BackgroundUnderstanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder. Nevertheless, some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.AimsTo examine the prevalence rates of sleep and circadian dysfunctions, mental disorders and their symptoms in the offspring of parents with (O-BD) and without bipolar disorder (O-control).MethodsThe study included 191 O-BD and 202 O-control subjects aged 6–21 years from the Greater Bay Area, China. The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders, and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, respectively. Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.ResultsAdjusting for age, sex and region of recruitment, there was a significantly higher risk of delayed sleep phase symptoms (9.55% vs 2.58%, adjusted OR: 4.04) in O-BD than in O-control. O-BD had a nearly fivefold higher risk of mood disorders (11.70% vs 3.47%, adjusted OR: 4.68) and social anxiety (6.28% vs 1.49%, adjusted OR: 4.70), a fourfold higher risk of depressive disorders (11.17% vs 3.47%, adjusted OR: 3.99) and a threefold higher risk of mood symptoms (20.74% vs 10.40%, adjusted OR: 2.59) than O-control. Subgroup analysis revealed that O-BD children (aged under 12 years) had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control, while there was a nearly 4-fold higher risk of delayed sleep phase symptoms, a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents (aged 12 years and over).ConclusionsThere was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts, confirming the central role of circadian rhythm dysfunction in bipolar disorder. The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.Trial registration numberNCT03656302.

BackgroundThere is limited evidence suggesting that osteoporosis might exacerbate depressive symptoms, while more studies demonstrate that depression negatively affects bone density and increases fracture risk.AimsTo explore the relationship between major depressive disorder (MDD) and fracture risk.MethodsWe conducted a nested case-control analysis (32 670 patients with fracture and 397 017 individuals without fracture) and a matched cohort analysis (16 496 patients with MDD and 435 492 individuals without MDD) in the same prospective UK Biobank data set. Further, we investigated the shared genetic architecture between MDD and fracture with linkage disequilibrium score regression and the MiXeR statistical tools. We used the conditional/conjunctional false discovery rate approach to identify the specific shared loci. We calculated the weighted genetic risk score for individuals in the UK Biobank and logistic regression was used to confirm the association observed in the prospective study.ResultsWe found that MDD was associated with a 14% increase in fracture risk (hazard ratio (HR) 1.14, 95% CI 1.14 to 1.15, p<0.001) in the nested case-control analysis, while fracture was associated with a 72% increase in MDD risk (HR 1.72, 95% CI 1.64 to 1.79, p<0.001) in the matched cohort analysis, suggesting a longitudinal and bidirectional relationship. Further, genetic summary data suggested a genetic overlap between MDD and fracture. Specifically, we identified four shared genomic loci, with the top signal (rs7554101) near SGIP1. The protein encoded by SGIP1 is involved in cannabinoid receptor type 1 signalling. We found that genetically predicted MDD was associated with a higher risk of fracture and vice versa. In addition, we found that the higher expression level of SGIP1 in the spinal cord and muscle was associated with an increased risk of fracture and MDD.ConclusionsThe genetic pleiotropy between MDD and fracture highlights the bidirectional association observed in the epidemiological analysis. The shared genetic components (such as SGIP1) between the diseases suggest that modulating the endocannabinoid system could be a potential therapeutic strategy for both MDD and bone loss.

BackgroundGrowing evidence attests to the efficacy of mindfulness-based interventions (MBIs), but their effectiveness for healthcare workers remains uncertain.AimsTo evaluate the evidence for MBIs in improving healthcare workers’ psychological well-being.MethodsA systematic literature search was conducted on Medline, Embase, Cumulative Index for Nursing and Allied Health Literature, PsycINFO and Cochrane Central Register of Controlled Trials up to 31 August 2022 using the keywords ‘healthcare worker’, ‘doctor’, ‘nurse’, ‘allied health’, ‘mindfulness’, ‘wellness’, ‘workshop’ and ‘program’. Randomised controlled trials with a defined MBI focusing on healthcare workers and quantitative outcome measures related to subjective or psychological well-being were eligible for inclusion. R V.4.0.3 was used for data analysis, with the standardised mean difference as the primary outcome, employing DerSimonian and Laird’s random effects model. Grading of Recommendations, Assessment, Development and Evaluation framework was used to evaluate the quality of evidence. Cochrane’s Risk of Bias 2 tool was used to assess the risk of bias in the included studies.ResultsA total of 27 studies with 2506 participants were included, mostly from the USA, involving various healthcare professions. MBIs such as stress reduction programmes, apps, meditation and training showed small to large effects on anxiety, burnout, stress, depression, psychological distress and job strain outcomes of the participants. Positive effects were also seen in self-compassion, empathy, mindfulness and well-being. However, long-term outcomes (1 month or longer postintervention) varied, and the effects were not consistently sustained.ConclusionsMBIs offer short-term benefits in reducing stress-related symptoms in healthcare workers. The review also highlights limitations such as intervention heterogeneity, reduced power in specific subgroup analyses and variable study quality.PROSPERO registration numberCRD42022353340.

BackgroundThe role of human lineage mutations (HLMs) in human evolution through post-transcriptional modification is unclear.AimsTo investigate the contribution of HLMs to human evolution through post-transcriptional modification.MethodsWe applied a deep learning model Seqweaver to predict how HLMs impact RNA-binding protein affinity.ResultsWe found that only 0.27% of HLMs had significant impacts on RNA-binding proteins at the threshold of the top 1% of human common variations. These HLMs enriched in a set of conserved genes highly expressed in adult excitatory neurons and prenatal Purkinje neurons, and were involved in synapse organisation and the GTPase pathway. These genes also carried excess damaging coding mutations that caused neurodevelopmental disorders, ataxia and schizophrenia. Among these genes, NTRK2 and ITPR1 had the most aggregated evidence of functional importance, suggesting their essential roles in cognition and bipedalism.ConclusionsOur findings suggest that a small subset of human-specific mutations have contributed to human speciation through impacts on post-transcriptional modification of critical brain-related genes.

BackgroundDepressive symptoms are established risk factors for various health outcomes. However, previous studies assessed depressive symptoms at a single time point, neglecting individual variations over time.AimsTo identify depressive symptoms trajectories through repeated measures and examine their associations with cardiovascular disease (CVD), cancer and mortality.MethodsThis study included 20 634 UK Biobank participants free of CVD and cancer at baseline with two or more assessments of depressive symptoms during 2006–2016. Group-based trajectory modelling identified depressive symptoms trajectories. Incident CVD, cancer and mortality were followed up until 2021 through linked registries.ResultsSix depressive symptoms trajectories were identified: no symptoms (n=6407), mild-stable (n=11 539), moderate-stable (n=2183), severe-decreasing (n=206), moderate-increasing (n=177) and severe-stable (n=122). During a median follow-up of 5.5 years, 1471 CVD cases, 1275 cancer cases and 503 deaths were documented. Compared with the no symptoms trajectory, the mild-stable, moderate-stable and severe-stable trajectories exhibited higher CVD risk, with hazard ratios (HRs) (95% CIs) of 1.19 (1.06 to 1.34), 1.32 (1.08 to 1.34) and 2.99 (1.85 to 4.84), respectively. Moderate-increasing and severe-stable trajectories were associated with higher mortality risks, with HRs (95% CIs) of 2.27 (1.04 to 4.93) and 3.26 (1.55 to 6.88), respectively. However, the severe-decreasing trajectory was not associated with higher risks of adverse outcomes. We did not find significant associations between any trajectory and cancer.ConclusionsTrajectories related to stable and increasing depressive symptoms, but not the trajectory associated with severe depressive symptoms at the initial assessment but decreasing at the follow-up, were associated with higher risks of CVD and mortality. Alleviating severe depressive symptoms at the initial onset may mitigate CVD and mortality risks.

BackgroundAnorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN.AimsThe study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN.MethodsIn this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline.ResultsAmong the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN.ConclusionsAlterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.