Prenatal maternal stress is a known risk factor for later emotional problems, yet not all exposed offspring develop psychopathology. Executive functioning and prefrontal cortex structure and activity may buffer these effects, but it remains unclear whether genetic predispositions in these domains moderate associations with adolescent internalizing symptoms.

We examined 3,111 adolescents (1,881 females, 1,230 males). Prenatal stress was measured via a cumulative index across four domains. Internalizing symptoms were self-reported at ages 14 and 16. Genetic predisposition for executive functioning was indexed using a polygenic score (PGS) derived from adult samples, applied here to estimate genetic predisposition for executive functioning in adolescence. We also estimated a prefrontal cortex PGS based on cortical thickness and activation in six prefrontal regions, with a composite index derived from the first principal axis summarizing these measures.

Higher prenatal stress was significantly associated with more internalizing symptoms in adolescence. Female sex and maternal genetic risk for internalizing symptoms were also associated with higher symptom levels. Neither genetic disposition for executive functioning nor prefrontal cortex moderated this association overall. However, a weak interaction emerged at age 16, indicating that a genetic disposition for higher executive functioning was associated with greater internalizing symptoms under high stress exposure.

Prenatal maternal stress predicted increased adolescent internalizing symptoms, with limited evidence for moderation by genetic predisposition for executive functioning. Higher genetic potential for executive functioning may confer increased sensitivity to early stress under certain developmental conditions.

The high comorbidity between mental and cardiovascular diseases is widely recognized, but the underlying mechanisms are not yet well understood. We investigated the familial coaggregation and shared genetic loading between these diseases.

Using claims data from Taiwan’s universal health insurance program, we identified cohorts of 4,513,509 individuals with parental information and 3,330,181 with full-sibling information born between 1970 and 1999, and followed up until 2020. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. Multiple logistic regression models were used to estimate the association of parental history, full-sibling history, and polygenic risk scores (PRSs) for severe mental illnesses (schizophrenia, bipolar disorder, major depressive disorder [MDD]) with the risk of myocardial infarction, stroke, peripheral arterial disease (PAD), and heart failure.

Individuals with a parental history of schizophrenia, bipolar disorder, or MDD were more likely to have stroke and PAD. Coaggregation in full-siblings was observed for MDD with myocardial infarction and heart failure, bipolar disorders with stroke, and schizophrenia with PAD. The PAD risk increased with more relatives affected by MDD; the magnitude of association was larger when both parents were affected than when either parent was affected, and when there were two affected siblings than in those with only one. MDD PRS was positively associated with the risk of myocardial infarction and PAD.

This study revealed familial coaggregation between mental and cardiovascular diseases, and shared polygenic liability of MDD with cardiovascular diseases. Our findings suggest the potential benefit of family-based integrated screening and preventive strategies.

The relationship between frailty, self-efficacy, and advance care planning (ACP) remains unclear in Asia. This study examined how frailty status relates to decisional self-efficacy, ACP engagement, and advance directive completion among older adults receiving home healthcare in Taiwan.

A cross-sectional analysis was conducted using baseline data from a nationwide cohort in Taiwan. Participants (N = 358) were categorized by Clinical Frailty Scale (CFS): mildly frail (CFS 4–5, n = 60), moderately frail (CFS 6, n = 83), severely frail (CFS 7, n = 147), and very severely frail (CFS 8–9, n = 68). ACP engagement and decision-making self-efficacy were assessed using Likert scales.

Patients with greater frailty had lower odds of high decisional self-efficacy (CFS: 8–9: odds ratio [OR] = 0.38, 95% confidence interval [CI] = 0.14–1.07) but higher odds of ACP engagement (CFS: 6: OR = 3.38, 95% CI = 1.40–8.17; CFS: 7: OR = 2.52, 95% CI = 1.08–5.89) compared with mildly frail individuals. However, this increase did not extend linearly to the very severely frail group. Advance directive completion remained low across all frailty levels (4.8–10.0%) and was not significantly associated with frailty status.

Frailty was associated with lower decisional self-efficacy but higher readiness for ACP, revealing a divergence between perceived confidence and planning motivation. Despite greater engagement, advance directive completion remained low. Stage-sensitive, values-based approaches may help bridge the gap between intention and documentation across the frailty spectrum.

Cognitive dysfunction is a core feature of major depressive disorder. During transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD), the temporal relationship between symptom changes and cognitive performance remains unclear. We examined depressive symptoms and cognitive trajectories during TMS and tested whether time-varying cognitive change was associated with symptom trajectories.

This retrospective naturalistic study included 89 patients with TRD who completed 20 sessions of left dorsolateral prefrontal cortex TMS (high-frequency repetitive TMS or intermittent theta-burst stimulation). Depression severity (Hamilton Depression Rating Scale [HAMD-17]) and computerized attentional control measures from the Test of Attentional Performance were assessed at baseline, day 10, and day 20. Generalized estimating equations examined time effects and time-adjusted symptom-cognition associations. Exploratory analyses evaluated whether early cognitive change was associated with subsequent symptom improvement. Multiple comparisons were controlled.

Depressive symptoms decreased significantly (p < 0.001), with response and remission rates of 65.2% and 51.7%. Several attentional indices showed significant time effects; however, after false discovery rate correction, only visual divided-attention commission errors were independently associated with depressive severity beyond time effects. Person-mean centering indicated that this association was driven by within-person change (B = 0.209, p < 0.001), not between-person differences. Greater early reduction in visual divided-attention commission errors was associated with larger overall symptom improvement (B = 0.172, p = 0.016).

Within-person changes in divided attention tracked depressive symptom trajectories during TMS. Attentional control measures may therefore help track symptom-cognition dynamics during TMS in real-world clinical settings.

Although home is frequently the preferred place of death, little is known regarding how home healthcare (HHC) influences this outcome for people with dementia (PWD), particularly within Asian contexts. This study investigates the impact of HHC and its 2016 “Integrated Home-Based Medical Care” reform on home death in Taiwan, explicitly accounting for the cultural phenomenon of “impending death discharge.”

This nationwide retrospective cohort study utilized Taiwan’s National Health Insurance Research Database. We identified PWD decedents from 2011 to 2022 and conducted a nested case–control analysis. Cases (home deaths) and controls (hospital deaths) were matched 1:1 using propensity scores to balance demographics and health status. HHC models included pre-2016 primary HHC, post-2016 primary HHC, and the reformed “HBPC Plus” (Home-Based Primary Care Plus). The outcome was adjusted to include patients discharged terminally to die at home, reflecting distinctive cultural practices.

Among 209,468 decedents, 95,594 were selected after matching. Overall, HHC use was associated with higher odds of home death (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.13–1.21). The reformed HBPC Plus program showed the strongest association compared to pre-2016 primary HHC (aOR: 1.63; 95% CI: 1.34–1.98). Crucially, this association strengthened further when accounting for impending death discharge (aOR: 1.82; 95% CI: 1.40–2.35). Higher visit frequency and services from hospital-based teams were also significantly linked to home death.

HHC significantly increases the likelihood of home death among PWD in culturally influenced contexts. The 2016 reform, particularly the HBPC Plus program, proved highly effective. Policy components like flexible visit frequencies and enhanced hospital–physician coordination appear vital for supporting end-of-life care at home, offering key insights for policy planning in aging societies.

Subcortical nuclei – including the thalamus, basal ganglia, and hippocampus-amygdala complex – are key regions in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). While cortical–subcortical connectivity is well studied, fine intra- and inter-subcortical patterns are less known. This study aimed to identify shared and distinct functional connectivity alterations across SZ, BD, and MDD using a high-resolution subcortical atlas.

Resting-state functional magnetic resonance imaging data from 800 participants (200 per group: SZ, BD, MDD, and healthy controls) in a single-site cohort were analyzed. Subcortical structures were parcellated into 27 regions per hemisphere – thalamus (8 regions), hippocampus (5 regions), amygdala (2 regions), and striatum (12 regions) – based on the a priori atlas. Pairwise functional connectivity among the 54 regions was computed for each participant, and group differences were assessed using general linear models.

Patients with SZ exhibited significantly reduced intra-thalamic connectivity and increased intra-striatal connectivity, as well as enhanced connectivity between the thalamus, striatum, and limbic regions. Patients with BD showed reduced intra-thalamic and intra-striatal connectivity, along with decreased thalamus–amygdala and thalamus–striatum connectivity. In MDD, the predominant finding was reduced intra-limbic connectivity, accompanied by mild reductions in intra-thalamic and striatum–limbic connectivity.

The results suggest that intra-thalamic hypoconnectivity appears common to SZ, BD, and MDD, with graded degrees of severity. In contrast, distinct alterations in intra-striatal and striatum–limbic connectivity may differentiate mood disorders from SZ. These shared and disorder-specific subcortical connectivity patterns enhance the understanding of psychiatric neurobiology and may guide the development of targeted, disorder-tailored interventions.

Studies have shown that klotho, a neuroprotective protein, plays a crucial role in neurodevelopment. However, its association with attention-deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder, remains uncertain.

To elucidate klotho levels in adolescents with ADHD and to clarify its association with executive function.

The present study enrolled 92 adolescents (mean approximate age 14 years) diagnosed with ADHD and 80 age-matched healthy adolescents. All participants had their klotho levels measured and underwent the Wisconsin Card Sorting Test (WCST); their parents fulfilled the Swanson, Nolan and Pelham IV (SNAP-IV) scale and the Child Behavior Checklist-Dysregulation Profile (CBCL-DP).

Results from generalised linear models (GLMs), with adjustments for age, gender, body mass index, clinical symptoms (SNAP-IV and CBCL-DP scores) and ADHD medication use, indicated that adolescents with ADHD had significantly lower klotho levels (P = 0.044) and performed worse on WCST (P = 0.027) compared with healthy adolescents. The GLMs further indicated a negative association between klotho levels and the percentage of non-perseverative errors on WCST (P = 0.002).

Klotho may serve as a novel biomarker of ADHD and play a key role in ADHD-related executive dysfunction.

Adult major depression (MDD) studies implicate reward- and control-network dysconnectivity in suicidality, but it is unclear whether analogous alterations characterize adolescents, whose neural systems are still maturing.

Resting-state fMRI was obtained from 102 adolescents (12–17 years): 21 MDD with suicidal ideation (SI), 33 MDD without SI, and 48 matched healthy controls. Seed-based analyses targeted bilateral nucleus accumbens (NAc), ventral tegmental area (VTA), and bilateral dorsolateral prefrontal cortex (DLPFC).

Between-group effects were specific to NAc circuitry. Adolescents with SI showed reduced coupling of the left NAc with the left superior parietal lobule (BA7) versus controls, and diminished connectivity between the right NAc and right frontal pole (BA47) versus depressed peers without SI. No significant differences emerged for DLPFC- or VTA-seeded connectivity.

The identified functional dysconnectivities in reward-related circuits, particularly the FCs between the NAc and both the frontal pole and superior parietal lobule, may be implicated in the manifestation of suicidality among adolescents with MD. However, the lack of significant associations for DLPFC- and VTA-seeded FC in adolescent MDSI requires further elucidation.

Significant changes in Taiwan’s psychiatric services over recent decades include expansion of community-based clinics and implementation of the Schizophrenia Pay-for-Performance programme.

This study aimed to assess the trend of the quality of healthcare for individuals with schizophrenia, using various indicators of the treatment process and outcomes between 2010 and 2019.

Individuals with schizophrenia were identified using Taiwan’s National Health Insurance claims database. The quality of healthcare for individuals with schizophrenia was assessed using treatment process and outcome indicators, including antipsychotic types, medication adherence, daily dose for antipsychotics and concurrent use of other psychotropic agents. Outcome indicators included all-cause mortality, suicide deaths, psychiatric hospitalisation, emergency department visits and employment status.

Antipsychotic medication usage has shifted towards second-generation antipsychotics (SGAs) and long-acting injectable antipsychotics (LAIs), with declines in first-generation antipsychotics. The percentage of medication adherence declined, while that of individuals with an adequate daily dose increased. Concurrently, anticholinergic and benzodiazepine use decreased while antidepressant and mood stabiliser use increased. Outcome indicators showed no significant change in all-cause mortality or suicide rates over time, but there were reductions in psychiatric hospitalisations and emergency department visits. Employment rates increased overall, particularly in urban areas.

The quality of healthcare for individuals with schizophrenia, as measured by treatment process and outcome indicators, improved alongside changes in Taiwan’s psychiatric services; however, causality cannot be inferred from our findings. Future research should evaluate the effectiveness of psychiatric service policies and continuously monitor healthcare quality to further enhance the lives of individuals with schizophrenia.

Internet addiction (IA) refers to excessive internet use that causes cognitive impairment or distress. Understanding the neurophysiological mechanisms underpinning IA is crucial for enabling an accurate diagnosis and informing treatment and prevention strategies. Despite the recent increase in studies examining the neurophysiological traits of IA, their findings often vary. To enhance the accuracy of identifying key neurophysiological characteristics of IA, this study used the phase lag index (PLI) and weighted PLI (WPLI) methods, which minimize volume conduction effects, to analyze the resting-state electroencephalography (EEG) functional connectivity. We further evaluated the reliability of the identified features for IA classification using various machine learning methods.

Ninety-two participants (42 with IA and 50 healthy controls (HCs)) were included. PLI and WPLI values for each participant were computed, and values exhibiting significant differences between the two groups were selected as features for the subsequent classification task.

Support vector machine (SVM) achieved an 83% accuracy rate using PLI features and an improved 86% accuracy rate using WPLI features. t-test results showed analogous topographical patterns for both the WPLI and PLI. Numerous connections were identified within the delta and gamma frequency bands that exhibited significant differences between the two groups, with the IA group manifesting an elevated level of phase synchronization.

Functional connectivity analysis and machine learning algorithms can jointly distinguish participants with IA from HCs based on EEG data. PLI and WPLI have substantial potential as biomarkers for identifying the neurophysiological traits of IA.