Risk factors for the progression to multimorbidity among UK urban working-age adults. A community cohort study.

OBJECTIVES: The progression of long-term conditions (LTCs) from zero-to-one (initiation), and from one-to-many (progression)are common trajectories that impact a person's quality of life including their ability to work. This study aimed to explore the demographic, socioeconomic, psychosocial, and health-related determinants of LTC initiation and progression, with a focus on work participation. METHODS: Data from 622 working-age adults who had completed two waves (baseline and follow-up) of the South-East London Community Health survey were analysed. Chi square tests and multinomial logistic regression were used to describe the associations between self-reported demographic, socioeconomic, psychosocial, and health-related variables, and the progression of LTCs. RESULTS: Small social networks, an increased number of stressful life events, low self-rated health, functional impairment, and increased somatic symptom severity were all associated with both the progression from zero-to-one LTC and from one LTC to multimorbidity (two or more LTCs). Renting accommodation (RRR 1.73 [95% CI 1.03-2.90]), smoking (RRR 1.91 [95% CI 1.16-3.14]) and being overweight (RRR 1.88 [95% CL 1.12-3.16]) were unique risk factors of developing initial LTCs, whereas low income (RRR 2.53 [95% CI 1.11-5.80]), working part-time (RRR 2.82 ([95% CL 1.12-7.10]), being unemployed (RRR 4.83 [95% CI 1.69-13.84]), and making an early work exit (RRR 16.86 [95% CI 3.99-71.30]) all increased the risk of progressing from one LTC to multimorbidity compared to being employed full-time. At follow-up, depression was the most prevalent LTC in the unemployed group whereas musculoskeletal conditions were the most prevalent in those working. CONCLUSIONS: The journey to multimorbidity is complex, with both common and unique risk factors. Non-full-time employment was associated with an increased risk of progression to multimorbidity. Future research should explore the risk and benefit pathways between employment and progression of LTCs. Interventions to prevent progression of LTCs should include mitigation of modifiable risk factors such as social isolation.

Depressive symptoms during early adulthood and the development of physical multimorbidity in the UK: an observational cohort study.

BACKGROUND: An understanding of whether early-life depression is associated with physical multimorbidity could be instrumental for the development of preventive measures and the integrated management of depression. We therefore aimed to map out the cumulative incidence of physical multimorbidity over adulthood, and to determine the association between the presence of depressive symptoms during early adulthood and the development of physical multimorbidity in middle age. METHODS: In this observational cohort study, we used pooled data from the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS). Cohort waves were pooled in each decade of adult life available (when cohort members were aged 26 years in the BCS and 23 years in the NCDS [baseline]; 34 years in the BCS and 33 years in the NCDS [age 34 BCS/33 NCDS]; 42 years in the BCS and NCDS [age 42 BCS/NCDS]; and 46 years in the BCS and 50 years in the NCDS [age 46 BCS/50 NCDS]). We included participants who had completed the nine-item Malaise Inventory at baseline, and did not have a history of physical multimorbidity, any physical multimorbidity at baseline, or the presence of depressive symptoms before the development of physical multimorbidity. The presence of depressive symptoms was determined using the nine-item Malaise Inventory (cutoff score ≥4). Physical multimorbidity was defined as having at least two measures of any of the following ten self-reported groups of long-term conditions: asthma or bronchitis; backache; bladder or kidney conditions; cancer; cardiovascular conditions; convulsions or epilepsy; diabetes; hearing conditions; migraine; and stomach, bowel, or gall conditions. Cumulative incidence (with 95% CI) of physical multimorbidity was calculated for each decade considered after baseline, with physical multimorbidity being assessed as both a dichotomous and categorical variable. The association between depressive symptoms and the development of physical multimorbidity was assessed using adjusted relative risk ratios (with 95% CIs). FINDINGS: Analyses included 15 845 participants, of whom 4001 (25·25%; 95% CI 24·57-25·93) had depressive symptoms at baseline and 11 844 (74·75%; 74·07-75·42) did not. The cumulative incidence of physical multimorbidity (dichotomous) ranged over the study period from 2263 (18·44%; 95% CI 17·75-18·14) of 12 273 participants at age 34 BCS/33 NCDS, to 4496 (42·90%; 41·95-43·85) of 10 481 participants at age 46 BCS/50 NCDS, and was consistently higher in participants with depressive symptoms at baseline. The adjusted relative risk of physical multimorbidity was higher in participants with depressive symptoms than in those without and remained stable over the study period (adjusted relative rate ratio 1·67, 95% CI 1·50-1·87, at age 34 BCS/33 NCDS; 1·63, 1·48-1·79, at age 42 BCS/NCDS; and 1·58, 1·43-1·73, at age 46 BCS/50 NCDS). INTERPRETATION: The presence of depressive symptoms during early adulthood is associated with an increased risk of the development of physical multimorbidity in middle age. Although further research about the drivers of this relationship is needed, these results could help to enhance the integrated management of individuals with depressive symptoms and the development of preventive strategies to reduce the effect and burden of physical multimorbidity. FUNDING: UK Medical Research Council and Guy's Charity.

Genetic risk for severe COVID-19 correlates with lower inflammatory marker levels in a SARS-CoV-2-negative cohort.

OBJECTIVES: It remains unknown how inflammatory marker levels differ amongst individuals susceptible to coronavirus disease 2019 (COVID-19), prior to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the onset of the cytokine storm. We used genetic risk scores to model how susceptibility to severe COVID-19 correlates with baseline levels of 35 inflammatory markers, by testing their impact in a SARS-CoV-2-negative population cohort. Because of the established effects of age and body mass index on severe COVID-19 risk, we further considered how these variables interacted with genetic risk to affect inflammatory marker levels. METHODS: We accessed data on 406 SARS-CoV-2-negative individuals as part of a UK population study. Multiplex electrochemiluminescence methods were applied to blood serum, and 35 inflammatory markers were assayed. Corresponding genotype data, alongside results from a large genome-wide association study of severe COVID-19, allowed us to construct genetic risk scores and to test their impact on inflammatory protein levels. RESULTS: Our results revealed that a higher genetic risk for severe COVID-19 was associated with lower blood levels of interferon gamma (IFN-γ), vascular endothelial growth factor D (VEGF-D) and tumor necrosis factor alpha (TNF-α). Inflammatory profiles of those with high genetic risk increasingly diverge from the norm in association with age and obesity. CONCLUSION: Our results support the theory that individuals at risk of severe COVID-19 have a deficient innate immunity marked by reduced levels of inflammatory markers at baseline, including IFN-γ, VEGF-D and TNF-α. We hypothesise that a secondary overactive adaptive immune response may subsequently explain the high levels of cytokines observed in SARS-CoV-2-positive COVID-19 patients.

The behavioral, cellular and immune mediators of HIV-1 acquisition: New insights from population genetics.

Millions are exposed to the human immunodeficiency virus type 1 (HIV-1) every year, but not all acquire the virus, suggesting a potential role for host genetics in the moderation of HIV-1 acquisition. Here, we analyzed summary statistics from the largest genome-wide association study of HIV-1 acquisition to-date, consisting of 6,334 infected patients and 7,247 population controls, to advance our understanding of the genetic mechanisms implicated in this trait. We found that HIV-1 acquisition is polygenic and heritable, with SNP heritability estimates explaining 28-42% of the variance in this trait at a population level. Genetic correlations alongside UK Biobank data revealed associations with smoking, prospective memory and socioeconomic traits. Gene-level enrichment analysis identified EF-hand calcium binding domain 14 as a novel susceptibility gene for HIV-1 acquisition. We also observed that susceptibility variants for HIV-1 acquisition were significantly enriched for genes expressed in T-cells, but also in striatal and hippocampal neurons. Finally, we tested how polygenic risk scores for HIV-1 acquisition influence blood levels of 35 inflammatory markers in 406 HIV-1-negative individuals. We found that higher genetic risk for HIV-1 acquisition was associated with lower levels of C-C motif chemokine ligand 17. Our findings corroborate a complex model for HIV-1 acquisition, whereby susceptibility is partly heritable and moderated by specific behavioral, cellular and immunological parameters.

Inflammatory profiles of severe treatment-resistant depression.

BACKGROUND: Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients. METHODS: 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge. RESULTS: TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline. LIMITATIONS: The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results. CONCLUSIONS: However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.

Genetic Risk for Psychiatric Disorders and Telomere Length.

Background: Previous studies have revealed associations between psychiatric disorder diagnosis and shorter telomere length. Here, we attempt to discern whether genetic risk for psychiatric disorders, or use of pharmacological treatments (i.e., antidepressants), predict shorter telomere length and risk for aging-related disease in a United Kingdom population sample. Methods: DNA samples from blood were available from 351 participants who were recruited as part of the South East London Community Health (SELCoH) Study, and for which whole-genome genotype data was available. Leukocyte telomere length was characterized using quantitative polymerase chain reactions. Individualized polygenic risk scores for major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) were calculated using Psychiatric Genomics Consortium summary statistics. We subsequently performed linear models, to discern the impact polygenic risk for psychiatric disorders (an etiological risk factor) and antidepressant use (common pharmacological treatment) have on telomere length, whilst accounting for other lifestyle/health factors (e.g., BMI, smoking). Results: There were no significant associations between polygenic risk for any of the psychiatric disorders tested and telomere length (p > 0.05). Antidepressant use was significantly associated with shorter telomere length and this was independent from a depression diagnosis or current depression severity (p ≤ 0.01). Antidepressant use was also associated with a significantly higher risk of aging-related disease, which was independent from depression diagnosis (p ≤ 0.05). Conclusion: Genetic risk for psychiatric disorders is not associated with shorter telomere length. Further studies are now needed to prospectively characterize if antidepressant use increases risk for aging-related disease and telomere shortening, or whether people who age faster and have aging-related diseases are just more likely to be prescribed antidepressants.

Purpose in life and tobacco use among community-dwelling mothers of early adolescents.

OBJECTIVES: The rising prevalence of tobacco use and tobacco-attributable deaths among women is of worldwide concern. In particular, smoking prevention for mothers in early midlife is a significant international public health goal. A higher sense of purpose in life (PIL) is thought to reduce detrimental health behaviours. However, little is known about the association between a sense of PIL and tobacco use. This study investigates this association among community-dwelling mothers of early adolescents. DESIGN: This population-based cross-sectional study uses a self-reported questionnaire from the Tokyo Early Adolescence Survey, a large community-based survey conducted in Japan between 2012 and 2015. SETTING: Participants were randomly recruited from the resident registries of three municipalities in Tokyo, Japan. PARTICIPANTS: A total of 4478 children and their primary parents participated. Responses from 4063 mothers with no missing data were analysed (mean age=42.0 years (SD=4.2)). MEASURES: Participants' tobacco use, including the number of cigarettes smoked per day, was documented using a questionnaire. PIL was assessed using a Purpose in Life scale derived from Ryff's Psychological Well-Being Scale. RESULTS: Greater PIL was associated with a decreased likelihood of tobacco use, even when adjusted for confounders (OR=0.80, 95% CI 0.70 to 0.91). Multinomial logistic regression analyses revealed that PIL was inversely associated with tobacco consumption among mothers. These associations remained after controlling for psychological distress, socioeconomic factors and frequency of alcohol consumption among moderate to heavy smokers (OR=0.70, 95% CI 0.57 to 0.86), while attenuated among light smokers. CONCLUSIONS: Increasing PIL may be a valuable intervention for reducing tobacco use among women in early midlife. This study can contribute to our understanding of the psychology of smoking behaviour and shed light on the targeted intervention to reduce tobacco use among early midlife mothers.

Sociodemographic, lifestyle, and psychosocial determinants of hair cortisol in a South London community sample.

OBJECTIVE: Hypothalamic-pituitary-adrenal (HPA) measures are crucial for research into stress and stress-related disorders. Most HPA measures fluctuate depending on diurnal rhythms and state confounders. Hair cortisol concentrations (HCC) are less susceptible to such fluctuations, but less is known about trait-like confounders. Using a community sample, we tested the relationship between HCC and a range of variables including demographic variables, hair treatment, and medication, as well as psychosocial variables, namely childhood trauma, critical life events, and depressive symptoms. METHODS: Hair samples were collected from 144 individuals from the South East London Community Health (SELCoH) study. Childhood trauma, life events, and depressive symptoms were measured, together with age, sex, ethnicity, relationship status, educational attainment, employment status, occupational social class, hair washing frequency, hair treatments, season reflected in the hair sample, hazardous drinking, smoking, medication intake, and body mass index. Hair samples reflecting the past 3 months were collected and analysed using immunoassays. First, correlations (continuous variables) and simple linear regressions (dichotomous variables) were conducted to identify sociodemographic, hair-related, and lifestyle determinants of HCC. Next, multiple linear regressions were conducted to test the relationship between psychosocial variables and HCC when controlling for the identified confounders. RESULTS: Age (r=-0.17, p=0.050), White British ethnicity (ß=-0.19, p=0.023), heat-based treatments (ß=-0.22, p=0.010), and winter season (ß=-0.18, p=0.024) were associated with lower HCC, whereas summer season (ß=0.24, p=0.024), painkillers (ß=0.25, p=0.003), anxiolytics/antidepressants (ß=0.21, p=0.014), and hormonal contraceptives (ß=0.27, p=0.006) were associated with higher HCC. Controlling for these confounders, physical neglect during childhood (ß=-0.17, p=0.057), war-related experiences (ß=0.20, p=0.027), separation (ß=0.18, p=0.054), and being the victim of a serious crime (ß=-0.17, p=0.062) were linked with altered HCC. CONCLUSION: Our findings suggest that variation in HCC occurs according to sociodemographic, hair-related, and lifestyle variables, and that certain associations between stress and altered HCC can only be revealed when accounting for these confounders.

Medical and Welfare Officers beliefs about post-deployment screening for mental health disorders in the UK Armed Forces: a qualitative study.

BACKGROUND: This study aimed to examine currently serving United Kingdom (UK) military Medical and Welfare Officers views on the potential introduction of post-deployment screening for mental ill health. METHODS: Semi-structured interviews were conducted with 21 Medical and Welfare Officers. Interview transcripts were analysed using data-driven thematic analysis. RESULTS: Four themes were identified: positive views of screening; reliability of responses; impact on workload; and suggestions for implementation. Interviewees viewed the introduction of screening post-deployment as likely to increase awareness of mental health problems whilst also reporting that service personnel were likely to conceal their true mental health status by providing misleading responses to any screening tool. Concern over reliability of responses may provide one explanation for the reluctance of service personnel to seek help for problems, as they could feel they will not be taken seriously. Welfare Officers felt they would not have the knowledge or experience to respond to help-seeking. Although participants were concerned about potential impact on their personal workload, they indicated a desire to positively engage with the screening programme if research showed it was an effective tool to improve mental health care. CONCLUSIONS: Welfare and healthcare providers are well disposed towards a screening programme for mental health but highlight a few concerns in its implementation. In particular Welfare Officers appear to require more training in how to respond to mental ill health. Concerns about available funding and resources to respond to increased workload will need to be addressed should post-deployment screening for mental health be introduced in the UK military.

Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects.

BACKGROUND: There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. AIMS: To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. METHOD: Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. RESULTS: There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). CONCLUSIONS: Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors.

Comparisons of polydrug use at national and inner city levels in England: associations with demographic and socioeconomic factors.

PURPOSE: This study compares polydrug use in national and inner city samples to (1) examine patterns of use underlying different prevalence rates and (2) identify how inner city polydrug use needs targeting in ways not suggested by national research. METHODS: Latent class analyses on indicators of illicit drug use in the last year, hazardous alcohol use, and cigarette smoking were compared between the inner city 2008-2010 South East London Community Health study (n = 1698) and the nationally representative 2007 Adult Psychiatric Morbidity Survey in England (n = 7403). Multinomial logistic regressions then examined latent class solutions with demographic and socioeconomic factors. RESULTS: Both samples revealed three notably similar classes of polydrug users: a "high-drug" group using multiple substances; a "moderate-drug" group using cannabis, alcohol, and cigarettes; and a "low-drug" group reporting minimal alcohol and cigarette use. However, South East London Community Health reported lower risks of polydrug use for ethnic minorities but not for more educated participants. CONCLUSIONS: Despite higher polydrug use prevalence in the inner city, latent classes of polydrug users were similar between samples. Some demographic and socioeconomic factors differed between the samples, suggesting the need for inner city services to use both local and national data for policy planning.

Patients' experiences of living with and receiving treatment for fibromyalgia syndrome: a qualitative study.

BACKGROUND: Fibromyalgia syndrome (FMS) presents a challenge for patients and health care staff across many medical specialities. The aetiology is multi-dimensional, involving somatic, psychological and social factors. Patients' views were obtained to understand their experience of living with this long-term condition, using qualitative interviews. METHODS: 12 patients were recruited and stratified by age, gender and ethnicity from one rheumatology outpatient clinic, and a departmental held database of patients diagnosed with FMS. RESULTS: Patients' accounts of their experience of FMS resonated well with two central concepts: social identity and illness intrusiveness. These suggested three themes for the analytical framework: life before and after diagnosis (e.g. lack of information about FMS, invisibility of FMS); change in health identity (e.g. mental distress, impact on social life) and perceived quality of care (e.g. lack of contact with nurses, attitudes of specialists). The information provided from one male participant did not differ from the female patients, but black and ethnic community patients expressed a degree of suspicion towards the medication prescribed, and the attitudes displayed by some doctors, a finding that has not been previously reported amongst this patient group. Patients expected more consultation time and effective treatment than they received. Subjective experiences and objective physical and emotional changes were non-overlapping. Patients' accounts revealed that their physical, mental and social health was compromised, at times overwhelming and affected their identity. CONCLUSION: FMS is a condition that intrudes upon many aspects of patients' lives and is little understood. At the same time, it is a syndrome that evokes uneasiness in health care staff (as current diagnostic criteria are not well supported by objective markers of physiological or biochemical nature, and indeed because of doubt about the existence of the condition) and places great demands on resources in clinical practice. Greater attention needs to be paid to the links between the explanatory models of patients and staff, and most important, to the interrelationship between the complex physical, psychological and social needs of patients with FMS. Taking a less medical but more holistic approach when drawing up new diagnostic criteria for FMS might match better individuals' somatic and psycho-social symptom profile and may result in more effective treatment.