Depressive symptoms and neuroticism-related traits are the main factors associated with wellbeing independent of the history of lifetime depression in the UK Biobank.

BACKGROUND: Wellbeing has a fundamental role in determining life expectancy and major depressive disorder (MDD) is one of the main modulating factors of wellbeing. This study evaluated the modulators of wellbeing in individuals with lifetime recurrent MDD (RMDD), single-episode MDD (SMDD) and no MDD in the UK Biobank. METHODS: Scores of happiness, meaningful life and satisfaction about functioning were condensed in a functioning-wellbeing score (FWS). We evaluated depression and anxiety characteristics, neuroticism-related traits, physical diseases, lifestyle and polygenic risk scores (PRSs) of psychiatric disorders. Other than individual predictors, we estimated the cumulative contribution to FWS of each group of predictors. We tested the indirect role of neuroticism on FWS through the modulation of depression manifestations using a mediation analysis. RESULTS: We identified 47 966, 21 117 and 207 423 individuals with lifetime RMDD, SMDD and no MDD, respectively. Depression symptoms and personality showed the largest impact on FWS (variance explained ~20%), particularly self-harm, worthlessness feelings during the worst depression, chronic depression, loneliness and neuroticism. Personality played a stronger role in SMDD. Anxiety characteristics showed a higher effect in SMDD and no MDD groups. Neuroticism played indirect effects through specific depressive symptoms that modulated FWS. Physical diseases and lifestyle explained only 4-5% of FWS variance. The PRS of MDD showed the largest effect on FWS compared to other PRSs. CONCLUSIONS: This was the first study to comprehensively evaluate the predictors of wellbeing in relation to the history of MDD. The identified variables are important to identify individuals at risk and promote wellbeing.

Brain stimulation treatment for bipolar disorder.

AIMS: Bipolar disorders are clinically complex, chronic and recurrent disorders. Few treatment options are effective across hypomanic, manic, depressive and mixed states and as continuation or maintenance treatment after initial symptom remission. The aim of this review was to provide an up-to-date overview of research on the efficacy, tolerability and cognitive effects of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), deep brain stimulation (DBS) and vagus nerve stimulation (VNS). METHODS: References included in this review were identified through multiple searches of the Embase, PubMed/MEDLINE and APA PsycINFO electronic databases for articles published from inception until February 2022. Published reviews, meta-analyses, randomised controlled trials and recent studies were prioritised to provide a comprehensive and up-to-date overview of research on brain stimulation in patients with bipolar disorders. RESULTS: The evidence base for brain stimulation as an add-on or alternative to pharmacological and psychological treatments in patients with bipolar disorders is limited but rapidly expanding. Brain stimulation treatments represent an opportunity to treat all bipolar disorder states, including cognitive dysfunction during euthymic periods. CONCLUSION: Whilst findings to date have been encouraging, larger randomised controlled trials with long-term follow-up are needed to clarify important questions regarding treatment efficacy and tolerability, the frequency of treatment-emergent affective switches and effects on cognitive function.

The Cost-Effectiveness of Financial Incentives to Achieve Heroin Abstinence in Individuals With Heroin Use Disorder Starting New Treatment Episodes: A Cluster Randomized Trial-Based Economic Evaluation.

OBJECTIVES: Cost-effectiveness analysis of two 12-week contingency management (CM) schedules targeting heroin abstinence or attendance at weekly keyworker appointments for opioid agonist treatment compared with treatment as usual (TAU). METHODS: A cost-effectiveness analysis was conducted alongside a cluster randomized trial of 552 patients from 34 clusters (drug treatment clinics) randomly allocated 1:1:1 to opioid agonist treatment plus weekly keyworker appointments with (1) CM targeted at heroin abstinence (CM abstinence), (2) CM targeted at on-time attendance at weekly appointments (CM attendance), or (3) no CM (TAU). The primary cost-effectiveness analysis at 24 weeks after randomization took a societal cost perspective with effects measured in heroin-negative urine samples. RESULTS: At 24 weeks, mean differences in weekly heroin-negative urine results compared with TAU were 0.252 (95% confidence interval [CI] -0.397 to 0.901) for CM abstinence and 0.089 (95% CI -0.223 to 0.402) for CM attendance. Mean differences in costs were £2562 (95% CI £32-£5092) for CM abstinence and £317 (95% CI -£882 to £1518) for CM attendance. Incremental cost-effectiveness ratios were £10 167 per additional heroin-free urine for CM abstinence and £3562 for CM attendance with low probabilities of cost-effectiveness of 3.5% and 36%, respectively. Results were sensitive to timing of follow-up for CM attendance, which dominated TAU (better outcomes, lower costs) at 12 weeks, with an 88.4% probability of being cost-effective. Probability of cost-effectiveness remained low for CM abstinence (8.6%). CONCLUSIONS: Financial incentives targeted toward heroin abstinence and treatment attendance were not cost-effective over the 24-week follow-up. Nevertheless, CM attendance was cost-effective over the treatment period (12 weeks), when participants were receiving keyworker appointments and incentives.

Frailty in individuals with depression, bipolar disorder and anxiety disorders: longitudinal analyses of all-cause mortality.

BACKGROUND: Frailty is a medical syndrome that is strongly associated with mortality risk and an emerging global health burden. Mental disorders are associated with reduced life expectancy and elevated levels of frailty. In this study, we examined the mortality risk associated with frailty in individuals with a lifetime history of mental disorders compared to individuals without a history of mental disorders. METHODS: The UK Biobank study recruited > 500,000 adults, aged 37-73, between 2006 and 2010. We derived the two most common albeit distinctive measures of frailty, the frailty phenotype and the frailty index. Individuals with lifetime depression, bipolar disorder or anxiety disorders were identified from multiple data sources. The primary outcome was all-cause mortality. We have also examined differences in frailty, separately by sex and age. RESULTS: Analyses included up to 297,380 middle-aged and older adults with a median follow-up of 12.19 (interquartile range = 1.31) years, yielding 3,516,706 person-years of follow-up. We observed higher levels of frailty in individuals with mental disorders for both frailty measures. Standardised mean differences in the frailty index ranged from 0.66 (95% confidence interval [CI] 0.65-0.67) in individuals with anxiety disorders to 0.94 (95% CI 0.90-0.97) in individuals with bipolar disorder, compared to people without mental disorders. For key comparisons, individuals with a mental disorder had greater all-cause mortality hazards than the comparison group without mental disorders. The highest hazard ratio (3.65, 95% CI 2.40-5.54) was observed among individuals with bipolar disorder and frailty, relative to non-frail individuals without mental disorders. CONCLUSIONS: Our findings highlight elevated levels of frailty across three common mental disorders. Frailty and mental disorders represent potentially modifiable targets for prevention and treatment to improve population health and life expectancy, especially where both conditions coexist.

Anxiety disorders and age-related changes in physiology.

BACKGROUND: Anxiety disorders are leading contributors to the global disease burden, highly prevalent across the lifespan and associated with substantially increased morbidity and early mortality. AIMS: The aim of this study was to examine age-related changes across a wide range of physiological measures in middle-aged and older adults with a lifetime history of anxiety disorders compared with healthy controls. METHOD: The UK Biobank study recruited >500 000 adults, aged 37-73, between 2006 and 2010. We used generalised additive models to estimate non-linear associations between age and hand-grip strength, cardiovascular function, body composition, lung function and heel bone mineral density in a case group and in a control group. RESULTS: The main data-set included 332 078 adults (mean age 56.37 years; 52.65% females). In both sexes, individuals with anxiety disorders had a lower hand-grip strength and lower blood pressure, whereas their pulse rate and body composition measures were higher than in the healthy control group. Case-control group differences were larger when considering individuals with chronic and/or severe anxiety disorders, and differences in body composition were modulated by depression comorbidity status. Differences in age-related physiological changes between females in the anxiety disorder case group and healthy controls were most evident for blood pressure, pulse rate and body composition, whereas this was the case in males for hand-grip strength, blood pressure and body composition. Most differences in physiological measures between the case and control groups decreased with increasing age. CONCLUSIONS: Findings in individuals with a lifetime history of anxiety disorders differed from a healthy control group across multiple physiological measures, with some evidence of case-control group differences by age. The differences observed varied by chronicity/severity and depression comorbidity.

Personal radiofrequency electromagnetic field exposure of adolescents in the Greater London area in the SCAMP cohort and the association with restrictions on permitted use of mobile communication technologies at school and at home.

Personal measurements of radiofrequency electromagnetic fields (RF-EMF) have been used in several studies to characterise personal exposure in daily life, but such data are limitedly available for adolescents, and not yet for the United Kingdom (UK). In this study, we aimed to characterise personal exposure to RF-EMF in adolescents and to study the association between exposure and rules applied at school and at home to restrict wireless communication use, likely implemented to reduce other effects of mobile technology (e.g. distraction). We measured exposure to RF-EMF for 16 common frequency bands (87.5 MHz-3.5 GHz), using portable measurement devices (ExpoM-RF), in a subsample of adolescents participating in the cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP) from Greater London (UK) (n = 188). School and home rules were assessed by questionnaire and concerned the school's availability of WiFi and mobile phone policy, and parental restrictions on permitted mobile phone use. Adolescents recorded their activities in real time using a diary app on a study smartphone, while characterizing their personal RF-EMF exposure in daily life, during different activities and times of the day. Data analysis was done for 148 adolescents from 29 schools who recorded RF-EMF data for a median duration of 47 h. The majority (74%) of adolescents spent part of their time at school during the measurement period. Median total RF-EMF exposure was 40 µW/m2 at home, 94 µW/m2 at school, and 100 µW/m2 overall. In general, restrictions at school or at home made little difference for adolescents' measured exposure to RF-EMF, except for uplink exposure from mobile phones while at school, which was found to be significantly lower for adolescents attending schools not permitting phone use at all, compared to adolescents attending schools allowing mobile phone use during breaks. This difference was not statistically significant for total personal exposure. Total exposure to RF-EMF in adolescents living in Greater London tended to be higher compared to exposure levels reported in other European countries. This study suggests that school policies and parental restrictions are not associated with a lower RF-EMF exposure in adolescents.

Exploring health in the UK Biobank: associations with sociodemographic characteristics, psychosocial factors, lifestyle and environmental exposures.

BACKGROUND: A greater understanding of the factors that are associated with favourable health may help increase longevity and healthy life expectancy. We examined sociodemographic, psychosocial, lifestyle and environmental exposures associated with multiple health indicators. METHODS: UK Biobank recruited > 500,000 participants, aged 37-73, between 2006 and 2010. Health indicators examined were 81 cancer and 443 non-cancer illnesses used to classify participants' health status; long-standing illness; and self-rated health. Exposures were sociodemographic (age, sex, ethnicity, education, income and deprivation), psychosocial (loneliness and social isolation), lifestyle (smoking, alcohol intake, sleep duration, BMI, physical activity and stair climbing) and environmental (air pollution, noise and residential greenspace) factors. Associations were estimated using logistic and ordinal logistic regression. RESULTS: In total, 307,378 participants (mean age = 56.1 years [SD = 8.07], 51.9% female) were selected for cross-sectional analyses. Low income, being male, neighbourhood deprivation, loneliness, social isolation, short or long sleep duration, low or high BMI and smoking were associated with poor health. Walking, vigorous-intensity physical activity and more frequent alcohol intake were associated with good health. There was some evidence that airborne pollutants (PM2.5, PM10 and NO2) and noise (Lden) were associated with poor health, though findings were not consistent across all models. CONCLUSIONS: Our findings highlight the multifactorial nature of health, the importance of non-medical factors, such as loneliness, healthy lifestyle behaviours and weight management, and the need to examine efforts to improve the health outcomes of individuals on low incomes.

Is tDCS a potential first line treatment for major depression?

Transcranial direct current stimulation (tDCS) is a novel treatment option for major depression which could be provided as a first-line treatment. tDCS is a non-invasive form of transcranial stimulation which changes cortical tissue excitability by applying a weak (0.5-2 mA) direct current via scalp electrodes. Anodal and cathodal stimulation leads to depolarisation and hyperpolarisation, respectively, and cumulative effects are observed with repeated sessions. The montage in depression most often involves anodal stimulation to the left dorsolateral prefrontal cortex. Rates of clinical response, remission, and improvements in depressive symptoms following a course of active tDCS are greater in comparison to a course of placebo sham-controlled tDCS. In particular, the largest treatment effects are evident in first episode and recurrent major depression, while minimal effects have been observed in treatment-resistant depression. The proposed mechanism is neuroplasticity at the cellular and molecular level. Alterations in neural responses have been found at the stimulation site as well as subcortically in prefrontal-amygdala connectivity. A possible mediating effect could be cognitive control in emotion dysregulation. Additional beneficial effects on cognitive impairments have been reported, which would address an important unmet need. The tDCS device is portable and can be used at home. Clinical trials are required to establish the efficacy, feasibility and acceptability of home-based tDCS treatment and mechanisms.

Repetitive transcranial magnetic stimulation in non-treatment-resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) has been investigated as treatment for major depressive episodes since the early 1990s. Using data from a recent meta-analysis, we show that most patients included in randomised trials display relatively high degrees of treatment resistance. This might have unfavourably biased the clinical reputation of rTMS.Declaration of interestsM.K. has received a lecture fee from Innomed Medizintechnik in 2017 and 2018.

The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality.

Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (ß = - 0.022, 95% CI - 0.081 to 0.037, p = 0.47), the total duration of use (ß = - 0.005, 95% CI - 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (ß = - 0.018, 95% CI - 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.

Genome-wide association studies of coffee intake in UK/US participants of European ancestry uncover cohort-specific genetic associations.

Coffee is one of the most widely consumed beverages. We performed a genome-wide association study (GWAS) of coffee intake in US-based 23andMe participants (N = 130,153) and identified 7 significant loci, with many replicating in three multi-ancestral cohorts. We examined genetic correlations and performed a phenome-wide association study across hundreds of biomarkers, health, and lifestyle traits, then compared our results to the largest available GWAS of coffee intake from the UK Biobank (UKB; N = 334,659). We observed consistent positive genetic correlations with substance use and obesity in both cohorts. Other genetic correlations were discrepant, including positive genetic correlations between coffee intake and psychiatric illnesses, pain, and gastrointestinal traits in 23andMe that were absent or negative in the UKB, and genetic correlations with cognition that were negative in 23andMe but positive in the UKB. Phenome-wide association study using polygenic scores of coffee intake derived from 23andMe or UKB summary statistics also revealed consistent associations with increased odds of obesity- and red blood cell-related traits, but all other associations were cohort-specific. Our study shows that the genetics of coffee intake associate with substance use and obesity across cohorts, but also that GWAS performed in different populations could capture cultural differences in the relationship between behavior and genetics.

Telomere Length Associations With Clinical Diagnosis, Age, and Polygenic Risk Scores for Anxiety Disorder, Depression, and Bipolar Disorder.

Background: Accelerated biological aging might contribute to the lower life expectancy of individuals with mental disorders. The aim of this study was to characterize telomere length, a biological hallmark of aging, in individuals with mental disorders. Methods: The UK Biobank is a multicenter community-based observational study that recruited >500,000 middle-aged and older adults. Average leukocyte telomere length (telomere repeat copy number/single-copy gene ratio) was measured using quantitative polymerase chain reaction. Polygenic risk scores (PRSs) were calculated for individuals of European ancestry. We estimated differences in telomere length between individuals with anxiety disorder, depression, or bipolar disorder and people without mental disorders and examined associations with psychotropic medication use, age, and PRSs for these 3 disorders. Results: The analyses included up to 308,725 participants. Individuals with depression had shorter telomeres than people without mental disorders (ß = -0.011, 95% CI, -0.019 to -0.004, Bonferroni-corrected p = .027). Associations between bipolar disorder and telomere length differed by lithium use. There was limited evidence that individuals with an anxiety disorder had shorter telomeres. There was no evidence that associations between age and telomere length differed between individuals with and without these disorders. PRSs for depression, but not anxiety disorder or bipolar disorder, were associated with shorter telomeres (ß = -0.006, 95% CI, -0.010 to -0.003, Bonferroni-corrected p = .001). Conclusions: Differences in telomere length were observed primarily for individuals with depression or bipolar disorder and in individuals with a higher PRS for depression. There was no evidence that the association between age and telomere length differed between individuals with and without an anxiety disorder, depression, or bipolar disorder.

Exploring the concept of psychological frailty in older adults: a systematic scoping review.

OBJECTIVES: We reviewed the existing definitions of psychological frailty and provided a comprehensive overview of the concept and associated measurements. STUDY DESIGN AND SETTING: We followed the PRISMA guidelines for scoping reviews and the Joanna Briggs Institute Manual for Evidence Synthesis. The eligibility criteria for including studies were developed based on the participants-concept-context framework. We searched the Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, Web of Science and PsycINFO databases, and other sources for relevant studies published between January 2003 and March 2022. RESULTS: The final scoping review included 58 studies. Of these, 40 defined psychological frailty, seven provided a novel definition, and 11 focused on the components defining psychological frailty. We proposed four groups of components to better characterize psychological frailty: mood, cognitive, other mental health, and fatigue-related problems. We identified 28 measuring tools across studies, and the Tilburg Frailty Indicator was the most frequently used (46.6%). CONCLUSION: Psychological frailty is a complex concept whose definition seems to lack consensus. It could include both psychological and physical features. Depression and anxiety are commonly used to define it. This scoping review outlined future research directions for refining the concept of psychological frailty.

The efficacy and acceptability of psychological interventions for adult PTSD: A network and pairwise meta-analysis of randomized controlled trials.

OBJECTIVE: A comprehensive quantitative summary of the efficacy and acceptability of psychological interventions (PIs) for adult posttraumatic stress disorder (PTSD) is lacking. METHOD: We conducted a systematic literature search to identify randomized controlled trials (RCTs) examining the efficacy and acceptability (all-cause dropout) of psychological interventions (i.e., trauma-focused cognitive behavior therapy [TF-CBT], eye movement desensitization and reprocessing [EMDR], other trauma-focused interventions and non-trauma-focused interventions). RESULTS: One hundred fifty-seven RCTs were included comprising 11,565 patients. Most research (64% of RCTs) accumulated for TF-CBT. In network meta-analyses, all therapies were effective when compared to control conditions. Interventions did not differ significantly in their efficacy. Yet, TF-CBT yielded higher short- (g = 0.17, 95% CI [0.03-0.31], number of comparisons kes = 190), mid- (i.e., ≤5 months posttreatment, g = 0.23, 95% CI [0.06-0.40], kes = 73) and long-term efficacy (i.e., >5 months posttreatment, g = 0.20, 95% CI [0.04-0.35], kes = 41) than non-trauma-focused interventions. There was some evidence of network inconsistencies, and heterogeneity in outcomes was large. In pairwise meta-analysis, slightly more patients dropped out from TF-CBT than non-trauma-focused interventions (RR = 1.36; 95% CI [1.08-1.70], kes = 22). Other than that, interventions did not differ in their acceptability. CONCLUSIONS: Interventions with and without trauma focus are effective and acceptable in the treatment of PTSD. While TF-CBT yields the highest efficacy, slightly more patients discontinued TF-CBT than non-trauma-focused interventions. Altogether, the present results align with results of most previous quantitative reviews. Yet, results need to be interpreted with caution in light of some network inconsistencies and high heterogeneity in outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Genome-Wide Association Studies of Coffee Intake in UK/US Participants of European Ancestry Uncover Gene-Cohort Influences.

Coffee is one of the most widely consumed beverages. We performed a genome-wide association study (GWAS) of coffee intake in US-based 23andMe participants (N=130,153) and identified 7 significant loci, with many replicating in three multi-ancestral cohorts. We examined genetic correlations and performed a phenome-wide association study across thousands of biomarkers and health and lifestyle traits, then compared our results to the largest available GWAS of coffee intake from UK Biobank (UKB; N=334,659). The results of these two GWAS were highly discrepant. We observed positive genetic correlations between coffee intake and psychiatric illnesses, pain, and gastrointestinal traits in 23andMe that were absent or negative in UKB. Genetic correlations with cognition were negative in 23andMe but positive in UKB. The only consistent observations were positive genetic correlations with substance use and obesity. Our study shows that GWAS in different cohorts could capture cultural differences in the relationship between behavior and genetics.

Cross-classification between self-rated health and health status: longitudinal analyses of all-cause mortality and leading causes of death in the UK.

Risk stratification is an important public health priority that is central to clinical decision making and resource allocation. The aim of this study was to examine how different combinations of self-rated and objective health status predict all-cause mortality and leading causes of death in the UK. The UK Biobank study recruited > 500,000 participants between 2006 and 2010. Self-rated health was assessed using a single-item question and health status was derived from medical history, including data on 81 cancer and 443 non-cancer illnesses. Analyses included > 370,000 middle-aged and older adults with a median follow-up of 11.75 (IQR = 1.4) years, yielding 4,320,270 person-years of follow-up. Compared to individuals with excellent self-rated health and favourable health status, individuals with other combinations of self-rated and objective health status had a greater mortality risk, with hazard ratios ranging from HR = 1.22 (95% CI 1.15-1.29, PBonf. < 0.001) for individuals with good self-rated health and favourable health status to HR = 7.14 (95% CI 6.70-7.60, PBonf. < 0.001) for individuals with poor self-rated health and unfavourable health status. Our findings highlight that self-rated health captures additional health-related information and should be more widely assessed. The cross-classification between self-rated health and health status represents a straightforward metric for risk stratification, with applications to population health, clinical decision making and resource allocation.

Age-related changes in physiology in individuals with bipolar disorder.

BACKGROUND: Individuals with bipolar disorder have a reduced life expectancy and may experience accelerated biological ageing. In individuals with bipolar disorder and healthy controls, we examined differences in age-related changes in physiology. METHODS: UK Biobank recruited more than 500,000 participants, aged 37-73, between 2006 and 2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and heel bone mineral density. RESULTS: The main dataset included 271,118 adults (mean age = 56.04 years; 49.60% females). We found statistically significant differences between cases and controls for grip strength, blood pressure, pulse rate and body composition, with standardised mean differences of up to -0.24 (95% CI -0.28 to -0.19). Evidence of differences in lung function, heel bone mineral density or arterial stiffness was limited. Case-control differences were most evident for age-related changes in cardiovascular function (both sexes) and body composition (females). Differences did not uniformly narrow or widen with age and differed by sex. For example, the difference in systolic blood pressure between male cases and controls was -1.3 mmHg at age 50 and widened to -4.7 mmHg at age 65. Diastolic blood pressure in female cases was 1.2 mmHg higher at age 40 and -1.2 mmHg lower at age 65. LIMITATIONS: Analyses did not distinguish between bipolar disorder subtypes. Results may not generalise to other age groups. CONCLUSIONS: Differences between bipolar disorder cases and controls were most evident for cardiovascular and body composition measures. Targeted screening for cardiovascular and metabolic health in middle age is warranted to potentially mitigate excess mortality.

Stratification of individuals with lifetime depression and low wellbeing in the UK Biobank.

BACKGROUND: Previous studies stratified patients with major depressive disorder (MDD) based on their clinical characteristics. This study used this approach in individuals with lifetime MDD who reported low wellbeing, a group of high clinical relevance. METHODS: We selected participants in the UK Biobank (UKB) with lifetime MDD and a wellbeing score in the lowest 25 %. A wellbeing score was previously created considering happiness, belief that own life is meaningful, health satisfaction and functioning in relevant areas. In the selected group, we applied latent class analysis using mood-spectrum symptoms and personality traits as input variables, then we compared the clinical-demographic and genetic (polygenic risk scores, PRSs) characteristics of the identified classes. RESULTS: A total of 13,896 individuals were included and a model with five classes showed the best performance. The most common class (31.25 %) was characterised by periods of irritable mood and trait irritability with high neuroticism. A rarer class (16.49 %) showed depressive-manic mood fluctuations and risk-taking personality, higher percentage of males, atypical depressive symptoms, lower socio-economic status, higher PRS for attention-deficit hyperactivity disorder and lower PRS for education. The second most common class (29.79 %) showed worry as main personality trait with low risk of manic/irritable manifestations. The remaining classes showed an anxious-irritable personality profile and a purely depressive profile (4.92 % and 17.55 %, respectively). LIMITATIONS: Our results may reflect the characteristics of UKB participants. CONCLUSIONS: Subthreshold manic/irritable mood fluctuations and personality traits irritability and neuroticism may distinguish the most common groups with poor wellbeing in lifetime MDD.

Lifetime depression and age-related changes in body composition, cardiovascular function, grip strength and lung function: sex-specific analyses in the UK Biobank.

Individuals with depression, on average, die prematurely, have high levels of physical comorbidities and may experience accelerated biological ageing. A greater understanding of age-related changes in physiology could provide novel biological insights that may help inform strategies to mitigate excess mortality in depression. We used generalised additive models to examine age-related changes in 15 cardiovascular, body composition, grip strength and lung function measures, comparing males and females with a lifetime history of depression to healthy controls. The main dataset included 342,393 adults (mean age = 55.87 years, SD = 8.09; 52.61% females). We found statistically significant case-control differences for most physiological measures. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in depression. These differences did not uniformly narrow or widen with age and differed by sex. For example, BMI in female cases was 1.1 kg/m2 higher at age 40 and this difference narrowed to 0.4 kg/m2 at age 70. In males, systolic blood pressure was 1 mmHg lower in depression cases at age 45 and this difference widened to 2.5 mmHg at age 65. These findings suggest that targeted screening for physiological function in middle-aged and older adults with depression is warranted to potentially mitigate excess mortality.