Schizophrenia is a complex and heterogeneous syndrome with high clinical and biological stratification. Identifying distinctive subtypes can improve diagnostic accuracy and help precise therapy. A key challenge for schizophrenia subtyping is understanding the subtype-specific biological underpinnings of clinical heterogeneity. This study aimed to investigate if the machine learning (ML)-based neuroanatomical and symptomatic subtypes of schizophrenia are associated.

A total of 314 schizophrenia patients and 257 healthy controls from four sites were recruited. Gray matter volume (GMV) and Positive and Negative Syndrome Scale (PANSS) scores were employed to recognize schizophrenia neuroanatomical and symptomatic subtypes using K-means and hierarchical methods, respectively.

Patients with ML-based neuroanatomical subtype-1 had focally increased GMV, and subtype-2 had widespread reduced GMV than the healthy controls based on either K-means or Hierarchical methods. In contrast, patients with symptomatic subtype-1 had severe PANSS scores than subtype-2. No differences in PANSS scores were shown between the two neuroanatomical subtypes; similarly, no GMV differences were found between the two symptomatic subtypes. Cohen’s Kappa test further demonstrated an apparent dissociation between the ML-based neuroanatomical and symptomatic subtypes (P > 0.05). The dissociation patterns were validated in four independent sites with diverse disease progressions (chronic vs. first episodes) and ancestors (Chinese vs. Western).

These findings revealed a replicable dissociation between ML-based neuroanatomical and symptomatic subtypes of schizophrenia, which provides a new viewpoint toward understanding the heterogeneity of schizophrenia.

There is increasing research examining excess mortality in people with bipolar disorder using life expectancy and related measures, which quantify the disease impact on survival. However, there has been no meta-analysis to date summarising existing data on life expectancy in those with bipolar disorder.

To systematically review and quantitatively synthesise estimates of life expectancy and years of potential life lost (YPLL) in people with bipolar disorder.

We searched Embase, Medline, PsycINFO and Web of Science databases up to 31 March 2021. We generated pooled life expectancy using random-effects models, and derived YPLL summary estimate by calculating averaged values weighted by sample size of individual studies. Subgroup analyses were conducted for gender, geographical region, study period, a given age (set-age) for lifespan estimation and causes of death. The study was registered with PROSPERO (CRD42021241705).

Eleven and 13 studies were included in the review for life expectancy (n = 96 601) and YPLL (n = 128 989), respectively. Pooled life expectancy was 66.88 years (95% CI 64.47–69.28; I2 = 99.9%, P < 0.001), was higher in women than men (70.51 (95% CI 68.61–72.41) v. 64.59 (95% CI 61.16–68.03); z = 2.00, P = 0.003) and was lowest in Africa. Weighted average YPLL was 12.89 years (95% CI 12.72–13.07), and was greatest in Africa. More YPLL was observed when lifespan was estimated at birth than at other set-age. YPLLs attributable to natural and unnatural deaths were 5.94 years (95% CI 5.81–6.07) and 5.69 years (95% CI 5.59–5.79), respectively.

Bipolar disorder is associated with substantially shortened life expectancy. Implementation of multilevel, targeted interventions is urgently needed to reduce this mortality gap.

Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention.

360 psychosis patients aged 26–55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years.

Compared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001–0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004–0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year.

Specialized EI treatment for psychosis patients aged 26–55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.

The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics.

We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia).

We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days.

Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.

Schizophrenia is a longstanding condition and most patients experience multiple relapse in the course of the condition. High expressed emotion (HEE) has been found to be a predictor of relapse. This meta-analysis and meta-regression examined the association of global EE and relapse specifically focusing on timing of relapse and EE domains.

Random-effects model was used to pool the effect estimates. Multiple random-effects meta-regression was used to compute the moderator analysis. Putative effect moderators including culture, EE measurements, age, length of condition and study quality were included.

Thirty-three prospective cohort studies comprising 2284 patients were included in the descriptive review and 30 studies were included for meta-analysis and meta-regression. Findings revealed that global HEE significantly predicted more on early relapse (⩽12 months) [OR 4.87 (95% CI 3.22–7.36)] than that on late relapse (>12 months) [OR 2.13 (95% CI 1.36–3.35)]. Higher level of critical comments (CC) significantly predicted relapse [OR 2.22 (95% CI 1.16–4.26)], whereas higher level of warmth significantly protected patients from relapse [OR 0.35 (95% CI 0.15–0.85)]. None of the moderators included significantly change the results.

These findings indicate that there is a dynamic interaction between EE-relapse association with time, and CC and warmth are the two important EE domains to influence relapse among patients with schizophrenia. Results also confirmed the foci of family interventions on reducing CC and improving warmth in relationship.

Schizophrenia patients have markedly elevated prevalence of diabetes compared with the general population. However, risk of mortality and diabetes-related complications among schizophrenia patients with co-occurring diabetes is understudied.

We investigated whether schizophrenia increased the risk of overall mortality, complications and post-complication mortality in people with diabetes.

This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68 682 patients with incident diabetes only between 2001 and 2016 in Hong Kong using a medical record database of public healthcare services. Association between schizophrenia and all-cause mortality was examined with a Cox proportional hazards model. Effect of schizophrenia on first-year complication occurrence following diabetes diagnosis and post-complication mortality rates were evaluated.

Schizophrenia was associated with increased all-cause mortality (adjusted hazards ratio [aHR] 1.11, 95% CI 1.05–1.18), particularly among men and older age groups. Schizophrenia patients with diabetes had higher metabolic complication rate (aHR 1.99, 95% CI 1.63–2.42), lower microvascular complication rate (aHR 0.75, 95% CI 0.65–0.86) and comparable macrovascular complication rate (aHR 0.93, 95% CI 0.85–1.03), relative to patients with diabetes only. Among patients with diabetes complications, schizophrenia was associated with elevated all-cause mortality after macrovascular (aHR 1.19, 95% CI 1.04–1.37) and microvascular (aHR 1.33, 95% CI 1.08–1.64) complications. Gender-stratified analyses revealed that a significant effect of schizophrenia on heightened post-complication mortality was observed in men only.

Schizophrenia patients with co-occurring diabetes are at increased risk of excess mortality, including post-complication mortality. Further research identifying effective interventions is warranted to optimise diabetes-related outcomes in this vulnerable population.

Little is known about poverty trends in people with severe mental illness (SMI) over a long time span, especially under conditions of fast socioeconomic development.

This study aims to unravel changes in household poverty levels among people with SMI in a fast-changing rural community in China.

Two mental health surveys, using ICD-10, were conducted in the same six townships of Xinjin county, Chengdu, China. A total of 711 and 1042 people with SMI identified in 1994 and 2015, respectively, participated in the study. The Foster-Greer-Thorbecke poverty index was adopted to measure the changes in household poverty. These changes were decomposed into effects of growth and equity using a static decomposition method. Factors associated with household poverty in 1994 and 2015 were examined and compared by regression analyses.

The proportion of poor households, as measured by the headcount ratio, increased significantly from 29.8% in 1994 to 39.5% in 2015. Decomposition showed that poverty in households containing people with SMI had worsened because of a redistribution effect. Factors associated with household poverty had also changed during the study period. The patient's age, ability to work and family size were of paramount significance in 2015.

This study shows that the levels of poverty faced by households containing people with SMI has become more pressing with China's fast socioeconomic development. It calls for further integration of mental health recovery and targeted antipoverty interventions for people with SMI as a development priority.

The relationship between the subtypes of psychotic experiences (PEs) and common mental health symptoms remains unclear. The current study aims to establish the 12-month prevalence of PEs in a representative sample of community-dwelling Chinese population in Hong Kong and explore the relationship of types of PEs and common mental health symptoms.

This is a population-based two-phase household survey of Chinese population in Hong Kong aged 16–75 (N = 5719) conducted between 2010 and 2013 and a 2-year follow-up study of PEs positive subjects (N = 152). PEs were measured with Psychosis Screening Questionnaire (PSQ) and subjects who endorsed any item on the PSQ without a clinical diagnosis of psychotic disorder were considered as PE-positive. Types of PEs were characterized using a number of PEs (single v. multiple) and latent class analysis. All PE-positive subjects were assessed with common mental health symptoms and suicidal ideations at baseline and 2-year follow-up. PE status was also assessed at 2-year follow-up.

The 12-month prevalence of PEs in Hong Kong was 2.7% with 21.1% had multiple PEs. Three latent classes of PEs were identified: hallucination, paranoia and mixed. Multiple PEs and hallucination latent class of PEs were associated with higher levels of common mental health symptoms. PE persistent rate at 2-year follow-up was 15.1%. Multiple PEs was associated with poorer mental health at 2-year follow-up.

Results highlighted the transient and heterogeneous nature of PEs, and that multiple PEs and hallucination subtype of PEs may be specific indices of poorer common mental health.

Negative affect (NA) has been suggested to be both an antecedent and a consequence of auditory verbal hallucinations (AVH). Furthermore, negative appraisals of voices have been theorized to contribute to the maintenance of AVH. Using the experience sampling method (ESM), this study examined the bi-directional relationship between NA and AVH, and the moderating effect of negative beliefs about voices.

Forty-seven patients diagnosed with schizophrenia spectrum disorders with frequent AVH completed a clinical interview, followed by ESM for 10 times a day over 6 days on an electronic device. Time-lagged analyses were conducted using multilevel regression modeling. Beliefs about voices were assessed at baseline.

A total of 1654 data points were obtained. NA predicted an increase in AVH in the subsequent moment, and AVH predicted an increase in NA in the subsequent moment. Baseline beliefs about voices as malevolent and omnipotent significantly strengthened the association between NA and AVH within the same moment. In addition, the belief of omnipotence was associated with more hallucinatory experiences in the moment following NA. However, beliefs about voices were not associated directly with momentary levels of NA or AVH.

Experiences of NA and AVH drove each other, forming a feedback loop that maintained the voices. The associations between NA and AVH, either within the same moment or across moments, were exacerbated by negative beliefs about voices. Our results suggest that affect-improving interventions may stop the feedback loop and reduce AVH frequency.

Findings from single-session online studies highlighted the potential of using anodal prefrontal transcranial direct current stimulation (tDCS) to enhance executive functions (EF) in the context of aging. However, tDCS must be executed as a multi-session offline intervention to ascertain its viability in this context. Relatedly, findings from multi-session studies remained inconclusive. To this end, we examined the effects of multi-session anodal prefrontal tDCS on EF in an intervention.

The intervention consisted of 15 sessions; in each, healthy older participants (Agemean = 66.7) received either 15 min of 1.5 mA tDCS (Ncompleted = 35) or sham stimulation (Ncompleted = 33) while performing EF training tasks. EF measures were assessed at baseline, post-intervention, and 1-month follow-up. Hierarchical linear models were used to examine the effect of tDCS on EF outcomes.

Both groups of participants did not differ significantly in side effect ratings and attendance. There were no significant tDCS-associated gains in any EF outcomes in the intervention.

Multi-session prefrontal tDCS did not lead to any significant gains in EF in the current intervention. More research is needed to optimize the use of tDCS before it can be effectively used to enhance EF among older adults.

An in-house self-held respiration monitoring device (SHRMD) was developed for providing deep inspiration breath hold (DIBH) radiotherapy. The use of SHRMD is evaluated in terms of reproducibility, stability and heart dose reduction.

Sixteen patients receiving radiotherapy of left breast cancer were planned for treatment with both a free breathing (FB) scan and a DIBH scan. Both FB and DIBH plans were generated for comparison of the heart, left anterior descending (LAD) artery and lung dose. All patients received their treatments with DIBH using SHRMD. Megavoltage cine images were acquired during treatments for evaluating the reproducibility and stability of treatment position using SHRMD.

Compared with FB plans, the maximum dose to the heart by DIBH technique with SHRMD was reduced by 29·9 ± 15·6%; and the maximum dose of the LAD artery was reduced by 41·6 ± 18·3%. The inter-fractional overall mean error was 0·01 cm and the intra-fractional overall mean error was 0·04 cm.

This study demonstrated the potential benefits of using the SHRMD for DIBH to reduce the heart and LAD dose. The patients were able to perform stable and reproducible DIBHs.