Physical activity, low-grade inflammation, and psychological responses to the COVID-19 pandemic among older adults in England.

Mental health responses to the COVID-19 pandemic have been widely studied, but less is known about the potentially protective role of physical activity (PA) and the impact of low-grade inflammation. Using a sample of older adults from England, this study tested (1) if pre-pandemic PA and its changes during the pandemic were associated with mental health responses; (2) if older adults with low-grade inflammation experienced greater increases in depression and anxiety, compared to pre-pandemic levels; (3) if PA attenuated the association between inflammation and depression/anxiety. The study used data from the English Longitudinal Study of Ageing, a cohort study following a national sample aged 50+. Information on mental health and PA were collected before the pandemic (2016/17 and 2018/19) and during November and December 2020. Inflammation was ascertained using pre-pandemic C-reactive protein (CRP). Analyses were adjusted for sociodemographic and health-related factors and pre-pandemic mental health. Increasing PA from before to during the pandemic was linked to reduced odds of depression (OR = 0.955, 95%CI [0.937, 0.974]) and anxiety (OR = 0.954, 95%CI [0.927; 0.982]). Higher pre-pandemic PA was associated with reduced odds of depression (OR = 0.964, 95%CI [0.948, 0.981]) and anxiety (OR = 0.976, 95%CI [0.953, 1.000]), whereas elevated CRP was associated with 1.343 times higher odds of depression (95%CI [1.100, 1.641]). PA did not attenuate the inflammation-depression association. The findings suggest that PA may contribute to psychological resilience among older adults, independently of inflammation. Further research is needed to explore the psychobiological pathways underlying this protective mechanism.

The role of loneliness in the association between sexual orientation and depressive symptoms among older adults: A prospective cohort study.

BACKGROUND: This study aims to understand the mechanisms contributing to the elevated risk of depression among sexual minority older adults compared to heterosexuals. Specifically, the role of loneliness as a potential mediator is investigated to inform targeted interventions for preventing depression in sexual minority populations. METHODS: Data from the English Longitudinal Study of Ageing, focusing on adults aged over 50, were analysed. Sexual orientation (sexual minority or heterosexual) and loneliness scores (UCLA scale) were assessed at wave six (2010-2011), while depressive symptoms (CESD) were assessed at wave seven (2013-14). Linear regression models and mediation analyses, using g-computation formula and adjusted for confounders, were conducted. RESULTS: The sample included 6794 participants, with 478 (7.0 %) identifying as sexual minorities. After adjustments, sexual minorities scored higher on depressive symptoms at wave seven (mean difference): 0.23, 95 % CI 0.07 to 0.39) and loneliness at wave six (MD: 0.27, 95 % CI 0.08 to 0.46). Loneliness was positively associated with depressive symptoms (coefficient: 0.27, 95 % CI 0.26 to 0.29). In mediation analyses, loneliness explained 15 % of the association between sexual orientation and subsequent depressive symptoms. LIMITATIONS: The dataset used sexual behaviour rather than desire and identity, potentially skewing representation of sexual minorities. Additionally, transgender older adults were not included due to limited gender diversity reported within the ELSA dataset. CONCLUSIONS: Loneliness appears to be a significant modifiable mechanism contributing to the heightened risk of depressive symptoms in sexual minority older adults compared with their heterosexual counterparts.

Immune-neuroendocrine patterning and response to stress. A latent profile analysis in the English longitudinal study of ageing.

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress. Using data from the English Longitudinal Study of Ageing (ELSA), we first identified the latent structure of immune-neuroendocrine activity (indexed by high sensitivity C-reactive protein [CRP], fibrinogen [Fb], hair cortisol [cortisol], and insulin growth-factor-1 [IGF-1]), within a population-based cohort using latent profile analysis (LPA). Then, we determined whether life stress was associated with membership of different immune-neuroendocrine profiles. We followed 4,934 male and female participants, with a median age of 65 years, over a four-year period (2008-2012). A three-class LPA solution offered the most parsimonious fit to the underlying immune-neuroendocrine structure in the data, with 36 %, 40 %, and 24 % of the population belonging to profiles 1 (low-risk), 2 (moderate-risk), and 3 (high-risk), respectively. After adjustment for genetic predisposition, sociodemographics, lifestyle, and health, higher exposure to stress was associated with a 61 % greater risk of belonging to the high-risk profile (RRR: 1.61; 95 %CI = 1.23-2.12, p = 0.001), but not the moderate-risk profile (RRR = 1.10, 95 %CI = 0.89-1.35, p = 0.401), as compared with the low-risk profile four years later. Our findings extend existing knowledge on psychoneuroimmunological processes, by revealing how inflammation and neuroendocrine activity cluster in a representative sample of older adults, and how stress exposure was associated with immune-neuroendocrine responses over time.

Testing the causal relationships of physical activity and sedentary behaviour with mental health and substance use disorders: a Mendelian randomisation study.

Observational studies suggest that physical activity can reduce the risk of mental health and substance use disorders. However, it is unclear whether this relationship is causal or explained by confounding bias (e.g., common underlying causes or reverse causality). We investigated the bidirectional causal relationship of physical activity (PA) and sedentary behaviour (SB) with ten mental health and substance use disorders, applying two-sample Mendelian Randomisation (MR). Genetic instruments for the exposures and outcomes were derived from the largest available, non-overlapping genome-wide association studies (GWAS). Summary-level data for objectively assessed PA (accelerometer-based average activity, moderate activity, and walking) and SB and self-reported moderate-to-vigorous PA were obtained from the UK Biobank. Data for mental health/substance use disorders were obtained from the Psychiatric Genomics Consortium and the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. MR estimates were combined using inverse variance weighted meta-analysis (IVW). Sensitivity analyses were conducted to assess the robustness of the results. Accelerometer-based average PA was associated with a lower risk of depression (b = -0.043, 95% CI: -0.071 to -0.016, effect size[OR] = 0.957) and cigarette smoking (b = -0.026; 95% CI: -0.035 to -0.017, effect size[ß] = -0.022). Accelerometer-based SB decreased the risk of anorexia (b = -0.341, 95% CI: -0.530 to -0.152, effect size[OR] = 0.711) and schizophrenia (b = -0.230; 95% CI: -0.285 to -0.175, effect size[OR] = 0.795). However, we found evidence of reverse causality in the relationship between SB and schizophrenia. Further, PTSD, bipolar disorder, anorexia, and ADHD were all associated with increased PA. This study provides evidence consistent with a causal protective effect of objectively assessed but not self-reported PA on reduced depression and cigarette smoking. Objectively assessed SB had a protective relationship with anorexia. Enhancing PA may be an effective intervention strategy to reduce depressive symptoms and addictive behaviours, while promoting sedentary or light physical activities may help to reduce the risk of anorexia in at-risk individuals.

Immune-Neuroendocrine Patterning and Response to Stress. A latent profile analysis in the English Longitudinal Study of Ageing.

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress. Using data from the English Longitudinal Study of Ageing (ELSA), we first identified the latent structure of immune-neuroendocrine activity (indexed by high sensitivity C-reactive protein [CRP], fibrinogen [Fb], hair cortisol [cortisol], and insulin growth-factor-1 [IGF-1]), within a population-based cohort using latent profile analysis (LPA). Then, we determined whether life stress was associated with membership of different immune-neuroendocrine profiles. We followed 4,934 male and female participants with a median age of 65 years over a four-year period (2008-2012). A three-class LPA solution offered the most parsimonious fit to the underlying immune-neuroendocrine structure in the data, with 36%, 40%, and 24% of the population belonging to profiles 1 (low-risk), 2 (moderate-risk), and 3 (high-risk), respectively. After adjustment for genetic predisposition, sociodemographics, lifestyle, and health, higher exposure to stress was associated with a 61% greater risk of belonging to the high-risk profile (RRR: 1.61; 95%CI=1.23-2.12, p=0.001), but not the moderate-risk profile (RRR=1.10, 95%CI=0.89-1.35, p=0.401), as compared with the low-risk profile four years later. Our findings extend existing knowledge on psychoneuroimmunological processes, by revealing how inflammation and neuroendocrine activity cluster in a representative sample of older adults, and how stress exposure was associated with immune-neuroendocrine responses over time.

The interactive association of adverse childhood experiences and polygenic susceptibility with depressive symptoms and chronic inflammation in older adults: a prospective cohort study.

BACKGROUND: Adverse childhood experiences (ACEs) and genetic liability are important risk factors for depression and inflammation. However, little is known about the gene-environment (G × E) mechanisms underlying their aetiology. For the first time, we tested the independent and interactive associations of ACEs and polygenic scores of major depressive disorder (MDD-PGS) and C-reactive protein (CRP-PGS) with longitudinal trajectories of depression and chronic inflammation in older adults. METHODS: Data were drawn from the English longitudinal study of ageing (N~3400). Retrospective information on ACEs was collected in wave3 (2006/07). We calculated a cumulative risk score of ACEs and also assessed distinct dimensions separately. Depressive symptoms were ascertained on eight occasions, from wave1 (2002/03) to wave8 (2016/17). CRP was measured in wave2 (2004/05), wave4 (2008/09), and wave6 (2012/13). The associations of the risk factors with group-based depressive-symptom trajectories and repeated exposure to high CRP (i.e. ⩾3 mg/L) were tested using multinomial and ordinal logistic regression. RESULTS: All types of ACEs were independently associated with high depressive-symptom trajectories (OR 1.44, 95% CI 1.30-1.60) and inflammation (OR 1.08, 95% CI 1.07-1.09). The risk of high depressive-symptom trajectories (OR 1.47, 95% CI 1.28-1.70) and inflammation (OR 1.03, 95% CI 1.01-1.04) was also higher for participants with higher MDD-PGS. G×E analyses revealed that the associations between ACEs and depressive symptoms were larger among participants with higher MDD-PGS (OR 1.13, 95% CI 1.04-1.23). ACEs were also more strongly related to inflammation in participants with higher CRP-PGS (OR 1.02, 95% CI 1.01-1.03). CONCLUSIONS: ACEs and polygenic susceptibility were independently and interactively associated with elevated depressive symptoms and chronic inflammation, highlighting the clinical importance of assessing both ACEs and genetic risk factors to design more targeted interventions.

Excess body weight and specific types of depressive symptoms: Is there a mediating role of systemic low-grade inflammation?

OBJECTIVES: Obesity is associated with an increased risk of depression. Systemic low-grade inflammation, a plausible consequence of obesity, has also been linked to depression. However, the potential mediating effects of systemic low-grade inflammation on the association between excess body weight and specific symptom domains of depression remain uncertain. This study examined whether systemic low-grade inflammation mediated the associations of excess body weight (overweight and obesity) with subsequent overall, cognitive-affective, and somatic depressive symptoms. DESIGN: This study used a prospective cohort design. METHODS: The final analytical sample included 4,942 adults aged ≥50 years drawn from the English Longitudinal Study of Ageing (ELSA). Body mass index (BMI) and covariates were ascertained at baseline (wave 4, 2008/09). Continuous BMI scores were divided into four categories: 'normal weight' (18.5 ≤ BMI <25 kg/m2); 'overweight' (25 ≤ BMI <30 kg/m2); 'obesity' (BMI ≥30 kg/m2); in addition to 'excess body weight' ('overweight' and 'obesity' combined). Covariates included sociodemographic variables, behavioural factors, and chronic physical conditions. Serum concentrations of CRP were measured at wave 6 (2012/13). Depressive symptoms were assessed at baseline and ten years later (wave 9, 2018/19), using the 8-item Centre for Epidemiological Studies Depression (CES-D) Scale. Two symptom domains were constructed, distinguishing between cognitive-affective (depressed mood, loneliness, sadness, enjoyment in life, and happiness) and somatic (sleep problems, low energy levels, and fatigue) symptoms. Mediation analyses were performed to examine whether CRP statistically mediated the associations between BMI categories and depressive symptoms. RESULTS: In multivariable-adjusted analyses, excess body weight was associated with elevated somatic (OR = 1.231, 95% CI: 1.029, 1.473), but not cognitive-affective or overall depressive symptoms at follow-up. Higher CRP was associated with elevated somatic (OR = 1.156, 95% CI: 1.061, 1.259), but not cognitive-affective or overall depressive symptoms. CRP acted as a partial mediator (14.92%) of the association between excess body weight and elevated somatic, but not cognitive-affective, or overall depressive symptoms. CONCLUSION: Systemic low-grade inflammation may partially explain the association of excess body weight with somatic depressive symptoms, but not the associations with cognitive-affective or overall depressive symptoms.

The relationship of adverse childhood experiences, hair cortisol, C-reactive protein, and polygenic susceptibility with older adults' psychological distress during the COVID-19 pandemic.

Adverse childhood experiences (ACEs) are linked to poorer mental health outcomes, and growing evidence implicates biological and genetic pathways from early adversity to psychopathology. However, little is known about the relationship of ACEs and their underlying biological and genetic mechanisms with older people's mental health responses to the COVID-19 pandemic. We tested the associations of ACEs, hair cortisol, C-reactive protein (CRP), and polygenic scores (PGS) with depression, anxiety, and loneliness among older adults during the COVID-19 pandemic, accounting for the potential interplay of ACEs with biological and genetic risk markers. Data were drawn from the English Longitudinal Study of Ageing, a prospective cohort study of older adults living in England. Retrospective information on ACEs were collected in 2006/7, while CRP and hair cortisol were measured at wave 6 (2012/13). Psychological distress was assessed before the pandemic (2018-19) and at two COVID-19 assessments in 2020 (June-July and November-December). Associations were tested on 2050 participants using linear/logistic regression models adjusted for pre-pandemic outcome measures and mixed-effect models to assess changes before and during the pandemic. The results showed that ACEs were associated with higher levels of depression (OR = 2.55[95%CI:1.81,3.59]) anxiety (OR = 1.84[95%CI:1.13,3.01]), and loneliness (b = 0.28[95%CI:0.14,0.42]) during the pandemic. Hair cortisol was related to an increased risk of depression (OR = 1.15[95%CI:1.04,1.26]), and CRP was associated with greater loneliness scores (b = 0.16[95%CI:0.03,0.30]). The relationship between cortisol and psychological distress was larger among participants with ACEs (e.g., ORdepression = 1.07[95%CI:1.00,1.14]). Further, individuals with high CRP experienced greater increases in feelings of loneliness from before to during the pandemic, compared to those with lower CRP levels (interaction effect=0.23; 95%CI:0.1-0.37). Individuals with 2+ ACEs experienced greater increases in depressive symptoms compared to those with none (interaction effect=2.09; 95%CI:1.1-3.98). Higher levels of hair cortisol were also related to worse changes in depressive symptoms across timepoints (interaction effect=1.84;95%CI:1.41-2.41). These results highlight the lasting impact of biosocial vulnerabilities on older adults' mental health responses to new environmental stressors. They also implicate biological mechanisms in the pathophysiology of later-life psychological distress.

Mental health, financial, and social outcomes among older adults with probable COVID-19 infection: A longitudinal cohort study.

We investigated the immediate and longer-term impact (over 4-6 months) of probable COVID-19 infection on mental health, wellbeing, financial hardship, and social interactions among older people living in England. Data were analysed from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the pandemic (2018-19) and at two COVID-19 assessments in 2020 (June-July and November-December). The associations of probable COVID-19 infection (first COVID-19 assessment) with depression, anxiety, poor quality of life (QoL), loneliness, financial hardship, and social contact with family/friends at the first and second COVID-19 assessments were tested using linear/logistic regression and were adjusted for pre-pandemic outcome measures. Participants with probable infection had higher levels of depression and anxiety, poorer QoL, and greater loneliness scores compared with those without probable infection at both the first (ORdepression = 1.62, P-value = 0.005; ORanxiety = 1.59, P-value = 0.049; bpoorQoL = 1.34, P < 0.001; bloneliness = 0.49, P < 0.001) and second (ORdepression = 1.56, P-value = 0.003; ORanxiety = 1.55, P-value = 0.041; bpoorQoL = 1.38, P-value < 0.001; bloneliness = 0.31, P-value = 0.024) COVID-19 assessments. Participants with probable infection also experienced greater financial difficulties than those without infection at the first assessment (OR = 1.50, P-value = 0.011). Probable COVID-19 infection is associated with longer-term deterioration of mental health and wellbeing and short-term increases in financial hardship among older adults. It is important to monitor the mental health of older people affected by COVID-19 and provide additional support to those in need.

Adverse childhood experiences and severity levels of inflammation and depression from childhood to young adulthood: a longitudinal cohort study.

Adverse childhood experiences (ACEs) are associated with depression and systemic inflammation in adults. However, limited longitudinal research has tested these relationships in children and young people, and it is unclear whether inflammation is an underlying mechanism through which ACEs influence depression. We examined the longitudinal associations of several ACEs across different early-life periods with longitudinal patterns of early-life inflammation and depression in young adulthood and assessed the mediating role of inflammation. The data came from the Avon Longitudinal Study of Parents and Children (N = 3931). ACEs from the prenatal period through to adolescence were operationalised using cumulative scores, single adversities, and dimensions derived through factor analysis. Inflammation (C-reactive protein) was measured on three occasions (9-18 years) and depressive symptoms were ascertained on four occasions (18-23 years). Latent class growth analysis was employed to delineate group-based trajectories of inflammation and depression. The associations between ACEs and the inflammation/depression trajectories were tested using multinomial logistic regression analysis. Most types of ACEs across all early-life periods were associated with elevated depression trajectories, with larger associations for threat-related adversities compared with other ACEs. Bullying victimisation and sexual abuse in late childhood/adolescence were associated with elevated CRP trajectories, while other ACEs were unrelated to inflammation. Inflammation was also unrelated to depression and did not mediate the associations with ACEs. These results suggest that ACEs are consistently associated with depression, whereas the associations of inflammation with ACEs and depression are weak in young people. Interventions targeting inflammation in this population might not offer protection against depression.

Immediate and Longer-Term Changes in the Mental Health and Well-being of Older Adults in England During the COVID-19 Pandemic.

Importance: Despite the emphasis placed on the psychological impact of the COVID-19 pandemic, evidence from representative studies of older adults including pre-COVID-19 data and repeated assessments during the pandemic is scarce. Objective: To examine changes in mental health and well-being before and during the initial and later phases of the COVID-19 pandemic and test whether patterns varied with sociodemographic characteristics in a representative sample of older adults living in England. Design, Setting, and Participants: This longitudinal cohort study analyzed data from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the COVID-19 pandemic (2018 and 2019) and at 2 occasions in 2020 (June or July as well as November or December). Exposures: The COVID-19 pandemic and sociodemographic characteristics, including sex, age, partnership status, and socioeconomic position. Main Outcomes and Measures: Changes in depression (8-item Centre for Epidemiological Studies Depression scale), anxiety (7-item Generalized Anxiety Disorder scale), quality of life (12-item Control, Autonomy, Self-realization, and Pleasure scale), and loneliness (3-item Revised University of California, Los Angeles, loneliness scale) were tested before and during the COVID-19 pandemic using fixed-effects regression models. Results: Of 5146 included participants, 2723 (52.9%) were women, 4773 (92.8%) were White, and the mean (SD) age was 67.7 (10.6) years. The prevalence of clinically significant depressive symptoms increased from 12.5% (95% CI, 11.5-13.4) before the COVID-19 pandemic to 22.6% (95% CI, 21.6-23.6) in June and July 2020, with a further rise to 28.5% (95% CI, 27.6-29.5) in November and December 2020. This was accompanied by increased loneliness and deterioration in quality of life. The prevalence of anxiety rose from 9.4% (95% CI, 8.8-9.9) to 10.9% (95% CI, 10.3-11.5) from June and July 2020 to November and December 2020. Women and nonpartnered people experienced worse changes in mental health. Participants with less wealth had the lowest levels of mental health before and during the COVID-19 pandemic. Higher socioeconomic groups had better mental health overall but responded to the COVID-19 pandemic with more negative changes. Conclusions and Relevance: In this longitudinal cohort study of older adults living in England, mental health and well-being continued to worsen as the COVID-19 pandemic progressed, and socioeconomic inequalities persisted. Women and nonpartnered people experienced greater deterioration in mental health.

Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study.

Dysregulated hypothalamic-pituitary-adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3-11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = -0.20, p = 0.03), bullying (b = -0.61, p = 0.01), and emotional abuse (b = -0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = -0.56, p = 0.05). Lower cortisol levels mediated around 10-20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02-0.34]) and bullying (b = 0.18 [0.01-0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

Identifying risk factors involved in the common versus specific liabilities to substance use: A genetically informed approach.

Individuals most often use several rather than one substance among alcohol, cigarettes or cannabis. This widespread co-occurring use of multiple substances is thought to stem from a common liability that is partly genetic in origin. Genetic risk may indirectly contribute to a common liability to substance use through genetically influenced mental health vulnerabilities and individual traits. To test this possibility, we used polygenic scores indexing mental health and individual traits and examined their association with the common versus specific liabilities to substance use. We used data from the Avon Longitudinal Study of Parents and Children (N = 4218) and applied trait-state-occasion models to delineate the common and substance-specific factors based on four classes of substances (alcohol, cigarettes, cannabis and other illicit substances) assessed over time (ages 17, 20 and 22). We generated 18 polygenic scores indexing genetically influenced mental health vulnerabilities and individual traits. In multivariable regression, we then tested the independent contribution of selected polygenic scores to the common and substance-specific factors. Our results implicated several genetically influenced traits and vulnerabilities in the common liability to substance use, most notably risk taking (bstandardised = 0.14; 95% confidence interval [CI] [0.10, 0.17]), followed by extraversion (bstandardised = -0.10; 95% CI [-0.13, -0.06]), and schizophrenia risk (bstandardised = 0.06; 95% CI [0.02, 0.09]). Educational attainment (EA) and body mass index (BMI) had opposite effects on substance-specific liabilities such as cigarette use (bstandardised-EA = -0.15; 95% CI [-0.19, -0.12]; bstandardised-BMI = 0.05; 95% CI [0.02, 0.09]) and alcohol use (bstandardised-EA = 0.07; 95% CI [0.03, 0.11]; bstandardised-BMI = -0.06; 95% CI [-0.10, -0.02]). These findings point towards largely distinct sets of genetic influences on the common versus specific liabilities.

Levels of Severity of Depressive Symptoms Among At-Risk Groups in the UK During the COVID-19 Pandemic.

Importance: An immediate research priority is to investigate and monitor the psychological well-being among high-risk groups during the coronavirus disease 2019 (COVID-19) pandemic. Objective: To examine levels of severity of depressive symptoms over time among individuals with high risk in the UK during the COVID-19 pandemic. Design, Setting, and Participants: This cohort study is part of an ongoing large panel study of adults aged 18 years and older residing in the UK, the COVID-19 Social Study, established on March 21, 2020. Data analysis was conducted in May 2020. Exposures: Sociodemographic risk factors included belonging to the Black, Asian, and minority racial/ethnic communities, low socioeconomic position (SEP), and essential worker roles (eg, workers in health and social care, education, childcare, or key public services). Health-related and psychosocial risk factors included preexisting physical and mental health conditions, experience of psychological or physical abuse, and low social support. Main Outcomes and Measures: Depressive symptoms were measured on 7 occasions from March 21 to April 2, 2020, using the 9-item Patient Health Questionnaire (PHQ-9). Group-based depressive symptom trajectories were derived using latent growth mixture modeling. Results: The analytical sample comprised 51 417 adults aged 18 years and older (mean [SD] age, 48.8 [16.8] years; 26 276 [51.1%] women; 6145 members [12.0%] of Black, Asian, and minority racial/ethnic communities). Among these, 17 143 participants (33.3%) were in the lowest SEP quartile, and 11 342 participants (22.1%) were classified as essential workers. Three levels of severity of depressive symptoms were identified: low (30 850 participants [60.0%]), moderate (14 911 participants [29.0%]), and severe (5656 participants [11.0%]). After adjusting for covariates, experiences of physical or psychological abuse (odds ratio [OR], 13.16; 95% CI, 12.95-13.37; P < .001), preexisting mental health conditions (OR, 12.99; 95% CI, 12.87-13.11; P < .001), preexisting physical health conditions (OR, 3.41; 95% CI, 3.29-3.54; P < .001), low social support (OR, 12.72; 95% CI, 12.57-12.86; P < .001), and low SEP (OR, 5.22; 95% CI, 5.08-5.36; P < .001) were significantly associated with severe depressive symptoms. No significant association was found for race/ethnicity (OR, 1.07; 95% CI, 0.85-1.28; P = .56). Participants with essential worker roles were less likely to experience severe depressive symptoms (OR, 0.66; 95% CI, 0.53-0.80; P < .001). Similar patterns of associations were found for the group of participants with moderate depressive symptoms (abuse: OR, 5.34; 95% CI, 5.15-5.54; P < .001; mental health condition: OR, 4.24; 95% CI, 4.24-4.24; P < .001; physical health condition: OR, 1.89; 95% CI, 1.80-1.98; P < .001; low social support: OR, 4.71; 95% CI, 4.60-4.82; P < .001; low SEP: OR, 1.97; 95% CI, 1.87-2.08; P < .001). Conclusions and Relevance: In this cohort study of UK adults participating in the COVID-19 Social Study, people with psychosocial and health-related risk factors, as well as those with low SEP, were at the most risk of experiencing moderate or severe depressive symptoms during the COVID-19 pandemic.

Adverse childhood experiences and early life inflammation in the Avon longitudinal study of parents and children.

BACKGROUND: Adverse childhood experiences (ACEs) have been associated with poorer health across the life course. Previous studies have used cumulative risk scores (ACE scores) or individual ACEs but these two approaches have important shortcomings. ACE scores assume that each adversity is equally important for the outcome of interest and the single adversity approach assumes that ACEs do not co-occur. Latent class analysis (LCA) is an alternative approach to operationalising ACEs data, identifying groups of people co-reporting similar ACEs. Here we apply these three approaches for ACEs operationalisation with inflammation in childhood with the aim of identifying particular ACEs or ACE combinations that are particularly associated with higher inflammation in early life. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we compare ACE scores, single adversities and LCA-derived ACE clusters in their relationships with Interleukin-6 at age 9 (n = 4935) and C-Reactive Protein (CRP) at age 9 (n = 4887). ACEs included were parental separation/divorce, parental alcohol problems, parental mental health problems, parental offending, inter-parental violence, parental drug misuse, and physical, emotional and sexual abuse. RESULTS: Two thirds of the sample reported at least one ACE. Mother's mental health problems was the most frequently reported ACE (32.3 %). LCA identified four ACE classes - 'Low ACEs' (81.1 %), 'Maternal mental health problems' (10.3 %), 'Maternal mental health problems and physical abuse' (6.3 %) and 'Parental conflict, mental health problems and emotional abuse' (2.4 %). Parental separation/divorce was associated with higher IL-6. Parental alcohol problems, paternal mental health problems, parental convictions and emotional abuse were associated with lower levels of IL-6. Associations for paternal mental health problems and emotional abuse were only observed for boys. ACE score and LCA-derived ACE classes were not associated with differences in IL-6. Girls in the 'Maternal mental health problems' cluster had lower CRP levels. CONCLUSIONS: Specific adversities and adversity combinations are important for differences in childhood inflammation. Some associations were only observed for girls or boys.

Adverse childhood experiences and depressive symptoms in later life: Longitudinal mediation effects of inflammation.

BACKGROUND: Adverse childhood experiences (ACEs) have been associated with both inflammation and depression. However, few studies have examined the role of inflammation as a possible biological mechanism underlying the association of ACEs with depression in later life using longitudinal data. This study investigated the longitudinal mediation effects of inflammation in the relationship between ACEs and depressive symptoms in older adults. METHODS: We utilised data from the English Longitudinal Study of Ageing (N = 4382). ACEs (i.e. threat, family dysfunction, low parental bonding, loss experiences) were assessed retrospectively at wave 3 (2006/07). C-reactive protein (CRP), an inflammatory marker, was measured at waves 2 (2004/05), 4 (2008/09), and 6 (2012/13). Depressive symptoms were ascertained from wave 6 to 8 (2016/17). The mediation analysis was conducted using parallel process latent growth curve modelling. RESULTS: Greater ACEs cumulative exposure was associated with higher CRP and depressive symptoms at baseline (ßCRPi = 0.066[0.030-0.102]; ßDEPi = 0.149[0.115-0.183]) and with their increase over time (ßCRPs = 0.205[0.095-0.315]; ßDEPs = 0.355[0.184-0.526]). Baseline CRP levels were positively associated with baseline depressive symptoms (ßDEPi = 0.145[0.104-0.186]) and their trajectory (ßDEPs = 0.215[0.124-0.306]). The mediation analysis indicated that higher baseline CRP levels mediated respectively 7% and 5% of the total effect of ACEs cumulative exposure on the baseline value and change in depressive symptoms. These mediation effects were larger for Loss experiences (i.e. 20% and 12% respectively) than for other types of ACEs. In addition, they were independent of possible confounders and additional mediators including adult socioeconomic position and lifestyle factors. CONCLUSION: ACEs were related to higher depressive symptoms partly via elevated CRP levels. Inflammation might be one of the psychobiological mechanisms underlying the link between ACEs and depression. Psychosocial and behavioural interventions to prevent and reduce the negative impact of ACEs might help to lower the risk of inflammation and depression in the population.

Abuse, self-harm and suicidal ideation in the UK during the COVID-19 pandemic.

This study explored patterns of abuse, self-harm and thoughts of suicide/self-harm in the UK during the first month of the COVID-19 pandemic using data from the COVID-19 Social Study (n=44 775), a non-probability sample weighted to population proportions. The reported frequency of abuse, self-harm and thoughts of suicide/self-harm was higher among women, Black, Asian and minority ethnic (BAME) groups and people experiencing socioeconomic disadvantage, unemployment, disability, chronic physical illnesses, mental disorders and COVID-19 diagnosis. Psychiatric medications were the most common type of support being used, but fewer than half of those affected were accessing formal or informal support.

Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: the role of cognitive-affective and somatic symptoms.

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.

The long-term association of adverse childhood experiences with C-reactive protein and hair cortisol: Cumulative risk versus dimensions of adversity.

BACKGROUND: Exposure to adverse childhood experiences (ACEs) may lead to stress-induced upregulation of inflammatory and neuroendocrine processes. However, it remains unclear whether such effects persist into later life, and which dimensions of ACEs might have the strongest impact on these biological mechanisms. Therefore, this study investigated the effects of ACEs on C-reactive protein (CRP) and hair cortisol in a large sample of older adults, distinguishing between cumulative exposure and dimensions of ACEs. METHODS: We utilised data from the English Longitudinal Study of Ageing. ACEs were assessed through retrospective reports at wave 3(2006/07). CRP (N = 4198) was measured at waves 4(2008/09) and 6(2012/13), and hair cortisol (N = 3357) at wave 6. The effects of ACEs cumulative exposure were examined using linear and ordinal logistic regression analysis. ACEs dimensions (i.e. threat, household dysfunction, low parental bonding, and loss of an attachment figure) were identified using explorative and confirmatory factor analysis with cross-validation. All analyses were adjusted for relevant confounders. RESULTS: Participants with three or more ACEs had higher CRP levels at wave 4 and an elevated risk of high CRP concentrations across waves 4 and 6 compared with those who did not experience any ACEs. The four ACEs dimensions were all positively associated with both CRP outcomes and had similar effect sizes. In contrast, neither the cumulative score nor the dimensions of ACEs were significantly related to hair cortisol. However, there was a positive, yet small, interaction effect between ACEs and age on hair cortisol. CONCLUSION: Older adults who retrospectively reported three or more ACEs had chronically elevated CRP levels and exhibited a slightly steeper increase in hair cortisol with age. Different dimensions of ACEs had similar associations with the biomarkers.

Cardiovascular Disease and Hair Cortisol: a Novel Biomarker of Chronic Stress.

PURPOSE OF REVIEW: This review focuses on the concentration of cortisol in human hair as a biomarker of chronic stress in cardiovascular disease (CVD). We outline the cardiovascular consequences of cortisol excess and provide a comprehensive overview of recent studies investigating the relationship of hair cortisol with CVD. In addition, clinical implications and limitations of the evidence are discussed, together with directions for future research. RECENT FINDINGS: Hair cortisol may be a reliable biomarker of chronic stress since it provides quantification of total cortisol secreted into hair over several weeks. A growing body of evidence suggests that elevated hair cortisol levels are associated with both the incidence of CVD and poorer recovery and treatment outcomes. Moreover, increased hair cortisol concentration has been linked with established cardiometabolic risk factors for CVD including high blood pressure, diabetes, and adiposity. Hair cortisol is a promising biomarker of chronic cortisol excess which may contribute to both the pathogenesis and prognosis of CVD. However, the current evidence relies on small-scale cross-sectional studies. Further research adopting longitudinal designs across larger samples of CVD patients and healthy participants is required to inform the development of novel evidence-based interventions.