Depression and adverse childhood experiences: Interplay between psychosocial, biological, and genetic factors across the life course

Adverse childhood experiences (ACEs), such as abuse and family dysfunction, are among the most potent psychosocial risk factors for depression. Stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis and inflammatory systems might underlie the psychobiological impact of ACEs on depression. However, the evidence for the role of these biological mechanisms is weak owing to a limited availability of longitudinal data and other methodological issues. Furthermore, it remains unclear whether genetic influences could contribute to these relationships. This PhD consists of six studies seeking to elucidate the neuroendocrine, inflammatory, and gene-environment mechanisms through which ACEs might influence the risk of depression across the life course. Studies 1-4 focused on older adults, using data from the English Longitudinal Study of Ageing. Study 1 showed that older adults affected by ACEs exhibited chronically elevated systemic inflammation. In contrast, ACEs were unrelated to hair cortisol. Study 2 revealed that higher inflammation and cortisol levels were associated with persistent depressive symptoms over time. These relationships were stronger with somatic than with cognitive-affective symptoms. Study 3 demonstrated that ACEs were related to depression partly via elevated inflammation. Study 4 further showed that ACEs and polygenic susceptibility were independently and interactively associated with depression and inflammation. Studies 5-6 focused on young people, using data from the Twins Early Development Study and the Avon Longitudinal Study of Parents and Children. In Study 5, ACEs were associated with elevated depressive symptoms in young adulthood partly through lower salivary cortisol levels in adolescence, independently of genetic factors. Study 6 demonstrated that ACEs across different early-life periods (prenatal period, childhood, and adolescence) were associated with elevated depressive symptoms in young adulthood. In contrast, the associations of ACEs and depression with early-life inflammation were weak. These findings offer novel insights into the biological embedding of ACEs and can stimulate new mental health interventions

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

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

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

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

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

Mapping 2007-08 Tuition And Fees In Higher Education

Using data sets from US News &amp; World Report and the Association to Advance Collegiate Schools of Business, this paper isolates 10 factors that account for 90 percent of the variation in tuition and fees across 523 institutions of higher learning in the United States.&nbsp; It is hoped that the results will give guidance to schools by quantifying the costs and benefits of making a given change to their tuition and fee structure.&nbsp

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