Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life.

Data from the UK Biobank were available for 966 participants with BD, aged between 40 and 69 years. Individual cardiometabolic disease risk factors were initially regressed onto a global cognition score in separate models for the following risk factor domains; (1) health risk behaviors (physical activity, sedentary behavior, smoking, and sleep) and (2) physiological risk factors, stratified into (2a) anthropometric and clinical risk (handgrip strength, body composition, and blood pressure), and (2b) cardiometabolic disease risk biomarkers (CRP, lipid profile, and HbA1c). A final combined multivariate regression model for global cognition was then fitted, including only the predictor variables that were significantly associated with cognition in the previous models.

In the final combined model, lower mentally active and higher passive sedentary behavior, higher levels of physical activity, inadequate sleep duration, higher systolic and lower diastolic blood pressure, and lower handgrip strength were associated with worse global cognition.

Health risk behaviors, as well as blood pressure and muscular strength, are associated with cognitive function in BD, whereas other traditional physiological cardiometabolic disease risk factors are not.

Wellbeing is relatively stable over the life span. However, individuals differ in this stability and change. One explanation for these differences could be the influence of different genetic or environmental factors on wellbeing over time.

To investigate causes of stability and change of wellbeing across the lifespan, we used cohort-sequential data on wellbeing from twins and their siblings of the Netherlands Twin Register (NTR) (total N = 46.885, 56% females). We organized wellbeing data in multiple age groups, from childhood (age 5), to adolescence, up to old age (age 61+). Applying a longitudinal genetic simplex model, we investigated the phenotypic stability of wellbeing and continuity and change in genetic and environmental influences.

Wellbeing peaked in childhood, decreased during adolescence, and stabilized during adulthood. In childhood and adolescence, around 40% of the individual differences was explained by genetic effects. The heritability decreased toward old adulthood (35–24%) and the contribution of unique environmental effects increased to 76%. Environmental innovation was found at every age, whereas genetic innovation was only observed during adolescence (10–18 years). In childhood and adulthood, the absence of genetic innovation indicates a stable underlying set of genes influencing wellbeing during these life phases.

These findings provide insights into the stability and change of wellbeing and the genetic and environmental influences across the lifespan. Genetic effects were mostly stable, except in adolescence, whereas the environmental innovation at every age suggests that changing environmental factors are a source of changes in individual differences in wellbeing over time.

Class and social disadvantage have long been identified as significant factors in the etiology and epidemiology of psychosis. Few studies have explicitly examined the impact of intersecting social disadvantage on long-term employment and financial independence.

We applied latent class analysis (LCA) to 20-year longitudinal data from participants with affective and non-affective psychosis (n = 256) within the Chicago Longitudinal Research. LCA groups were modeled using multiple indicators of pre-morbid disadvantage (parental social class, educational attainment, race, gender, and work and social functioning prior to psychosis onset). The comparative longitudinal work and financial functioning of LCA groups were then examined.

We identified three distinct latent classes: one comprised entirely of White participants, with the highest parental class and highest levels of educational attainment; a second predominantly working-class group, with equal numbers of Black and White participants; and a third with the lowest parental social class, lowest levels of education and a mix of Black and White participants. The latter, our highest social disadvantage group experienced significantly poorer employment and financial outcomes at all time-points, controlling for diagnosis, symptoms, and hospitalizations prior to baseline. Contrary to our hypotheses, on most measures, the two less disadvantaged groups did not significantly differ from each other.

Our analyses add to a growing literature on the impact of multiple forms of social disadvantage on long-term functional trajectories, underscoring the importance of proactive attention to sociostructural disadvantage early in treatment, and the development and evaluation of interventions designed to mitigate ongoing social stratification.

In males, the relationship between pubertal timing and depression is understudied and less consistent than in females, likely for reasons of unmeasured confounding. To clarify this relationship, a combined epidemiological and genetic approach was chosen to exploit the methodological advantages of both approaches.

Data from 2026 males from a nationwide, representative study were used to investigate the non-/linear relationship between pubertal timing defined by the age at voice break and depression, considering a multitude of potential confounders and their interactions with pubertal timing. This analysis was complemented by Mendelian randomization (MR), which is robust to inferential problems inherent to epidemiological studies. We used 71 single nucleotide polymorphisms related to pubertal timing in males as instrumental variable to clarify its causal relationship with depression based on data from 807 553 individuals (246 363 cases and 561 190 controls) by univariable and multivariable MR, including BMI as pleiotropic phenotype.

Univariable MR indicated a causal effect of pubertal timing on depression risk (inverse-variance weighted: OR 0.93, 95%-CI [0.87–0.99)], p = 0.03). However, this was not confirmed by multivariable MR (inverse-variance weighted: OR 0.95, 95%-CI [0.88–1.02)], p = 0.13), consistent with the epidemiological approach (OR 1.01, 95%-CI [0.81–1.26], p = 0.93). Instead, the multivariable MR study indicated a causal relationship of BMI with depression by two of three methods.

Pubertal timing is not related to MDD risk in males.

Research on the Alternative DSM-5 Model for Personality Disorders (AMPD) in DSM-5's Section-III has demonstrated acceptable interrater reliability, a largely consistent latent structure, substantial correlations with theoretically and clinically relevant measures, and evidence for incremental concurrent and predictive validity after controlling for DSM-5's Section II categorical personality disorders (PDs). However, the AMPD is not yet widely used clinically. One clinician concern may be caseness – that the new model will diagnose a different set of PD patients from that with which they are familiar. The primary aim of this study is to determine whether this concern is valid, by testing how well the two models converge in terms of prevalence and coverage.

Participants were 305 psychiatric outpatients and 302 community residents not currently in mental-health treatment who scored above threshold on the Iowa Personality Disorder Screen (Langbehn et al., 1999). Participants were administered a semi-structured interview for DSM-5 PD, which was scored for both Section II and III PDs.

Convergence across the two PD models was variable for specific PDs, Good when specific PDs were aggregated, and Very Good for ‘any PD.’

Results provide strong evidence that the AMPD yields the same overall prevalence of PD as the current model and, further, identifies largely the same overall population. It also addresses well-known problems of the current model, is more consistent with the ICD-11 PD model, and provides more complete, individualized characterizations of persons with PD, thereby offering multiple reasons for its implementation in clinical settings.

Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs).

We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons.

Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction).

Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

A large and accumulating body of evidence shows that loneliness is detrimental for various health and well-being outcomes. However, less is known about potentially modifiable factors that lead to decreased loneliness.

We used data from the Health and Retirement Study to prospectively evaluate a wide array of candidate predictors of subsequent loneliness. Importantly, we examined if changes in 69 physical-, behavioral-, and psychosocial-health factors (from t0;2006/2008 to t1;2010/2012) were associated with subsequent loneliness 4 years later (t2;2014/2016).

Adjusting for a large range of covariates, changes in certain health behaviors (e.g. increased physical activity), physical health factors (e.g. fewer functioning limitations), psychological factors (e.g. increased purpose in life, decreased depression), and social factors (e.g. greater number of close friends) were associated with less subsequent loneliness.

Our findings suggest that subjective ratings of physical and psychological health and perceived social environment (e.g. chronic pain, self-rated health, purpose in life, anxiety, neighborhood cohesion) are more strongly associated with subsequent loneliness. Yet, objective ratings (e.g. specific chronic health conditions, living status) show less evidence of associations with subsequent loneliness. The current study identified potentially modifiable predictors of subsequent loneliness that may be important targets for interventions aimed at reducing loneliness.

The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.

We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.

In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.

Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.

Mild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown.

Children with a history of mTBI (n = 406; Mage = 10 years, SDage = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or 8-10 years to the respective matched TDC controls. Fractional anisotropy (FA) and mean diffusivity (MD), both MRI-based measures of white matter microstructure, were compared between children with mTBI and controls.

Children with a history of mTBI displayed higher parent-rated executive dysfunction, higher impulsivity, and poorer self-regulation compared to both control groups. At closer investigation, these differences to TDC were only present in one respective age-at-injury group. No alterations were found in task-based executive functioning or white matter microstructure.

Findings suggest that everyday executive function, impulsivity, and emotion-regulation are affected years after pediatric mTBI. Outcomes were specific to the age at which the injury occurred, suggesting that functioning is differently affected by pediatric mTBI during vulnerable periods. Groups did not differ in white matter microstructure.

Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear.

The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength – specifically between the anterior caudate and dlPFC – differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality.

Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality.

Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Emotional problems, especially anxiety, have become increasingly common in recent generations. Few population-based studies have examined trajectories of emotional problems from early childhood to late adolescence or investigated differences in psychiatric and functional outcomes.

Using the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 8286, 50.4% male), we modeled latent class growth trajectories of emotional problems, using the parent-reported Strength and Difficulties Questionnaire emotional scale (SDQ-E) on seven occasions (4–17 years). Psychiatric outcomes in young adulthood (21–25 years) were major depressive disorder (MDD), generalized anxiety disorder (GAD), and self-harm. Functional outcomes were exam attainment, educational/occupational status, and social relationship quality.

We identified four classes of emotional problems: low (67.0%), decreasing (18.4%), increasing (8.9%), and persistent (5.7%) problems. Compared to those in the low class, individuals with decreasing emotional problems were not at elevated risk of any poor adult outcome. Individuals in the increasing and persistent classes had a greater risk of adult MDD (RR: 1.59 95% CI 1.13–2.26 and RR: 2.25 95% CI 1.49–3.41) and self-harm (RR: 2.37 95% CI 1.91–2.94 and RR: 1.87 95% CI 1.41–2.48), and of impairment in functional domains. Childhood sleep difficulties, irritability, conduct and neurodevelopmental problems, and family adversity were associated with a persistent course of emotional problems.

Childhood emotional problems were common, but those whose symptoms improved over time were not at increased risk for adverse adult outcomes. In contrast, individuals with persistent or adolescent-increasing emotional problems had a higher risk of mental ill-health and social impairment in young adulthood which was especially pronounced for those with persistent emotional problems.

Post-traumatic stress symptoms (PTSS) were the most frequently reported mental health concern for youth during COVID-19, yet variations in youth's PTSS responses warrant empirical consideration. Features of the caregiving environment influence youth's responses to environmental stressors, and youth's parasympathetic nervous system regulation may qualify the magnitude and/or direction of these effects. This prospective investigation evaluated diathesis stress and differential susceptibility models of caregiving and parasympathetic influences on youth's PTSS responses to COVID-19.

Participants were 225 caregiver-youth dyads (youth 49.8% female at birth; 88.4% non-white) followed from childhood through adolescence and COVID-19. Youth's resting respiratory sinus arrhythmia (RSA; Mage = 6.11, s.d. = 0.21), caregiving features (i.e. attachment security [youth Mage = 12.24, s.d. = 0.35] and caregiver internalizing psychopathology [caregiver Mage = 39.29, s.d. = 6.78]) were assessed pre-pandemic. Youth's PTSS was assessed one year prior to the US COVID-19 pandemic (Mage = 14.24, s.d. = 0.50) and during the spring of 2020 at the height of the pandemic (Mage = 15.23, s.d. = 0.57).

Youth's PTSS increased during COVID-19. Youth with relatively high resting RSA evidenced the lowest PTSS when their caregiving environment featured high attachment security or low caregiver internalizing problems, but the highest PTSS when their caregiving environment featured low attachment security or high caregiver internalizing problems. In contrast, PTSS levels of youth with relatively low or average resting RSA did not differ significantly depending on attachment security or caregiver internalizing.

Results are consistent with a differential susceptibility hypothesis, wherein relatively high resting RSA conferred heightened sensitivity to caregiving environments in a for-better-and-for-worse manner during COVID-19.

Comorbid depression substantially affects the management of glycemia and diabetes-related complications among patients with type 2 diabetes mellitus. In this study, we sought to determine the association between weight change over 4 years and depression risk among patients with type 2 diabetes mellitus.

This population-based retrospective cohort study from the National Health Insurance Services of Korea included 1 111 345 patients with type 2 diabetes who were divided into groups according to body weight change over 4 years. Body weight changes were compared with the preceding 4-year period (2005–2008). Depression was defined according to the International Classification of Diseases 10th revision code for depression (F32 and F33) on one or more inpatient or outpatient claims.

During a median follow-up of 7.4 years, 244 081 cases of depression were identified. We observed a U-shaped association between body weight change and depression risk with a higher risk among both groups of weight loss (hazard ratio (HR) 1.17, 95% CI 1.15–1.19 for ⩾ −10%; HR 1.07, 95% CI 1.06–1.08 for −10 to −5%) and weight gain (HR 1.06, 95% CI 1.04–1.08 for ⩾10%; HR 1.02, 95% CI 1.01–1.04 for 5–10%) compared with the stable weight group (−5 to 5%).

A U-shaped association between body weight change and depression risk was observed in this large nationwide cohort study. Our study suggests that patients with type 2 diabetes and weight change, either gain or loss, could be considered a high-risk group for depression.

Major depressive disorder (MDD) is highly prevalent and burdensome for individuals and society. While there are psychological interventions able to prevent and treat MDD, uptake remains low. To overcome structural and attitudinal barriers, an indirect approach of using online insomnia interventions seems promising because insomnia is less stigmatized, predicts MDD onset, is often comorbid and can outlast MDD treatment. This individual-participant-data meta-analysis evaluated the potential of the online insomnia intervention GET.ON Recovery as an indirect treatment to reduce depressive symptom severity (DSS) and potential MDD onset across a range of participant characteristics.

Efficacy on depressive symptom outcomes was evaluated using multilevel regression models controlling for baseline severity. To identify potential effect moderators, clinical, sociodemographic, and work-related variables were investigated using univariable moderation and random-forest methodology before developing a multivariable decision tree.

IPD were obtained from four of seven eligible studies (N = 561); concentrating on workers with high work-stress. DSS was significantly lower in the intervention group both at post-assessment (d = −0.71 [95% CI−0.92 to −0.51]) and at follow-up (d = −0.84 [95% CI −1.11 to −0.57]). In the subsample (n = 121) without potential MDD at baseline, there were no significant group differences in onset of potential MDD. Moderation analyses revealed that effects on DSS differed significantly across baseline severity groups with effect sizes between d = −0.48 and −0.87 (post) and d = − 0.66 to −0.99 (follow-up), while no other sociodemographic, clinical, or work-related characteristics were significant moderators.

An online insomnia intervention is a promising approach to effectively reduce DSS in a preventive and treatment setting.

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.

Longitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010–2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence (low, n = 5225 [87.8%]); early increasing, then chronic high prevalence (early-chronic, n = 157 [2.6%]); low, then increasing prevalence (late-increasing, n = 247 [4.2%]); and remitting prevalence (remitting, n = 323 [5.4%]).

After a median follow-up of 7.0 years (range 1.0–11.0), 806 (13.5%) individuals had incident clinically relevant depressive symptoms. After full adjustment, a larger CRAE and CRVE were each associated with a lower risk of clinically relevant depressive symptoms (hazard ratios [HRs] per standard deviation [s.d.]: 0.89 [95% confidence interval (CI) 0.83–0.96] and 0.93 [0.86–0.99], respectively), while a lower flicker light-induced retinal dilation was associated with a higher risk of clinically relevant depressive symptoms (HR per s.d.: 1.10 [1.01–1.20]). Compared to the low trajectory, a larger CRAE was associated with lower odds of belonging to the early-chronic trajectory (OR: 0.83 [0.69–0.99]) and a lower flicker light-induced retinal dilation was associated with higher odds of belonging to the remitting trajectory (OR: 1.23 [1.07–1.43]).

These findings support the hypothesis that cerebral microvascular dysfunction contributes to the development of depressive symptoms.

Cardiac vagal tone is an indicator of parasympathetic nervous system functioning, and there is increasing interest in its relation to antisocial behavior. It is unclear however whether antisocial individuals are characterized by increased or decreased vagal tone, and whether increased vagal tone is the source of the low heart rate frequently reported in antisocial populations.

Participants consisted of four groups of community-dwelling adolescent boys aged 15.7 years: (1) controls, (2) childhood-only antisocial, (3) adolescent-only antisocial, and (4) persistently antisocial. Heart rate and vagal tone were assessed in three different conditions: rest, cognitive stressor, and social stressor.

All three antisocial groups had both lower resting heart rates and increased vagal tone compared to the low antisocial controls across all three conditions. Low heart rate partially mediated the relationship between vagal tone and antisocial behavior.

Results indicate that increased vagal tone and reduced heart rate are relatively broad risk factors for different developmental forms of antisocial behavior. Findings are the first to implicate vagal tone as an explanatory factor in understanding heart rate – antisocial behavior relationships. Future experimental work using non-invasive vagus nerve stimulation or heart rate variability biofeedback is needed to more systematically evaluate this conclusion.

Although suicide bereavement is associated with suicide and self-harm, evidence regarding mechanisms is lacking. We investigated whether depression and substance use (alcohol and/or other drugs) explain the association between partner suicide bereavement and suicide.

Linkage of nationwide, longitudinal data from Denmark for the period 1980–2016 facilitated a comparison of 22 668 individuals exposed to bereavement by a partner's suicide with 913 402 individuals bereaved by a partner's death due to other causes. Using causal mediation models, we estimated the degree to which depression and substance use (considered separately) mediated the association between suicide bereavement and suicide.

Suicide-bereaved partners were found to have a higher risk of suicide (HRadj = 1.59, 95% CI 1.36–1.86) and of depression (ORadj 1.16, 95% CI 1.09–1.25) when compared to other-bereaved partners, but a lower risk of substance use (ORadj 0.83; 95% CI 0.78–0.88). An increased risk of suicide was found among any bereaved individuals with a depression diagnosis recorded post-bereavement (ORadj 3.92, 95% CI 3.55–4.34). Mediation analysis revealed that depression mediated 2% (1.68%; 95% CI 0.23%–3.14%; p = 0.024) of the association between suicide bereavement and suicide in partners when using bereaved controls.

Depression is a partial mediator of the association between suicide bereavement and suicide. Efforts to prevent and optimize the treatment of depression in suicide-bereaved people could reduce their suicide risk. Our findings might be conservative because we did not include cases of depression diagnosed in primary care. Further work is needed to understand this and other mediators.