The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.

Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.

Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).

Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.

“Frailty” is associated with worse outcomes in adult cardiology. There is limited data on the associations between frailty and outcomes in paediatric cardiology. We aimed to define the prevalence of frailty and identify associations between frailty and neurodevelopmental and quality-of-life outcomes in high-risk paediatric cardiac populations.

This cross-sectional study included patients 4–18 years seen in a neurodevelopmental programme between 6/2017 and 11/2022. Demographic and clinical data were obtained from medical records. As part of the routine care, physical therapy assessment and neurocognitive, psychosocial, adaptive functioning, and quality-of-life surveys were administered. Social determinants of health were assessed by insurance status and Childhood Opportunity Index. Frailty was defined as the abnormality in 3 of 5 categories: body composition, weakness, slowness, physical activity, and exhaustion. Chi-Square, Student t, and Wilcoxon Rank Sum tests were used to assess differences between frail and non-frail groups.

Of the 270 patients, 101 (37%) met the frailty criteria. Frailty was not associated with social determinants of health, cardiac diagnosis, genetic syndrome, number of cardiac surgeries, or history of clinical complications. Frail patients were more likely to be older (p = 0.004) and have neurocognitive (p = 0.024), emotional (p = 0.003), social (p < 0.001), motor (p < 0.001), and adaptive dysfunction (p < 0.001) and lower quality of life (p = 0.029).

Frailty is common in school-aged patients with cardiac disease and is associated with adverse neurocognitive, psychosocial, motor, and adaptive outcomes and worse quality of life. Risk stratification for frailty may be a critical evaluation and screening element of high-risk cardiac patients in neurodevelopmental programmes.

Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

Haemolysis is developing prominence in the setting of supporting increasingly complex children with heart failure with a ventricular assist device. The goal of this study is to better characterise haemolysis and its implications in children supported with pulsatile ventricular assist devices.

This is a single-centre retrospective review of 44 children who were supported by Berlin Heart EXCOR between January 2006 and June 2020. Patients were divided into major haemolysers and non-major haemolysers. Major haemolysers were defined as patients with lactate dehydrogenase > 500U/L (2.5x the upper limits of normal) with either total bilirubin > 2mg/dL (with predominantly indirect hyperbilirubinemia) or anaemia out of proportion to the clinical scenario more than three days following implantation of the ventricular assist device(s). Patient demographics, ventricular assist device factors, and outcomes, including end-organ function and mortality, were compared between major haemolysers and non-major haemolysers.

Forty-four patients supported by the Berlin EXCOR were included in the analytic cohort of the study: 27 major haemolysers and 17 non-major haemolysers. Major haemolysis was more common in those supported with single-ventricle ventricular assist device (i.e., VAD in the context of functionally univentricular anatomy) compared to those with biventricular hearts, p = 0.01. There were no patients with an isolated left ventricular assist device or isolated right ventricular assist device in our analytic cohort of 44 patients. Of the 19 patients with single-ventricle ventricular assist device, 84% (16/19) were major haemolysers. Of the 25 patients with a biventricular assist device, 44% (11/25) were major haemolysers. Major haemolysers and non-major haemolysers had a body surface area of 0.28 and 0.40, respectively (p = 0.01). Overall, survival to discharge from the hospital was 66% (n = 29/44). Survival to discharge from the hospital was 52% (14/27) in major haemolysers versus 88% (15/17) in non-major haemolysers, p = 0.02. Only 3 of the 27 with major haemolysis had severe haemolysis, that is, lactate dehydrogenase > 2000 and bilirubin above 10. Non-major haemolysers had a better improvement in creatinine clearance during ventricular assist device support, p < 0.0001. (During the same era of this study, 22 patients who were supported with Berlin Heart were excluded from the analytic cohort because they did not have any recorded measurement of lactate dehydrogenase. Seventeen of these 22 patients had no clinical evidence of haemolysis. Survival to discharge from the hospital in this excluded cohort was 86% [19/22].)

Major haemolysis in patients with pulsatile ventricular assist device is more likely with single-ventricle ventricular assist device support and smaller body surface area.

Stress, a major risk factor for mental health problems, is influenced by hormonal fluctuations from the menstrual cycle and hormonal oral contraceptives (OC). Despite widespread use, the impact of hormonal intrauterine devices (IUDs) on stress is limited to one study.

This study examines psychoendocrine stress responses in women using IUDs, OCs and women with a natural, regular menstrual cycle (NC) to better understand how endogenous and exogenous hormones influence stress.

Using a repeated-measures design, we investigated stress responses in IUD and OC users and NC women. The Maastricht Acute Stress Task and its control task were applied twice within 4 months to assess subjective, endocrine and physiological stress correlates. Detailed endogenous and exogenous hormonal profiles were obtained, and women completed a 7-day diary (via ecological momentary assessment) after each appointment.

Based on subjective, physiological and cortisol responses, stress induction was successful in all groups. IUD users reported higher subjective stress, negative affect and anxiety and lower positive affect compared to NC women. OC users exhibited a blunted cortisol response and higher heart rate but reported less acute stress and negative emotions than the other groups in the 7-day diary. Oestradiol and progesterone were suppressed in OC and IUD users compared with NC women. Progesterone, testosterone and oestradiol were differently associated with skin conductance, socio-emotional stress and negative affect.

IUD and OC use distinctly affect stress response, possibly because of their diverging metabolic pathways and hormone levels. IUD users showed higher emotional reactivity to stress in both lab and daily life, while OCs influenced physiological correlates. These findings highlight that exogenous hormone administration, previously thought to have limited systemic effects, affects women’s psychological well-being, underscoring the need for further research into stress-related disorders among women using hormonal contraceptives.

It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Functional Somatic Disorders (FSD) and Internalizing Psychiatric Disorders (IPD) are frequently comorbid and likely share familial/genetic risk factors.

We performed a Common Factor Multivariate Analysis of 2 FSDs, Fibromyalgia (FM) and Irritable Bowel Syndrome (IBS), and two IPDs, Major Depression (MD) and Anxiety Disorders (AD), in five kinds of Swedish female–female relative pairs: monozygotic (n = 8,052) dizygotic (n = 7216), full siblings (n = 712,762), half-siblings reared together (n = 23,623), and half-siblings reared apart (n = 53,873). Model fitting was by full information maximum likelihood using OpenMx.

The best-fit model included genetic, shared environmental, and unique environmental factors. The common factor, ~50% heritable with a small shared environmental effect, loaded more strongly on the two IPDs (~0.80) than the 2 FSDs (0.40). Disorder-specific genetic effects were larger for the 2 FSDs (~0.30) than the 2 IPDs (~0.03). Estimated genetic correlations were high for MD and AD (+0.91), moderate between IBS and IPDs (+0.62), and intermediate between FM and MD (+0.54), FM and AD (+0.28), and FM and IBS (+0.38). Shared environmental influences on all disorders were present but small.

In women, FSDs and IPDs shared a moderate proportion of their genetic risk factors, greater for IBS than for FM. However, the genetic sharing between IBS and FM was less than between MD and AD, suggesting that FSDs do not form a highly genetically coherent group of disorders. The shared environment made a modest contribution to the familial aggregation of FSDs and IPDs.