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

BACKGROUND: Chronic physical illness increases the risk of subsequent depressive symptoms, but we know little about the mechanisms underlying this association that interventions can target. We investigated whether loneliness might explain associations between chronic illness and subsequent depressive symptoms. METHODS: We used English Longitudinal Study of Ageing data, a prospective cohort of adults over 50. Our exposure was chronic illnesses (wave two) including arthritis, cancer, diabetes, cardiovascular disease, stroke, and chronic obstructive pulmonary disease. Loneliness scores were a mediator on the short University of California, Los Angeles Loneliness Scale at wave three. Depressive symptom scores (outcome) were measured using the Centre for Epidemiologic Studies Depression Scale (wave four). We examined associations of chronic physical illness with loneliness and depressive symptoms in univariable and multivariable regression models. RESULTS: Fully-adjusted models included 2436 participants with the depression outcome and 2052 participants with the loneliness outcome. Chronic physical illness was associated with 21 % (incident rate ratio = 1.21, 95%CI = 1.03-1.42) higher depression scores at follow-up. We found no evidence of an association between chronic physical illness and loneliness and therefore did not proceed to analyses of mediation. LIMITATIONS: More prevalent chronic illnesses could have driven our results, such as cardiovascular disease. CONCLUSIONS: Chronic physical illnesses increase the risk of depressive symptoms in older adults. However, we did not find any that chronic physical illnesses were associated with an increased risk of subsequent loneliness. Therefore, interventions targeting loneliness to reduce depression in older adults with chronic physical illness may be insufficient.

Device-measured sedentary behaviour and anxiety symptoms during adolescence: a 6-year prospective cohort study.

BACKGROUND: Sedentary behaviour is potentially a modifiable risk factor for anxiety disorders, a major source of global disability that typically starts during adolescence. This is the first prospective study of associations between repeated, device-based measures of sedentary behaviour and anxiety symptoms in adolescents. METHODS: A UK cohort with 4257 adolescents aged 12 at baseline (56% female). Main exposures were sedentary behaviour and physical activity measured using accelerometers for 7-days at ages 12, 14, and 16. Primary outcome was anxiety symptom scores at age 18 from a Clinical Interview Schedule-Revised. We used adjusted negative binomial regression and iso-temporal substitution methods to analyse the data. RESULTS: We found a positive association between sedentary behaviour at ages 12, 14, and 16, with anxiety symptoms at age 18, independent of total physical activity volume. Theoretically replacing an hour of daily sedentary behaviour for light activity at ages 12, 14, and 16, was associated with lower anxiety symptoms by age 18 by 15.9% (95% CI 8.7-22.4), 12.1% (95% CI 3.4-20.1), and 14.7% (95% CI 4-24.2), respectively. Whereas, theoretically replacing an hour of sedentary behaviour with moderate-to-vigorous physical activity was not associated with differences in anxiety symptoms. These results were robust to a series of sensitivity analyses. CONCLUSION: Sedentary behaviour is a possible risk factor for increasing anxiety symptoms during adolescence, independent of total physical activity volume. Instead of focusing on moderate-to-vigorous activity, replacing daily sedentary behaviour with light activity during adolescence could be a more suitable method of reducing future anxiety symptoms.

Impact of replacing sedentary behaviour with other movement behaviours on depression and anxiety symptoms: a prospective cohort study in the UK Biobank.

BACKGROUND: Sedentary behaviour is potentially a modifiable risk factor for depression and anxiety disorders, but findings have been inconsistent. To assess the associations of sedentary behaviour with depression and anxiety symptoms and estimate the impact of replacing daily time spent in sedentary behaviours with sleep, light, or moderate to vigorous physical activity, using compositional data analysis methods. METHODS: We conducted a prospective cohort study in 60,235 UK Biobank participants (mean age: 56; 56% female). Exposure was baseline daily movement behaviours (accelerometer-assessed sedentary behaviour and physical activity, and self-reported total sleep). Outcomes were depression and anxiety symptoms (Patient Health Questionnaire-9 and Generalised Anxiety Disorders-7) at follow-up. RESULTS: Replacing 60 min of sedentary behaviour with light activity, moderate-to-vigorous activity, and sleep was associated with lower depression symptom scores by 1.3% (95% CI, 0.4-2.1%), 12.5% (95% CI, 11.4-13.5%), and 7.6% (95% CI, 6.9-8.4%), and lower odds of possible depression by 0.95 (95% CI, 0.94-0.96), 0.75 (95% CI, 0.74-0.76), and 0.90 (95% CI, 0.90-0.91) at follow-up. Replacing 60 min of sedentary behaviour with moderate-to-vigorous activity and sleep was associated with lower anxiety symptom scores by 6.6% (95% CI, 5.5-7.6%) and 4.5% (95% CI, 3.7-5.2%), and lower odds of meeting the threshold for a possible anxiety disorder by 0.90 (95% CI, 0.89-0.90) and 0.97 (95%CI, 0.96-0.97) at follow-up. However, replacing 60 min of sedentary behaviour with light activity was associated with higher anxiety symptom scores by 4.5% (95% CI, 3.7-5.3%) and higher odds of a possible anxiety disorder by 1.07 (95% CI, 1.06-1.08). CONCLUSIONS: Sedentary behaviour is a risk factor for increased depression and anxiety symptoms in adults. Replacing sedentary behaviour with moderate-to-vigorous activity may reduce mental health risks, but more work is necessary to clarify the role of light activity.

Prospective relationships of adolescents' screen-based sedentary behaviour with depressive symptoms: the Millennium Cohort Study.

BACKGROUND: Frequent use of screen-based devices could be a modifiable risk factor for adolescent depression, but findings have been inconsistent and mostly from cross-sectional studies. We examined prospective associations of video gaming, social media, and internet use with depressive symptoms in adolescents. METHODS: A total of 11 341 adolescents from the Millennium Cohort Study, a representative, UK population-based. The main outcome was depressive symptoms from a Moods and Feelings Questionnaire (age 14). Exposures were frequency of video game, social media, and internet use (age 11). Physical activity (effect modifier) was measured by self-report. RESULTS: The fully adjusted models indicated that boys playing video games most days, at least once a week, and at least once a month at age 11 had lower depression scores at age 14 by 24.2% (IRR = 0.77, 95% CI 0.66-0.91), 25.1% (IRR = 0.75, 95% CI 0.62-0.90), and 31.2% (IRR = 0.69, 95% CI 0.57-0.83), compared with playing less than once a month/never. In girls, compared with less than once a month/never, using social media most days at age 11 was associated with 13% higher depression scores at age 14 (IRR = 1.13, 95% CI 1.05-1.22). We found some evidence of associations between using the internet most days and depressive symptoms compared with less than once a month/never in boys (IRR = 0.86, 95% CI 0.75-1.00). More frequent video game use was consistently associated with fewer depressive symptoms in boys with low physical activity, but not in those with high physical activity. CONCLUSIONS: Different types of screen-time may have contrasting associations with depressive symptoms during adolescence. Initiatives to address adolescents' screen-time may require targeted approaches.

Physical multimorbidity and sedentary behavior in older adults: Findings from the Irish longitudinal study on ageing (TILDA).

BACKGROUND: Physical multimorbidity, defined as the presence of two or more chronic physical conditions, is widespread and reduces life expectancy and quality of life in older adults. Sedentary behavior (SB) is increasingly identified as a risk factor for a range of chronic physical conditions, independent of physical activity. OBJECTIVES: To investigate associations between physical multimorbidity and SB in older adults. STUDY DESIGN: We used cross-sectional data from a population-based sample of 6903 adults aged ≥50 years who participated in the Irish Longitudinal Study on Ageing (TILDA) in 2009-2011. We conducted multivariable linear and logistic regression analyses to assess associations between multimorbidity and SB. MAIN OUTCOME MEASURES: Self-reported minutes/day of SB and high SB (≥ 8 h/day). RESULTS: We found that most of the 14 individual chronic physical conditions included here were associated with greater SB. Those with stroke (OR = 2.63, 95 % CI = 1.69, 4.10) and cirrhosis (OR = 2.53, 95 %CI = 1.19, 5.41) were the most likely to be classified with high SB. Time spent in SB and the prevalence of high SB increased linearly with number of chronic conditions. Multivariable regression models adjusting for sociodemographic and psychological factors, disability, social network, and physical activity showed that, compared with people with none, those with ≥4 chronic physical conditions had 1.45 times greater odds (OR = 1.45, 95 % CI = 1.09, 1.93) of high SB and higher mean minutes/day of SB (ß = 21.37, 95 % CI = 5.53, 37.20). CONCLUSIONS: Our results suggest that physical multimorbidity is associated with SB and highlight the need for prospective research to examine the directionality and mechanisms of these associations.

The association between cardiorespiratory fitness and the incidence of common mental health disorders: A systematic review and meta-analysis.

BACKGROUND: Physical activity is associated with a lower incidence of common mental health disorder, but less is known about the impact of cardiorespiratory fitness (CRF). METHODS: In this review, we systematically evaluated the relationship between CRF and the incidence of common mental health disorders in prospective cohort studies. We systematically searched six major electronic databases from inception to 23rd of May 2019. We assessed study quality using the Newcastle-Ottawa scale. RESULTS: We were able to pool the hazard ratios (HRs) and 95% confidence intervals (CIs) of four studies including at least 27,733,154 person-years of data. We found that low CRF (HR = 1.47, [95% CI 1.23 - 1.76] p < 0.001 I2 = 85.1) and medium CRF (HR = 1.23, [95% CI 1.09 - 1.38] p < 0.001 I2 = 87.20) CRF are associated with a 47% and 23% greater risk of a common mental health disorders respectively, compared with high CRF. We found evidence to suggest a dose-response relationship between CRF and the risk of common mental health disorders. LIMITATIONS: We were only able to identify a small number of eligible studies from our search and heterogeneity was substantial in the subsequent meta-analysis. CONCLUSIONS: Our findings indicate that there is a longitudinal association between CRF levels and the risk of a common mental health disorder. CRF levels could be useful for identifying and preventing common mental health disorders at a population-level.

A systematic review and meta-analysis of clinical predictors of lithium response in bipolar disorder.

OBJECTIVE: To determine clinical predictors of lithium response in bipolar disorder. METHODS: Systematic review of studies examining clinical predictors of lithium response was conducted. Meta-analyses were performed when ≥2 studies examined the same potential predictor. RESULTS: A total of 71 studies, including over 12 000 patients, identified six predictors of good response: mania-depression-interval sequence [odds ratio (OR): 4.27; 95% CI: 2.61, 6.97; P < 0.001], absence of rapid cycling (OR for rapid cycling: 0.30; 95% CI: 0.17, 0.53; P < 0.001), absence of psychotic symptoms (OR for psychotic symptoms: 0.52; 95% CI: 0.34, 0.79; P = 0.002), family history of bipolar disorder (OR: 1.61; 95% CI: 1.03, 2.52; P = 0.036), shorter prelithium illness duration [standardised mean difference (SMD): -0.26; 95% CI: -0.41, -0.12; P < 0.001] and later age of onset (SMD: 0.17; 95% CI: 0.02, 0.36; P = 0.029). Additionally, higher body mass index was associated with poor response in two studies (SMD: -0.61; 95% CI: -0.90, -0.32; P < 0.001). There was weak evidence for number of episodes prior to lithium treatment (SMD: -0.42; 95% CI: -0.84, -0.01; P = 0.046), number of hospitalisations before lithium (SMD: -0.40; 95% CI: -0.81, 0.01; P = 0.055) and family history of lithium response (OR: 10.28; 95% CI: 0.66, 161.26; P = 0.097). CONCLUSIONS: The relative importance of these clinical characteristics should be interpreted with caution because of potential biases and confounding.

What are the effects of preventative interventions on major depressive disorder (MDD) in young adults? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a prevalent disorder with a peak rate of onset in young adulthood from 18 to 25 years. To date, no review has systematically assessed the effectiveness of programs that aim to reduce depressive symptoms or diagnosis of depression in young adults. METHOD: A systematic search was performed in Cochrane, PubMed, PsycINFO and EMBASE. We performed a random-effects meta-analysis of the randomized controlled studies that compared an intervention for young adults (aged 18-25) without a diagnosis or history of depression and a control condition. Comparisons between intervention and control group outcomes were carried out at the post-intervention time point. We also compared intervention and control group outcomes at later follow-up time points where data were available. RESULTS: Twenty-six randomized controlled trials among 2865 young adults were included in the analysis. The pooled effect size of the interventions versus control at post-intervention was g = 0.37 (95% CI: 0.28-0.47, NNT = 9) and heterogeneity was moderate I2 = 36 (95% CI: 11-64). There were no significant effects in terms of the type of delivery, focus of study, type of control, or type of support within the interventions. LIMITATIONS: The authors were unable to assess the effects of interventions on the onset of depression as none of the included studies measured incidence. The risk of bias was high in most studies (81%). Only one study included a follow-up of more than a year. Demographic factors were inconsistently reported in the included articles. CONCLUSION: While it was not possible to investigate the effects of interventions on depression incidence, some evidence was found for the effectiveness of preventative interventions in reducing depressive symptoms in young adults. Future research should address limitations of the current evidence base to allow stronger conclusions to be drawn.

Effects of aging on T1, T2*, and QSM MRI values in the subcortex.

The aging brain undergoes several anatomical changes that can be measured with Magnetic Resonance Imaging (MRI). Early studies using lower field strengths have assessed changes in tissue properties mainly qualitatively, using [Formula: see text]- or [Formula: see text]- weighted images to provide image contrast. With the development of higher field strengths (7 T and above) and more advanced MRI contrasts, quantitative measures can be acquired even of small subcortical structures. This study investigates volumetric, spatial, and quantitative MRI parameter changes associated with healthy aging in a range of subcortical nuclei, including the basal ganglia, red nucleus, and the periaqueductal grey. The results show that aging has a heterogenous effects across regions. Across the subcortical areas an increase of [Formula: see text] values is observed, most likely indicating a loss of myelin. Only for a number of areas, a decrease of [Formula: see text] and increase of QSM is found, indicating an increase of iron. Aging also results in a location shift for a number of structures indicating the need for visualization of the anatomy of individual brains.

Discovery of biologically active peptides in random libraries: solution-phase testing after staged orthogonal release from resin beads.

To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.