Blood perfusion changes during sacral nerve root stimulation versus surface gluteus electrical stimulation on in seated spinal cord injury

Objective: To examine dynamic changes of ischial blood perfusion during sacral nerve root stimulation against surface functional electrical stimulation (FES). Methods: Fourteen adults with suprasacral complete spinal cord injury were recruited. The gluteal maximus was activated by surface FES or stimulating sacral nerve roots by functional magnetic stimulation (FMS) or a sacral anterior root stimulator implant (SARS). Ischial skin index of haemoglobin (IHB) and oxygenation (IOX) was measured. Results: Skin blood perfusion was significantly higher during FMS than the baseline (IHB 1.05±0.21 before vs. 1.08±0.02 during stimulation, P=0.03; IOX 0.18 ± 0.21 before vs. 0.46 ± 0.30, P=0.01 during stimulation, n=6). Similarly, when using the SARS implant, we also observed that blood perfusion significantly increased (IHB 1.01 ± 0.02 before vs. 1.07 ±0.02 during stimulation, P=0.003; IOX 0.79±0.81 before vs. 2.2±1.21 during stimulation, P=0.03, n=6). However, there was no significant change of blood perfusion during surface FES. Among 4 participants who completed both the FMS and FES studies, the magnitude of increase in both parameters was significantly higher during FMS. Conclusion: This study demonstrates that using SARS implant is more efficient to activate gluteal muscles and confer better benefit on blood perfusion than applying traditional FES in SCI population

Association of central adiposity with psoriasis, psoriatic arthritis and rheumatoid arthritis: a cross-sectional study of the UK Biobank

Objectives: To determine the independent association of central adiposity, assessed by waist circumference, with odds of psoriasis, PsA and RA prevalence after controlling for general adiposity (BMI). Methods: A cross-sectional study of UK Biobank participants aged 40–70 years was performed. Logistic regression was used to calculate the odds of psoriasis, PsA and RA occurrence compared with controls without these conditions by waist circumference, adjusting for covariates: age, sex, smoking status, socioeconomic deprivation and self-reported physical activity (Model 1), followed additionally by BMI (Model 2). Results: A total of 502 417 participants were included; 5074 with psoriasis (1.02%), 905 with PsA (0.18%), 5532 with RA (1.11%) and 490 906 controls without these conditions. Adjusted odds ratios (ORs) (Model 1) for psoriasis, PsA and RA, per S.D. (13.5 cm) higher waist circumference were 1.20 (95% CI 1.16, 1.23), 1.30 (95% CI 1.21, 1.39) and 1.21 (95% CI 1.17, 1.24), respectively (all P < 0.001). These ORs remained significant after further adjustment for BMI (Model 2) in psoriasis [OR 1.19 (95% CI 1.12, 1.27), P < 0.001] and RA [OR 1.19 (95% CI 1.12, 1.26), P < 0.001], but not in PsA [OR 1.11 (95% CI 0.95, 1.29), P = 0.127]. Conclusion: Central adiposity as measured by waist circumference is associated with greater odds of psoriasis and RA prevalence after adjustment for confounders and for BMI. Our findings add support for central adiposity as a long-term clinically relevant component of these conditions

Association of injury related hospital admissions with commuting by bicycle in the UK: prospective population based study

Objective: To determine whether bicycle commuting is associated with risk of injury. Design: Prospective population based study. Setting: UK Biobank. Participants: 230 390 commuters (52.1% women; mean age 52.4 years) recruited from 22 sites across the UK compared by mode of transport used (walking, cycling, mixed mode versus non-active (car or public transport)) to commute to and from work on a typical day. Main outcome measure: First incident admission to hospital for injury. Results: 5704 (2.5%) participants reported cycling as their main form of commuter transport. Median follow-up was 8.9 years (interquartile range 8.2-9.5 years), and overall 10 241 (4.4%) participants experienced an injury. Injuries occurred in 397 (7.0%) of the commuters who cycled and 7698 (4.3%) of the commuters who used a non-active mode of transport. After adjustment for major confounding sociodemographic, health, and lifestyle factors, cycling to work was associated with a higher risk of injury compared with commuting by a non-active mode (hazard ratio 1.45, 95% confidence interval 1.30 to 1.61). Similar trends were observed for commuters who used mixed mode cycling. Walking to work was not associated with a higher risk of injury. Longer cycling distances during commuting were associated with a higher risk of injury, but commute distance was not associated with injury in non-active commuters. Cycle commuting was also associated with a higher number of injuries when the external cause was a transport related incident (incident rate ratio 3.42, 95% confidence interval 3.00 to 3.90). Commuters who cycled to work had a lower risk of cardiovascular disease, cancer, and death than those who did not. If the associations are causal, an estimated 1000 participants changing their mode of commuting to include cycling for 10 years would result in 26 additional admissions to hospital for a first injury (of which three would require a hospital stay of a week or longer), 15 fewer first cancer diagnoses, four fewer cardiovascular disease events, and three fewer deaths. Conclusion: Compared with non-active commuting to work, commuting by cycling was associated with a higher risk of hospital admission for a first injury and higher risk of transport related incidents specifically. These risks should be viewed in context of the health benefits of active commuting and underscore the need for a safer infrastructure for cycling in the UK

Carotid intima-media thickness novel loci, sex-specific effects, and genetic correlations with obesity and glucometabolic traits in UK Biobank

Objective: Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements. Approach and Results: We used BOLT-LMM to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight VCAN as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease. Conclusions: These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression

Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with MDD, anxiety disorder and schizophrenia

Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD (r g = 0.60, SE = 0.07, p = 8.95 × 10−17) and a small but significant genetic correlation with both schizophrenia (r g = 0.11, SE = 0.04, p = 0.01) and anxiety disorders (r g = 0.28, SE = 0.14, p = 0.04), although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation

Seasonality of depressive symptoms in women but not in men: a cross-sectional study in the UK Biobank cohort

Background: We examined whether seasonal variations in depressive symptoms occurred independently of demographic and lifestyle factors, and were related to change in day length and/or outdoor temperature. Methods: In a cross-sectional analysis of >150,000 participants of the UK Biobank cohort, we used the cosinor method to assess evidence of seasonality of a total depressive symptoms score and of low mood, anhedonia, tenseness and tiredness scores in women and men. Associations of depressive symptoms with day length and mean outdoor temperature were then examined. Results: Seasonality of total depressive symptom scores, anhedonia and tiredness scores was observed in women but not men, with peaks in winter. In women, increased day length was associated with reduced low mood and anhedonia scores, independent of demographic and lifestyle factors. For women, longer day length was associated with increased tiredness. Associations with day length were not independent of the average outdoor temperature preceding assessment. Limitations: This was a cross-sectional investigation – longitudinal studies of within-subject seasonal variation in mood are necessary. Outcome measures relied on self-report and measured only a subset of depressive symptoms. Conclusion: This large, population-based study provides evidence of seasonal variation in depressive symptoms in women. Shorter days were associated with increased feelings of low mood and anhedonia in women. Clinicians should be aware of these population-level sex differences in seasonal mood variations in order to aid recognition and treatment of depression and subclinical depressive symptoms

Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91 105 participants from the UK Biobank

Background: Disruption of sleep and circadian rhythmicity is a core feature of mood disorders and might be associated with increased susceptibility to such disorders. Previous studies in this area have used subjective reports of activity and sleep patterns, but the availability of accelerometer-based data from UK Biobank participants permits the derivation and analysis of new, objectively ascertained circadian rhythmicity parameters. We examined associations between objectively assessed circadian rhythmicity and mental health and wellbeing phenotypes, including lifetime history of mood disorder. Methods: UK residents aged 37–73 years were recruited into the UK Biobank general population cohort from 2006 to 2010. We used data from a subset of participants whose activity levels were recorded by wearing a wrist-worn accelerometer for 7 days. From these data, we derived a circadian relative amplitude variable, which is a measure of the extent to which circadian rhythmicity of rest–activity cycles is disrupted. In the same sample, we examined cross-sectional associations between low relative amplitude and mood disorder, wellbeing, and cognitive variables using a series of regression models. Our final model adjusted for age and season at the time that accelerometry started, sex, ethnic origin, Townsend deprivation score, smoking status, alcohol intake, educational attainment, overall mean acceleration recorded by accelerometry, body-mass index, and a binary measure of childhood trauma. Findings: We included 91 105 participants with accelerometery data collected between 2013 and 2015 in our analyses. A one-quintile reduction in relative amplitude was associated with increased risk of lifetime major depressive disorder (odds ratio [OR] 1·06, 95% CI 1·04–1·08) and lifetime bipolar disorder (1·11, 1·03–1·20), as well as with greater mood instability (1·02, 1·01–1·04), higher neuroticism scores (incident rate ratio 1·01, 1·01–1·02), more subjective loneliness (OR 1·09, 1·07–1·11), lower happiness (0·91, 0·90–0·93), lower health satisfaction (0·90, 0·89–0·91), and slower reaction times (linear regression coefficient 1·75, 1·05–2·45). These associations were independent of demographic, lifestyle, education, and overall activity confounders. Interpretation: Circadian disruption is reliably associated with various adverse mental health and wellbeing outcomes, including major depressive disorder and bipolar disorder. Lower relative amplitude might be linked to increased susceptibility to mood disorders

Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide

Background: Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic. Methods: Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: ‘no suicidality’ controls (N = 83,557); ‘thoughts that life was not worth living’ (N = 21,063); ‘ever contemplated self-harm’ (N = 13,038); ‘act of deliberate self-harm in the past’ (N = 2498); and ‘previous suicide attempt’ (N = 2666). Outcomes: We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81). Interpretation: These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level

The genomic basis of mood instability:identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function

Genome-wide association studies (GWAS) of psychiatric phenotypes have tended to focus on categorical diagnoses, but to understand the biology of mental illness it may be more useful to study traits which cut across traditional boundaries. Here, we report the results of a GWAS of mood instability as a trait in a large population cohort (UK Biobank, n = 363,705). We also assess the clinical and biological relevance of the findings, including whether genetic associations show enrichment for nervous system pathways. Forty six unique loci associated with mood instability were identified with a SNP heritability estimate of 9%. Linkage Disequilibrium Score Regression (LDSR) analyses identified genetic correlations with Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia, anxiety, and Post Traumatic Stress Disorder (PTSD). Gene-level and gene set analyses identified 244 significant genes and 6 enriched gene sets. Tissue expression analysis of the SNP-level data found enrichment in multiple brain regions, and eQTL analyses highlighted an inversion on chromosome 17 plus two brain-specific eQTLs. In addition, we used a Phenotype Linkage Network (PLN) analysis and community analysis to assess for enrichment of nervous system gene sets using mouse orthologue databases. The PLN analysis found enrichment in nervous system PLNs for a community containing serotonin and melatonin receptors. In summary, this work has identified novel loci, tissues and gene sets contributing to mood instability. These findings may be relevant for the identification of novel trans-diagnostic drug targets and could help to inform future stratified medicine innovations in mental health