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Negative symptoms are an important symptom dimension in schizophrenia that are often least responsive to antipsychotic medications. We revisit the current practice of identifying ‘primary’ negative symptoms and suggest that its concept would benefit from a further elaboration of their timing of emergence in relation to the dynamic neurobiological changes to enhance their utility in clinical decision-making and research.
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.
Little is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia.
A three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12.
The MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement.
Our results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.
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 the trend and predictors of 21-year mortality and suicide patterns in persons with schizophrenia.
To explore the trend and predictors of 21-year mortality and suicide in persons with schizophrenia in rural China.
This longitudinal follow-up study included 510 persons with schizophrenia who were identified in a mental health survey of individuals (≥15 years old) in 1994 in six townships of Xinjin County, Chengdu, China, and followed up in three waves until 2015. Kaplan–Meier survival analysis and Cox hazard regressions were conducted.
Of the 510 participants, 196 died (38.4% mortality) between 1994 and 2015; 13.8% of the deaths (n = 27) were due to suicide. Life expectancy was lower for men than for women (50.6 v. 58.5 years). Males consistently showed higher rates of mortality and suicide than females. Older participants had higher mortality (hazard ratio HR = 1.03, 95% CI 1.01–1.05) but lower suicide rates (HR = 0.95, 95% CI 0.93–0.98) than their younger counterparts. Poor family attitudes were associated with all-cause mortality and death due to other causes; no previous hospital admission and a history of suicide attempts independently predicted death by suicide.
Our findings suggest there is a high mortality and suicide rate in persons with schizophrenia in rural China, with different predictive factors for mortality and suicide. It is important to develop culture-specific, demographically tailored and community-based mental healthcare and to strengthen family intervention to improve the long-term outcome of persons with schizophrenia.
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.
Little is known about long-term employment outcomes for patients with first-episode schizophrenia-spectrum (FES) disorders who received early intervention services.
We compared the 10-year employment trajectory of patients with FES who received early intervention services with those who received standard care. Factors differentiating the employment trajectories were explored.
Patients with FES (N = 145) who received early intervention services in Hong Kong between 1 July 2001 and 30 June 2002 were matched with those who entered standard care 1 year previously. We used hierarchical clustering analysis to explore the 10-year employment clusters for both groups. We used the mixed model test to compare cluster memberships and piecewise regression analysis to compare the employment trajectories of the two groups.
There were significantly more patients who received the early intervention service in the good employment cluster (early intervention: N = 98 [67.6%]; standard care: N = 76 [52.4%]; P = 0.009). In the poor employment cluster, there was a significant difference in the longitudinal pattern between early intervention and standard care for years 1–5 (P < 0.0001). The number of relapses during the first 3 years, months of full-time employment during the first year and years of education were significant in differentiating the clusters of the early intervention group.
Results suggest there was an overall long-term benefit of early intervention services on employment. However, the benefit was not sustained for all patients. Personalisation of the duration of the early intervention service with a focus on relapse prevention and early vocational reintegration should be considered for service enhancement.
Cognitive impairment is a core feature of schizophrenia and has been observed in both familial (FHR) and clinical high-risk (CHR) samples. Nonetheless, there is a paucity of research directly contrasting cognitive profiles in these two high-risk states and first-episode schizophrenia. This study aimed to compare cognitive functions in patients with first-episode schizophrenia-spectrum disorder (FES), their unaffected siblings (FHR), CHR individuals and healthy controls.
A standardized battery of cognitive assessments was administered to 69 FES patients, 71 help-seeking CHR individuals without family history of psychotic disorder, 50 FHR participants and 68 controls. FES and CHR participants were recruited from territory-wide early intervention service for psychosis in Hong Kong. CHR status was ascertained using Comprehensive Assessment of At-Risk Mental State.
Among four groups, FES patients displayed the largest global cognitive impairment and had medium-to-large deficits across all cognitive tests relative to controls. CHR and FHR participants significantly underperformed in most cognitive tests than controls. Among various cognitive tests, digit symbol coding demonstrated the greatest magnitude of impairment in FES and CHR groups compared with controls. No significant difference between two high-risk groups was observed in global cognition and all individual cognitive tests except digit symbol coding which showed greater deficits in CHR than in FHR participants.
Clinical and familial risk groups experienced largely comparable cognitive impairment that was intermediate between FES and controls. Digit symbol coding may have the greatest discriminant capacity in distinguishing FES and CHR from healthy controls, and between two high-risk samples.
Evidence indicates that the positive effects of 2-year early intervention services for psychosis are not maintained after service withdrawal. Optimal duration of early intervention in sustaining initial improved outcomes remains to be determined.
To examine the sustainability of the positive effects of an extended, 3-year, early intervention programme for patients with first-episode psychosis (FEP) after transition to standard care.
A total of 160 patients, who had received a 2-year early intervention programme for FEP, were enrolled to a 12-month randomised-controlled trial (ClinicalTrials.gov: NCT01202357) comparing a 1-year extension of the early intervention (3-year specialised treatment) with step-down care (2-year specialised treatment). Participants were followed up and reassessed 2 and 3 years after inclusion to the trial.
There were no significant differences between the treatment groups in outcomes on functioning, symptom severity and service use during the post-trial follow-up period.
The therapeutic benefits achieved by the extended, 3-year early intervention were not sustainable after termination of the specialised service.
Anxiety disorders are prevalent yet under-recognized in late life. We examined the prevalence of anxiety disorders in a representative sample of community dwelling older adults in Hong Kong.
Data on 1,158 non-demented respondents aged 60–75 years were extracted from the Hong Kong Mental Morbidity survey (HKMMS). Anxiety was assessed with the revised Clinical Interview Schedule (CIS-R).
One hundred and thirty-seven respondents (11.9%, 95% CI = 10–13.7%) had common mental disorders with a CIS-R score of 12 or above. 8% (95% CI = 6.5–9.6%) had anxiety, 2.2% (95% CI = 1.3–3%) had an anxiety disorder comorbid with depressive disorder, and 1.7% (95% CI = 1–2.5%) had depression. Anxious individuals were more likely to be females (χ2 = 25.3, p < 0.001), had higher chronic physical burden (t = −9.3, p < 0.001), lower SF-12 physical functioning score (t = 9.2, p < 0.001), and poorer delayed recall (t = 2.3, p = 0.022). The risk of anxiety was higher for females (OR 2.8, 95% C.I. 1.7–4.6, p < 0.001) and those with physical illnesses (OR 1.4, 95% C.I. 1.3–1.6, p < 0.001). The risk of anxiety disorders increased in those with disorders of cardiovascular (OR 1.9, 95% C.I. 1.2–2.9, p = 0.003), musculoskeletal (OR 2.0, 95% C.I. 1.5–2.7, p < 0.001), and genitourinary system (OR 2.0, 95% C.I. 1.3–3.2, p = 0.002).
The prevalence of anxiety disorders in Hong Kong older population was 8%. Female gender and those with poor physical health were at a greater risk of developing anxiety disorders. Our findings also suggested potential risk for early sign of memory impairment in cognitively healthy individuals with anxiety disorders.
The long-term outcome of never-treated patients with schizophrenia is
To compare the 14-year outcomes of never-treated and treated patients
with schizophrenia and to establish predictors for never being
All participants with schizophrenia (n = 510) in Xinjin,
Chengdu, China were identified in an epidemiological investigation of 123
572 people and followed up from 1994 to 2008.
The results showed that there were 30.6%, 25.0% and 20.4% of patients who
received no antipsychotic medication in 1994, 2004 and 2008 respectively.
Compared with treated patients, those who were never treated in 2008 were
significantly older, had significantly fewer family members, had higher
rates of homelessness, death from other causes, being unmarried, living
alone, being without a caregiver and poor family attitudes. Partial and
complete remission in treated patients (57.3%) was significantly higher
than that in the never-treated group (29.8%). Predictors of being in the
never-treated group in 2008 encompassed baseline never-treated status,
being without a caregiver and poor mental health status in 1994.
Many patients with schizophrenia still do not receive antipsychotic
medication in rural areas of China. The 14-year follow-up showed that
outcomes for the untreated group were worse. Community-based mental
healthcare, health insurance and family intervention are crucial for
earlier diagnosis, treatment and rehabilitation in the community.
Numerous early intervention services targeting young people with
psychosis have been established, based on the premise that reducing
treatment delay and providing intensive treatment in the initial phase of
psychosis can improve long-term outcome.
To establish the effect of extending a specialised early intervention
treatment for first-episode psychosis by 1 year.
A randomised, single-blind controlled trial (NCT01202357) compared a
1-year extension of specialised early intervention with step-down care in
patients who had all received a 2-year intensive early intervention
programme for first-episode psychosis.
Patients receiving an additional year of specialised intervention had
better outcomes in functioning, negative and depressive symptoms and
treatment default rate than those managed by step-down psychiatric
Extending the period of specialised early intervention is clinically
desirable but may not be feasible in lower-income countries.
Little is known about gender differences in the long-term outcomes of
people with schizophrenia living in the community.
To explore gender differences in the 14-year outcome of people with
schizophrenia in rural China.
A 14-year follow-up study among a 1994 cohort (n = 510)
of participants with schizophrenia was conducted in Xinjin County,
Chengdu, China. All participants and their informants were followed up in
2004 and 2008 using the Patients Follow-up Schedule.
Compared with female participants, male participants were significantly
younger, had significantly higher rates of mortality, suicide and
homelessness, and poorer family and social support. There was no
significant gender difference in Positive and Negative Syndrome Scale
scores, previous suicide attempts, those never treated, previous hospital
admission or inability to work. Longer duration of illness was associated
with functional decline and comparatively poorer family economic
The long-term outcomes of men with schizophrenia is worse than those of
women with the disorder in rural China. Higher mortality, suicide and
homelessness rates in men may contribute partly to the higher prevalence
of schizophrenia in women in China. Policies on social and family support
and gender-specific intervention strategies for improving long-term
outcomes should be developed for people with this disorder.
From a very deprived baseline, mental health services in Hong Kong have undergone some growth over the past decade. The number of inpatient beds for psychiatric treatment dropped by one-third, but the community mental health service expanded significantly. A number of low-resource phase-specific and age-specific treatment programmes were introduced, with promising initial results. However, there remain many challenges, including a serious shortage of well-trained mental health professionals. Much more investment in mental health workforce development is required to meet the service needs not only of today, but also of tomorrow.
Many people with schizophrenia remain untreated in the community.
Long-term mortality and suicidal behaviour among never-treated
individuals with schizophrenia in the community are unknown.
To explore 10-year mortality and suicidal behaviour among never-treated
individuals with schizophrenia.
We used data from a 10-year prospective follow-up study (1994–2004) among
people with schizophrenia in Xinjin County, Chengdu, China.
The mortality rate for never-treated individuals with schizophrenia was
2761 per 100 000 person-years during follow-up. There were no significant
differences of rates of suicide and all-cause mortality between
never-treated and treated individuals. The standardised mortality ratio
(SMR) for never-treated people was 10.4 (95% CI 7.2–15.2) and for treated
individuals 6.5 (95% CI 5.2–8.5). Compared with treated people,
never-treated individuals were more likely to be older, poorer, have a
longer duration of illness, marked symptoms and fewer family members.
The never-treated individuals have similar mortality to and a higher
proportion of marked symptoms than treated people, which may reflect the
poor outcome of the individuals without treatment. The higher rates of
mortality, homelessness and never being treated among people with
schizophrenia in low- and middle-income nations might challenge presumed
wisdom about schizophrenia outcomes in these countries.
Long-term mortality and the risk factors for premature death among
patients with schizophrenia living in rural communities are unknown.
To explore the 10-year mortality and its risk factors among patients with
We used data from a 10-year prospective follow-up study (1994–2004) of
mortality among people with schizophrenia, and death registration data
for Xinjin County, Chengdu, China.
The mortality rate was 2228 per 100 000 person-years during follow-up.
Both all-cause mortality and suicide rates were significantly greater in
male than in female patients. Age at illness onset (>45 years),
duration of illness (⩾10 years), age greater than 50 years, physical
illness, inability to work, male gender, and never having received
treatment were identified as independent predictors of increased
Higher mortality rates in male patients may contribute to the higher
prevalence of schizophrenia in women compared with men in China. The
findings of risk factors for mortality should be taken into account when
developing interventions to improve outcomes among people with
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