Abstract
Negative symptoms are prevalent in the prodromal and first-episode phases of psychosis and highly predictive of poor clinical outcomes (eg, liability for conversion and functioning). ...However, the latent structure of negative symptoms is unclear in the early phases of illness. Determining the latent structure of negative symptoms in early psychosis (EP) is of critical importance for early identification, prevention, and treatment efforts. In the current study, confirmatory factor analysis was used to evaluate latent structure in relation to 4 theoretically derived models: 1. a 1-factor model, 2. a 2-factor model with expression (EXP) and motivation and pleasure (MAP) factors, 3. a 5-factor model with separate factors for the 5 National Institute of Mental Health (NIMH) consensus development conference domains (blunted affect, alogia, anhedonia, avolition, and asociality), and 4. a hierarchical model with 2 second-order factors reflecting EXP and MAP, as well as 5 first-order factors reflecting the 5 consensus domains. Participants included 164 individuals at clinical high risk (CHR) who met the criteria for a prodromal syndrome and 377 EP patients who were rated on the Brief Negative Symptom Scale. Results indicated that the 1- and 2-factor models provided poor fit for the data. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model outperforming the hierarchical model. These findings suggest that similar to the chronic phase of schizophrenia, the latent structure of negative symptom is best conceptualized in relation to the 5 consensus domains in the CHR and EP populations. Implications for early identification, prevention, and treatment are discussed.
BackgroundThere 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.AimsTo systematically review and quantitatively synthesise estimates of life expectancy and years of potential life lost (YPLL) in people with bipolar disorder.MethodWe 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).ResultsEleven 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.ConclusionsBipolar disorder is associated with substantially shortened life expectancy. Implementation of multilevel, targeted interventions is urgently needed to reduce this mortality gap.
Oxford Nanopore sequencing can detect DNA methylations from ionic current signal of single molecules, offering a unique advantage over conventional methods. Additionally, adaptive sampling, a ...software-controlled enrichment method for targeted sequencing, allows reduced representation methylation sequencing that can be applied to CpG islands or imprinted regions. Here we present DeepMod2, a comprehensive deep-learning framework for methylation detection using ionic current signal from Nanopore sequencing. DeepMod2 implements both a bidirectional long short-term memory (BiLSTM) model and a Transformer model and can analyze POD5 and FAST5 signal files generated on R9 and R10 flowcells. Additionally, DeepMod2 can run efficiently on central processing unit (CPU) through model pruning and can infer epihaplotypes or haplotype-specific methylation calls from phased reads. We use multiple publicly available and newly generated datasets to evaluate the performance of DeepMod2 under varying scenarios. DeepMod2 has comparable performance to Guppy and Dorado, which are the current state-of-the-art methods from Oxford Nanopore Technologies that remain closed-source. Moreover, we show a high correlation (r = 0.96) between reduced representation and whole-genome Nanopore sequencing. In summary, DeepMod2 is an open-source tool that enables fast and accurate DNA methylation detection from whole-genome or adaptive sequencing data on a diverse range of flowcell types.
Psychiatric patients are susceptible to adverse mental health impacts during COVID-19, but complex interplays between psychopathology and pandemic-related variables remain elusive. This study aimed ...to investigate concomitant associations between psychopathological symptoms, psychological measures and COVID-19 related variables in Chinese psychiatric patients during the peak of fifth pandemic wave in Hong Kong.
We employed network analysis to investigate inter-relationships among psychopathological symptoms (including depression, anxiety, post-traumatic stress disorder-like PTSD-like symptoms, insomnia, psychotic symptoms), cognitive complaints, health-related quality of life, loneliness, resilience and selected pandemic-related factors in 415 psychiatric outpatients between 28 March and 8 April, 2022. Network comparisons between genders, diagnosis (common mental disorders CMD vs. severe mental disorders SMD), and history of contracting COVID-19 at fifth wave were performed as exploratory analyses.
Our results showed that anxiety represented the most central node in the network, as indicated by its highest node strength and expected influence, followed by depression and quality of life. Three comparatively strong connections between COVID-19 and psychopathological variables were observed including: fear of contagion and PTSD-like symptoms, COVID-19 stressor burden and PTSD-like symptoms, and COVID-19 stressor burden and insomnia. Network comparison tests revealed significant network structural difference between participants with history of contracting COVID-19 and those without, but showed no significant difference between genders as well as between CMD and SMD patients.
Our findings suggest the pivotal role of anxiety in psychopathology network of psychiatric patients amidst COVID-19. Pandemic-related variables are critically associated with trauma/stress and insomnia symptoms. Future research is required to elucidate potential network structural changes between pandemic and post-COVID periods.
Psychiatric patients are susceptible to adverse mental health outcome during COVID-19 pandemic, but its associated factors are understudied. This observational cross-sectional study aimed to ...comprehensively examine prevalence and correlates of psychological distress, in terms of depression, anxiety and post-traumatic-stress-disorder (PTSD)-like symptoms, among Chinese adult psychiatric outpatients amidst the peak of fifth COVID-19 wave in Hong-Kong.
A total of 415 patients (comprising 246 patients with common-mental-disorders CMD and 169 with severe-mental-disorders SMD) and 399 demographically-matched controls without mental disorders were assessed with self-rated questionnaires between 28-March and 8-April-2022, encompassing illness profile, mental health symptoms, psychosocial measures (loneliness, resilience, coping styles) and COVID-19 related factors. Univariate and multivariable logistic regression analyses were conducted to determine variables associated with moderate-to-severe depressive, anxiety and PTSD-like symptoms among psychiatric patients.
Our results showed that CMD patients had the greatest psychological distress relative to SMD patients and controls. Approximately 40-55% CMD patients and 25% SMD patients exhibited moderate-to-severe depression, anxiety and PTSD-like symptoms. Multivariable regression analyses revealed that female gender, lower educational attainment, single marital status, being housewife, more severe insomnia, psychotic-like symptoms and cognitive complaints, self-harm behavior, lower resilience, avoidance coping, never contracting COVID-19 infection, greater fear of contagion, and longer exposure to pandemic-related information were independently associated with depression, anxiety and/or PTSD-like symptoms in psychiatric patients.
Our results affirm increased vulnerability of psychiatric patients toward psychological distress during pandemic. An array of identified correlates facilitates early detection of high-risk psychiatric patients for targeted strategies to minimize pandemic-related negative psychological impact.
High levels of plasma marine n-3 fatty acids (n-3FAs) are associated with improved patient and graft survival in renal transplant recipients (RTRs). The aim of this study was to evaluate the utility ...of a new food frequency questionnaire (FFQ) to estimate marine n-3FA consumption in future epidemiological research.
We developed an FFQ with a simple design of 10 questions to assess intake of marine sources of n-3FAs. RTRs included in the recent ORENTRA trial (n = 132) completed the study FFQ at the baseline visit eight weeks after engraftment and at the end of study visit one year post-transplant. We measured the reference biomarker plasma phospholipid (PL) marine n-3FA levels by gas chromatography at the same time points to evaluate association and degree of agreement between FFQ based marine n-3FA consumption estimates and the biomarker.
The median plasma PL marine n-3FA level was 6.0 weight percentage (wt)% (interquartile range IQR 4.7 to 7.3) at baseline and 6.3 wt% (IQR 4.8 to 7.4) at end of study. Median FFQ based marine n-3FA consumption estimates were 22.8 g/month (IQR 13.0 to 34.0) at baseline and 20.3 g/month (IQR 14.5 to 32.3) at end of study. FFQ based marine n-3FA consumption estimates showed a moderate correlation with plasma PL marine n-3FA levels at baseline (Spearman's correlation coefficient rs = 0.43, p<0.001) and a stronger correlation at end of study (rs = 0.62, p<0.001). Bland Altman plots showed a reasonable degree of agreement between the two methods at both time points.
Marine n-3FA consumption estimates based on the FFQ showed a moderate correlation with the reference biomarker plasma PL marine n-3FA levels. The FFQ might be useful in epidemiological studies where resources are limited.
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.
Purpose
Schizophrenia is associated with increased premature mortality and physical morbidity. This study aimed to examine prevalence of pre-existing chronic physical diseases, and association ...between physical multimorbidity burden and mortality rates among patients with newly diagnosed schizophrenia.
Methods
This population-based cohort study investigated patients with first-recorded diagnosis of schizophrenia between January 2006 and December 2016, using territory-wide medical-record database of public healthcare service in Hong Kong. Physical morbidities were measured by Charlson Comorbidity Index (CCI), taking into consideration both number and severity of physical diseases, and were grouped into nine broad disease categories for analyses. Physical multimorbidity burden was stratified into three levels according to CCI of 0, 1 or ≥ 2. Cox proportional hazards regression models were used to examine associations of physical multimorbidity with mortality rates.
Results
Of the 13,945 patients, 8.6% (
n
= 1207) had pre-existing physical morbidity. Patients with physical morbidity exhibited elevated all-cause mortality rate relative to those without physical morbidity adjusted HR 2.38 (95% CI 2.04–2.77). Gastrointestinal/liver diseases, diabetes and cardiovascular diseases constituted the three most frequently diagnosed physical morbidities, whereas cancers displayed the highest all-cause mortality rate. An increase in physical multimorbidity burden was associated with increased all-cause mortality rate CCI = 1: 1.98 (1.64–2.40); CCI ≥ 2: 3.08 (2.51–3.77), CCI = 0 as reference.
Conclusion
Schizophrenia patients with pre-existing physical morbidity had two-fold increased risk of premature mortality compared to those without physical morbidity. Physical multimorbidity confers incremental impact on excess mortality. Early detection and intervention of physical morbidity in the initial phase of schizophrenia is necessary to reduce avoidable mortality.
Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, ...focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders.
This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (
= 1028), valproate (
= 3580), olanzapine (
= 797), quetiapine (
= 1975) or risperidone (
= 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy.
Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval CI: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 95% CI: 1.33-3.22) and risperidone (1.66 1.08-2.55) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 1.54-6.00) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 1.62-6.86), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk.
Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.
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