​-48.92 to -4.20). These effects were fully explained after controlling for age, sex, and body mass index. Measures of emotional processing, memory, and planning were comparable between two groups. CONCLUSIONS: Certain cognitive domains, particularly processing speed and reaction time may be more affected in depressed patients with evidence of low-grade inflammation and somatic symptoms. Further studies with larger samples are required for a clearer understanding of the association between inflammation and cognitive dysfunction in depression

Peripheral blood cellular immunophenotype in depression: a systematic review and meta-analysis.

Acknowledgements: We would like to thank Dr Mary-Ellen Lynall (University of Cambridge) for providing additional information regarding their study for our systematic review and meta-analysis.Funder: Medical Research Council Epidemiology Unit PhD StudentshipFunder: Versus Arthritis Award (Grant No. 22453)Funder: Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/1)Funder: NIHR Cambridge BioResourceFunder: The MQ: Transforming Mental Health (Grant No. MQDS17/40); BMA Foundation (J. Moulton Grant 2019)INTRODUCTION: Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to controls. White blood cells (WBC) both produce and are influenced by cytokines, and play key roles in orchestrating innate and adaptive immune responses, but their role in depression remains unclear. Therefore, a systematic review of studies of various WBC subsets in depression is required for a greater understanding of the nature of immune dysfunction in this illness. METHODS: We searched PubMed and PsycINFO databases (inception to 5th April 2022) and conducted a systematic review and meta-analysis of identified studies comparing absolute count and/or relative percentage of flow cytometry-derived WBC subsets between depression cases and controls. Selected studies were quality assessed. Random-effect meta-analysis was performed. RESULTS: Thirty-three studies were included and 27 studies (n = 2277) were meta-analysed. We report an increase in mean absolute counts of WBC (seven studies; standardised mean difference [SMD] = 1.07; 95% CI, 0.61-1.53; P < 0.01; I2 = 64%), granulocytes (two studies; SMD = 2.07; 95% CI, 1.45-2.68; P < 0.01; I2 = 0%), neutrophils (four studies; SMD = 0.91; 95% CI, 0.23-1.58; P < 0.01; I2 = 82%), monocytes (seven studies; SMD = 0.60; 95% CI, 0.19-1.01; P < 0.01; I2 = 66%), CD4+ helper T cells (11 studies; SMD = 0.30; 95% CI, 0.15-0.45; P < 0.01; I2 = 0%), natural killer cells (11 studies; SMD = 1.23; 95% CI, 0.38-2.08; P < 0.01; I2 = 95%), B cells (10 studies; SMD = 0.30; 95% CI, 0.03-0.57; P = 0.03; I2 = 56%), and activated T cells (eight studies; SMD = 0.45; 95% CI, 0.24-0.66; P < 0.01; I2 = 0%) in depression, compared to controls. Fewer studies reported relative percentage, indicating increased neutrophils and decreased total lymphocytes, Th1, and Th2 cells in depression. CONCLUSIONS: Depression is characterised by widespread alterations in circulating myeloid and lymphoid cells, consistent with dysfunction in both innate and adaptive immunity. Immune cells could be useful biomarkers for illness subtyping and patient stratification in future immunotherapy trials of depression, along with cytokines, other biomarkers, and clinical measures

Quantifying and Examining Reserve in Symptomatic Former National Football League Players

BACKGROUND: Repetitive head impacts (RHI) from contact sports have been associated with cognitive and neuropsychiatric disorders. However, not all individuals exposed to RHI develop such disorders. This may be explained by the reserve hypothesis. It remains unclear if the reserve hypothesis accounts for the heterogenous symptom presentation in RHI-exposed individuals. Moreover, optimal measurement of reserve in this population is unclear and likely unique from non-athlete populations. OBJECTIVE: We examined the association between metrics of reserve and cognitive and neuropsychiatric functioning in 89 symptomatic former National Football League players. METHODS: Individual-level proxies (e.g., education) defined reserve. We additionally quantified reserve as remaining residual variance in 1) episodic memory and 2) executive functioning performance, after accounting for demographics and brain pathology. Associations between reserve metrics and cognitive and neuropsychiatric functioning were examined. RESULTS: Higher reading ability was associated with better attention/information processing (β=0.25; 95%CI, 0.05–0.46), episodic memory (β=0.27; 95%CI, 0.06–0.48), semantic and phonemic fluency (β=0.24; 95%CI, 0.02–0.46; β=0.38; 95%CI, 0.17–0.59), and behavioral regulation (β=–0.26; 95%CI, –0.48, –0.03) performance. There were no effects for other individual-level proxies. Residual episodic memory variance was associated with better attention/information processing (β=0.45; 95%CI, 0.25, 0.65), executive functioning (β=0.36; 95%CI, 0.15, 0.57), and semantic fluency (β=0.38; 95%CI, 0.17, 0.59) performance. Residual executive functioning variance was associated with better attention/information processing (β=0.44; 95%CI, 0.24, 0.64) and episodic memory (β=0.37; 95%CI, 0.16, 0.58) performance. CONCLUSION: Traditional reserve proxies (e.g., years of education, occupational attainment) have limitations and may be unsuitable for use in elite athlete samples. Alternative approaches of reserve quantification may prove more suitable for this population