The impact of depression on brain aging remains unclear, but both have been linked to stressful life events. Shared biological pathways may underlie structural brain changes. Clarifying these relationships could advance understanding of underlying mechanisms and inform treatment approaches.

Structural MRI scans of 190 participants (controls, n = 110, clinically diagnosed with major depressive disorder [MDD], n = 80), from the REDEEM dataset, were input into three pretrained brain age prediction models: brainageR, DeepBrainNet, and pyment. Prediction accuracy was compared in controls to identify the optimal model. DeepBrainNet demonstrated the highest accuracy and was selected for subsequent analysis. Brain-predicted age difference (brain-PAD) was calculated as predicted age minus chronological age. Linear regression examined the effects of MDD diagnosis, childhood maltreatment, and cortisol awakening response on brain-PAD.

Depressed participants reported greater childhood maltreatment but a similar cortisol awakening response. An Age × Group interaction (β = 0.34, 95% CI: 0.15–0.53, p < 0.001) indicated older adults with MDD exhibited greater positive deviations from normative brain age predictions, suggesting nonuniform brain aging across the lifespan. Cortisol awakening response showed a negative association with brain-PAD (β = −0.01, 95% CI: −0.01 to −0.00, p = 0.041), indicating higher HPA-axis reactivity was linked to younger-appearing brains. Females showed lower brain-PAD than males, reflecting younger-appearing brains.

MDD was associated with age-dependent differences in brain-PAD. The protective association between cortisol awakening response and brain age highlights the importance of integrating stress biomarkers to better understand neural aging mechanisms in depression.

The rising global prevalence of pediatric mental health problems requires the identification of preventable factors underlying their development. This study assessed whether maternal adverse childhood experiences (ACEs) and pregnancy stress were intergenerationally associated with offspring mental health.

This study used data from 34 sites in the nationwide Environmental Influences on Child Health Outcomes Cohort. Eligible parent–child dyads (child age: 1.5–18 years) provided data on at least one measure of maternal stress and at least one measure of child mental health. Study aims were evaluated using regression analyses, including interaction tests to determine potential effect modifiers.

Participants were organized into three subsamples with data on (1) maternal ACEs (N = 2,906), (2) perceived prenatal stress (N = 4,441), and (3) both stress exposures (N = 834). After adjusting for confounders, maternal ACEs and prenatal stress were significantly associated with child mental health problems (B = 2.53 [95% confidence interval [CI]: 2.09, 2.96], p < 0.0001 and B = 2.36 [95% CI: 2.03, 2.68], p < 0.0001, respectively). Among participants with data on both stress exposures, maternal ACEs (B = 1.72, 95% CI: [0.96, 2.48], p < 0.0001) and prenatal stress (B = 2.05, 95% CI: [1.29, 2.80], p < 0.0001) were independently associated with child mental health problems. Neither maternal ACEs nor child sex modified the association between prenatal stress and child mental health problems.

Maternal exposure to ACEs and pregnancy stress were associated with the development of child mental health problems. These findings highlight the need for policies and interventions that mitigate exposure to adversity and protect pregnant individuals and their children from the intergenerational transmission of mental health problems.

Evaluate impact of COVID-19 prevention training with video-based feedback on nursing home (NH) staff safety behaviors.

Public health intervention

Twelve NHs in Orange County, California, 6/2020-4/2022

NHs received direct-to-staff COVID-19 prevention training and weekly feedback reports with video montages about hand hygiene, mask-wearing, and mask/face-touching. One-hour periods of recorded streaming video from common areas (breakroom, hallway, nursing station, entryway) were sampled randomly across days of the week and nursing shifts for safe behavior. Multivariable models assessed the intervention impact.

Video auditing encompassed 182,803 staff opportunities for safe behavior. Hand hygiene errors improved from first (67.0%) to last (35.7%) months of the intervention, decreasing 7.6% per month (OR = 0.92, 95% CI = 0.92–0.93, P < 0.001); masking errors improved from first (10.3 %) to last (6.6%) months of the intervention, decreasing 2.3% per month (OR = 0.98, 95% CI = 0.97–0.99, P < 0.001); face/mask touching improved from first (30.0%) to last (10.6%) months of the intervention, decreasing 2.5% per month (OR = 0.98, 95% CI = 0.97–0.98, P < 0.001). Hand hygiene errors were most common in entryways and on weekends, with similar rates across shifts. Masking errors and face/mask touching errors were most common in breakrooms, with the latter occurring most commonly during the day (7A.M.–3P.M.) shift, with similar rates across weekdays/weekends. Error reductions were seen across camera locations, days of the week, and nursing shifts, suggesting a widespread benefit within participating NHs.

Direct-to-staff training with video-based feedback was temporally associated with improved hand hygiene, masking, and face/mask-touching behaviors among NH staff during the COVID-19 pandemic.

Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.

Compassionate Cities are a novel approach to health-promotive palliative care that uses a population-based approach to promote health and encourage its citizens to act with confidence to help others during death, dying, or bereavement. This study aimed to provide a critical account of how the leaders of a Compassionate City adopted the initiative and how they experienced its development and implementation.

An interpretative qualitative case study was conducted in a newly established Compassionate City in the UK. Data was collected using in-depth interviews, documentary analysis, and non-participatory observations. Reflective thematic analysis was used to analyze the contents of the multiple resources.

Five observations, 4 document analyses, and 11 interviews with members of the Compassionate City steering committee were conducted. We identified 4 themes: right model, right people, in the right place, at the right time; building a network of organizations and individuals; building sustainable community capacity to deal with grief, loss, and bereavement; and, embedding and sustaining the Compassionate City initiative. The study also found that cross-cutting factors such as leadership, visibility of work, evaluation, communication, and funding influenced and shaped the key themes when developing and implementing the Compassionate City.

This study provides broad insight into the key actions taken by the leaders of a Compassionate City aiming to improve the end-of-life experience of its citizens. We highlight the many challenges and complexities faced by the leaders when translating the concepts of Compassionate Cities into practice and identify key elements to consider for the successful implementation of future initiatives.

Class III obesity is associated with increased risk for cognitive impairment. Though hypothesized to be partially attributable to sedentary time (ST), past research examining the association between ST and cognitive function has produced mixed findings. One possible explanation is that studies do not typically account for the highly correlated and almost inverse relationship between ST and light intensity physical activity (LPA), such that ST displaces time engaging in LPA. Therefore, we aimed to evaluate whether: (1) higher ST-to-LPA time ratio associates with poorer performance across multiple cognitive domains in patients with Class III obesity seeking bariatric surgery; and (2) the associations differ by sex.

Participants (N = 121, 21-65 years of age, BMI > 40 kg/m2) scheduled for either Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy (SG) completed the NIH Toolbox, a computerized neuropsychological assessment battery and wore a waist-mounted ActiGraph monitor during waking hours for 7 days to measure minutes/day spent in ST, LPA, and moderate-to-vigorous physical activity (MVPA). A ratio of time spent in ST-to-LPA was calculated by dividing the percentage of daily wear time spent in sedentary behavior (SB) by the percentage of daily wear time spent in LPA.

On average, participants (mean age = 43.22 years old and BMI = 45.83 kg/m2) wore the accelerometer for 909±176 minutes/day and spent 642±174 minutes/day in ST, 254±79 minutes/day in LPA, and 14±13 minutes/day in MVPA. Mean daily ST-to-LPA time ratio was 2.81 ± 1.3 (0.73-7.11). Overall, bivariate Pearson correlations found no significant relationships between LPA and cognitive performance on any of the NIH Toolbox subtests (r values = -.002 to -.158, all p values >.05). Additionally, bivariate Pearson correlations also found no significant relationships between daily ST-to-LPA time ratio and cognitive performance on any of the subtests (r values = .003 to .108, all p values >.05). However, higher ST-to-LPA was associated with lower scores on the Dimensional Change Card Sort Test in women (r = -.26, p = .01).

Results showed that participants’ mean daily time spent in ST was 2.5 times higher than that spent in LPA and a higher ratio of ST-to-LPA was associated with poorer set-shifting in women with Class III obesity. Future studies should look to clarify underlying mechanisms, particularly studies examining possible sex differences in the cognitive benefits of PA. Similarly, intervention studies are also needed to determine if increasing LPA levels for individuals with Class III obesity would lead to improved cognitive performance by means of reducing ST.

Deficits in cognitive ability are common among patients with schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB) was designed to assess cognitive ability in studies of patients diagnosed with schizophrenia and has demonstrated high test-retest reliability with minimal practice effects, even in multi-site trials. However, given the motivational challenges associated with schizophrenia, it is unknown whether performance on MCCB tasks affects performance at later stages of testing. The goal of this study was to determine whether there are differences between people with and without schizophrenia in how their performance on individual MCCB tasks influences their performance throughout the battery.

The sample comprised 92 total participants including 49 cognitively healthy comparison participants and 43 outpatients diagnosed with schizophrenia. The mean age of participants was 44.2 years (SD = 12.0, range 21–69) and 61% identified as male. The Trail Making Test, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning Test – Revised, Letter-Number Span, and Category Fluency from the MCCB were administered in the same order at 2 different sites and studies from 2016–2022. The autocorrelation between t-scores for task scores within each participant was computed and then compared between control and outpatient participants to determine if there are differences between groups. Group mean t-scores for each task were also compared between groups.

We found no significant difference in autocorrelations across MCCB tasks between healthy comparison participants and outpatients. However, mean performance in all tasks was lower for the outpatient group than for the healthy comparison group. None of the tasks used stood out as having significantly lower mean scores than other tasks for either group.

Our findings suggest that performance on individual MCCB tasks do not affect performance throughout the battery differently between the healthy comparison group and outpatients. This suggests that participants with schizophrenia are not particularly reactive to past performance on MCCB tasks. Additionally, this finding further supports use of the MCCB in this population. Further research is needed to determine whether subgroups of patients and/or different batteries of measures show different patterns of reactivity.

Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.

To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.

Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.

Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).

The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.