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BACKGROUND AND HYPOTHESIS: Despite the clinical relevance of negative symptoms in schizophrenia, our understanding of negative symptoms remains limited. Although various courses and stages of schizophrenia have been identified, variations in the negative symptom networks between distinct stages of schizophrenia remain unexplored. STUDY DESIGN: We examined 405 patients with early schizophrenia (ES) and 330 patients with chronic schizophrenia (CS) using the Scale for the Assessment of Negative Symptoms. Network analysis and exploratory graph analysis were used to identify and compare the network structures and community memberships of negative symptoms between the two groups. Further, associations between communities and social functioning were evaluated. The potential influences of other symptom domains and confounding factors were also examined. STUDY RESULTS: Multidimensional differences were found in the networks of negative symptoms between ES and CS. The global connectivity strength was higher in the network of ES than in the network of CS. In ES, central symptoms were mainly related to expressive deficits, whereas in CS they were distributed across negative symptom domains. A three-community structure was suggested across stages but with different memberships and associations with social functioning. Potential confounding factors and symptom domains, including mood, positive, disorganization, and excitement symptoms, did not affect the network structures. CONCLUSION: Our findings revealed the presence of stage-specific network structures of negative symptoms in schizophrenia, with negative symptom communities having differential significance for social functioning. These findings provide implications for the future development of tailored interventions to alleviate negative symptoms and improve functionality across stages.
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Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS.
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Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15-50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44-1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07-3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61-10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted.
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Anomalías Inducidas por Medicamentos , Antidepresivos , Efectos Tardíos de la Exposición Prenatal , Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Femenino , Embarazo , Antidepresivos/efectos adversos , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Hong Kong/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Estudios de Cohortes , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Primer Trimestre del EmbarazoRESUMEN
Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated effect between disorder and mood-stabilizers. This population-based study identified women age 15-50 years who delivered first/singleton child in 2003-2018 in Hong Kong, utilizing territory-wide medical-record database of public healthcare services. Propensity-score weighted logistic-regression analyses adjusted for confounders were employed to examine risk of adverse pregnancy, delivery and neonatal outcomes associated with BD and mood-stabilizers (lithium, anticonvulsants and antipsychotics). Exploratory unadjusted-analyses were conducted to assess risk for congenital-malformations. Of 465,069 women, 302 had BD-diagnosis, including 168 redeemed ≥ 1 prescription of mood-stabilizers during pregnancy (treated-BD) and 134 gestationally-unexposed to mood-stabilizers (untreated-BD). BD was significantly-associated with increased risk of gestational-diabetes (adjusted-odds-ratio: 1.75 [95 % CI: 1.15-2.70]) and maternal somatic hospitalization ≤ 90 days post-discharge from index-delivery (2.12 [1.19-3.90]). In treatment status-stratified analyses, treated-BD women exhibited significantly-increased rate of gestational-diabetes (2.09 [1.21-3.70]) relative to controls (non-BD and gestationally-unexposed to mood-stabilizers). No significant association of BD or mood-stabilizers with other adverse outcomes was observed. Overall, our findings indicate that BD and mood-stabilizers are not associated with most adverse pregnancy, delivery and neonatal outcomes. Further research clarifying comparative safety of individual mood-stabilizing agents on pregnancy/neonatal outcomes is required.
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Anticonvulsivantes , Antipsicóticos , Trastorno Bipolar , Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Adulto , Adulto Joven , Adolescente , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Hong Kong/epidemiología , Recién Nacido , Anticonvulsivantes/efectos adversos , Resultado del Embarazo/epidemiología , Antipsicóticos/efectos adversos , Antimaníacos/efectos adversos , Persona de Mediana Edad , Estudios de Cohortes , Diabetes Gestacional/epidemiología , Diabetes Gestacional/tratamiento farmacológico , Compuestos de Litio/efectos adversosRESUMEN
Functional connectivity resting-state functional magnetic resonance imaging has been proposed to predict antipsychotic treatment response in schizophrenia. However, only a few prospective studies have examined baseline resting-state functional magnetic resonance imaging data in drug-naïve first-episode schizophrenia patients with regard to subsequent treatment response. Data-driven approaches to conceptualize and measure functional connectivity patterns vary broadly, and model-free, voxel-wise, whole-brain analysis techniques are scarce. Here, we apply such a method, called connectivity concordance mapping to resting-state functional magnetic resonance imaging data acquired from an Asian sample (n = 60) with first-episode psychosis, prior to pharmaceutical treatment. Using a longitudinal design, 12 months after the resting-state functional magnetic resonance imaging, we measured and classified patients into two groups based on psychometric testing: treatment responsive and treatment resistant. Next, we compared the two groups' connectivity concordance maps that were derived from the resting-state functional magnetic resonance imaging data at baseline. We have identified consistently higher functional connectivity in the treatment-resistant group in a network including the left hippocampus, bilateral insula and temporal poles. These data-driven novel findings can help researchers to consider new regions of interest and facilitate biomarker development in order to identify treatment-resistant schizophrenia patients early, in advance of treatment and at the time of their first psychotic episode.
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AIMS: 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. METHODS: This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 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. RESULTS: 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. CONCLUSION: 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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Antimaníacos , Antipsicóticos , Trastorno Bipolar , Puntaje de Propensión , Fumarato de Quetiapina , Ácido Valproico , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/mortalidad , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Ácido Valproico/uso terapéutico , Antimaníacos/uso terapéutico , Estudios de Cohortes , Fumarato de Quetiapina/uso terapéutico , Fumarato de Quetiapina/efectos adversos , Olanzapina/uso terapéutico , Hong Kong/epidemiología , Risperidona/uso terapéutico , Risperidona/efectos adversos , Litio/uso terapéutico , Causas de MuerteRESUMEN
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Ansiedad , COVID-19 , Depresión , Trastornos por Estrés Postraumático , Humanos , COVID-19/psicología , COVID-19/epidemiología , Femenino , Masculino , Estudios Transversales , Hong Kong/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Depresión/epidemiología , Depresión/psicología , Ansiedad/psicología , Ansiedad/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Adaptación Psicológica , SARS-CoV-2 , Resiliencia Psicológica , Distrés Psicológico , Pueblos del Este de AsiaRESUMEN
The contribution of anticholinergic burden to cognitive function in patients with treatment resistant schizophrenia (TRS) is uncertain. This case-control study aims to comprehensively examine the association between treatment resistance and cognitive functions and the contribution of anticholinergic burden in patients with schizophrenia. Anticholinergic burden of all patients was calculated using the Anticholinergic Cognitive Burden scale. Exploratory Factor Analysis of 11 cognitive assessments identified four cognitive domains: verbal memory, attention and general cognitive functions, visual memory and processing speed, and executive function. Two structural equation models (SEM) examined the relationship of TRS and these cognitive functions with, and without considering anticholinergic burden. A total of 288 participants were included (TRS N=111, non-TRS N=177). Patients with TRS performed poorer than the non-TRS group only in the executive function domain. Anticholinergic burden contributed significantly to the attention and general cognitive functions, visual memory and processing speed, and executive function. The impact of TRS on executive function was no longer significant after adding anticholinergic burden to the SEM. Results suggested that anticholinergic burden contributes to a wide range of cognitive function impairment in patients with schizophrenia and is likely to be part of the apparent differences of cognitive function between TRS and non-TRS.
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Antagonistas Colinérgicos , Disfunción Cognitiva , Función Ejecutiva , Humanos , Antagonistas Colinérgicos/efectos adversos , Masculino , Femenino , Adulto , Función Ejecutiva/efectos de los fármacos , Función Ejecutiva/fisiología , Estudios de Casos y Controles , Persona de Mediana Edad , Disfunción Cognitiva/inducido químicamente , Esquizofrenia Resistente al Tratamiento/tratamiento farmacológico , Atención/efectos de los fármacos , Cognición/efectos de los fármacos , Antipsicóticos/efectos adversos , Antipsicóticos/farmacología , Esquizofrenia/tratamiento farmacológico , Pruebas Neuropsicológicas , Psicología del Esquizofrénico , Memoria/efectos de los fármacosAsunto(s)
Ansiedad , COVID-19 , Depresión , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , COVID-19/psicología , COVID-19/complicaciones , Depresión/psicología , Femenino , Masculino , Ansiedad/psicología , Adulto , Análisis de Mediación , Persona de Mediana Edad , Rumiación Cognitiva/fisiologíaRESUMEN
Background: The UN warns that Myanmar faces the 'triple crises' of mass conflict, uncontrolled COVID-19, and economic collapse. Therefore, we aimed to assess the population mental health burden, healthcare needs, and the associated risk factors in Myanmar. Methods: We established a nationwide random sample and recruited 1038 adults via random digit dialling from July 3-Aug 9, 2021, during the ongoing conflict since Feb 1, 2021, and surge in SARS-CoV-2 infections. Probable post-traumatic stress disorder (PTSD) was assessed using the PTSD Checklist-Civilian Version. Probable depression and anxiety were assessed using the Patient Health Questionnaire-2 and the Generalized Anxiety Disorder-2. We calculated population attributable fractions for probable mental disorders using multivariable logistic regression models. Based on the mental health burden and healthcare-seeking patterns, we projected the need for mental health services. Findings: During the 'triple crises', a third of adults in Myanmar (34.9%, 95% CI 32.0-37.7) reported a probable mental disorder. Prevalence of probable PTSD, depression, and anxiety were 8.1% (6.6-9.7), 14.3% (12.0-16.6), and 22.2% (19.7-24.7), respectively. We estimated that up to 79.9% (43.8-97.9) of probable PTSD was attributable to political stress. This corresponds to 2.1 million (1.1-3.2 million) fewer adults with probable PTSD if political stress was removed from the population. The mental health burden could translate into roughly 5.9 million adults seeking mental health services. Interpretation: The mental health burden in Myanmar is substantial, and population mental health might only be restored when the three crises have ended. An accelerated peace process is critical to protecting Myanmar's population mental health. Funding: This research was supported the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU 17606122) and the Michele Tansella Award.
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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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COVID-19 , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos por Estrés Postraumático , Humanos , Femenino , Masculino , Calidad de Vida , Hong Kong/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Pacientes Ambulatorios , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
AIMS: Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic. METHODS: By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions. RESULTS: A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021. CONCLUSIONS: Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
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COVID-19 , Humanos , COVID-19/epidemiología , Incidencia , Salud Mental , Pandemias , Trastornos de AnsiedadRESUMEN
Introduction: Previous coronavirus, 2019 (COVID-19) research has applied network analysis to examine relationships between psychopathological symptoms but rarely extended to potential risk and protective factors or the influence of COVID-19 infection history. This study examined complex inter-relationships between psychopathological symptoms, COVID-19-related stressors, perceived social support, and COVID-19 infection history among Chinese university/college students during the peak of fifth pandemic wave using a network analysis approach. Methods: A Least Absolute Shrinkage and Selection Operator-regularized partial correlation network using Gaussian graphical model was constructed in 1,395 Chinese university/college students in Hong Kong who completed a survey between 15 March and 3 April, 2022. Depressive, anxiety, and acute/traumatic stress symptoms were measured by Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Impact of Event Scale-6, respectively. COVID-19-related stressors and perceived social support were measured. Network differences by COVID-19 infection history (COVID-network vs. no_COVID-network) and network communities were examined. Results: Our results showed that the most influential nodes were depressed mood, uncontrollable worries, and uncontrollable thoughts about COVID-19. The main bridging symptoms were concentration problems and psychomotor problems. The COVID-network, comprising participants with a history of COVID-19 infection only, was significantly stronger than the no_COVID-network. Perceived social support and stress from conflicts with family/friends formed a unique community with negative cognition and suicidal idea in the COVID-network only. Conclusion: Our findings indicate that specific interventions targeting interpersonal conflicts and concentration problems as well as facilitating stress buffering effects of social support may represent effective strategies to reduce psychological distress in university/college students during COVID-19 and should be considered for future pandemic preparedness.
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About 15-40% of patients with schizophrenia are treatment resistance (TR) and require clozapine. Identifying individuals who have higher risk of development of TR early in the course of illness is important to provide personalized intervention. A total of 1400 patients with FEP enrolled in the early intervention for psychosis service or receiving the standard psychiatric service between July 1, 1998, and June 30, 2003, for the first time were included. Clozapine prescriptions until June 2015, as a proxy of TR, were obtained. Premorbid information, baseline characteristics, and monthly clinical information were retrieved systematically from the electronic clinical management system (CMS). Training and testing samples were established with random subsampling. An automated machine learning (autoML) approach was used to optimize the ML algorithm and hyperparameters selection to establish four probabilistic classification models (baseline, 12-month, 24-month, and 36-month information) of TR development. This study found 191 FEP patients (13.7%) who had ever been prescribed clozapine over the follow-up periods. The ML pipelines identified with autoML had an area under the receiver operating characteristic curve ranging from 0.676 (baseline information) to 0.774 (36-month information) in predicting future TR. Features of baseline information, including schizophrenia diagnosis and age of onset, and longitudinal clinical information including symptoms variability, relapse, and use of antipsychotics and anticholinergic medications were important predictors and were included in the risk calculator. The risk calculator for future TR development in FEP patients (TRipCal) developed in this study could support the continuous development of data-driven clinical tools to assist personalized interventions to prevent or postpone TR development in the early course of illness and reduce delay in clozapine initiation.
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Clozapina , Trastornos Psicóticos , Humanos , Clozapina/efectos adversos , Estudios de Seguimiento , Trastornos Psicóticos/tratamiento farmacológico , Aprendizaje Automático , PrescripcionesRESUMEN
Sources of heterogeneity in risk of stroke and mortality risk following acute-stroke in schizophrenia are understudied. We systematically searched four electronic-databases until 1-November-2022, and conducted meta-analysis to synthesize estimates of stroke-risk and post-stroke mortality for schizophrenia patients relative to non-schizophrenia counterparts. Subgroup-analyses and meta-regression models stratified by sex, nature of sample (incident/prevalent), geographical region, study-period and time-frame following stroke were conducted when applicable. Fifteen and 5 studies were included for meta-analysis of stroke-risk (n=18,368,253; 129,095 schizophrenia patients) and all-cause post-stroke mortality (n=289,231; 4,477 schizophrenia patients), respectively. Schizophrenia patients exhibited elevated stroke-risk (relative-risk =1.55[95% CI:1.31-1.84]) relative to non-schizophrenia controls. Schizophrenia was associated with increased stroke-risk in both sexes, study-periods of 1990s and 2000s, and irrespective of nature of sample and geographical regions. Meta-regression revealed regional differences in relative-risk for stroke, but limited by small number of studies. After removal of an outlier study, meta-analysis demonstrated that schizophrenia was associated with increased overall (hazard-ratio=1.37[1.30-1.44]), short-term (≤90 days; 1.29[1.14-1.46]) and longer-term (≥1 year; 1.45[1.32-1.60]) post-stroke mortality rates. Raised post-stroke mortality rate for schizophrenia was observed irrespective of nature of sample, geographical regions and study-periods. Taken together, schizophrenia is associated with increased stroke-risk and post-stroke mortality. Multilevel-interventions are required to reduce these physical-health disparities.
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Esquizofrenia , Accidente Cerebrovascular , Masculino , Femenino , Humanos , Esquizofrenia/complicaciones , Accidente Cerebrovascular/complicacionesRESUMEN
Background: Mental disorders are associated with premature mortality. There is increasing research examining life expectancy and years-of-potential-life-lost (YPLL) to quantify the disease impact on survival in people with mental disorders. We aimed to systematically synthesize studies to estimate life expectancy and YPLL in people with any and specific mental disorders across a broad spectrum of diagnoses. Methods: In this systematic review and meta-analysis, we searched Embase, MEDLINE, PsychINFO, WOS from inception to July 31, 2023, for published studies reporting life expectancy and/or YPLL for mental disorders. Criteria for study inclusion were: patients of all ages with any mental disorders; reported data on life expectancy and/or YPLL of a mental-disorder cohort relative to the general population or a comparison group without mental disorders; and cohort studies. We excluded non-cohort studies, publications containing non-peer-reviewed data or those restricted to population subgroups. Survival estimates, i.e., life expectancy and YPLL, were pooled (based on summary data extracted from the included studies) using random-effects models. Subgroup analyses and random-effects meta-regression analyses were performed to explore sources of heterogeneity. Risk-of-bias assessment was evaluated using the Newcastle-Ottawa Scale. This study is registered with PROSPERO (CRD42022321190). Findings: Of 35,865 studies identified in our research, 109 studies from 24 countries or regions including 12,171,909 patients with mental disorders were eligible for analysis (54 for life expectancy and 109 for YPLL). Pooled life expectancy for mental disorders was 63.85 years (95% CI 62.63-65.06; I2 = 100.0%), and pooled YPLL was 14.66 years (95% CI 13.88-15.98; I2 = 100.0%). Disorder-stratified analyses revealed that substance-use disorders had the shortest life expectancy (57.07 years [95% CI 54.47-59.67]), while neurotic disorders had the longest lifespan (69.51 years [95% CI 67.26-71.76]). Substance-use disorders exhibited the greatest YPLL (20.38 years [95% CI 18.65-22.11]), followed by eating disorders (16.64 years [95% CI 7.45-25.82]), schizophrenia-spectrum disorders (15.37 years [95% CI 14.18-16.55]), and personality disorders (15.35 years [95% CI 12.80-17.89]). YPLLs attributable to natural and unnatural deaths in mental disorders were 4.38 years (95% CI 3.15-5.61) and 8.11 years (95% CI 6.10-10.13; suicide: 8.31 years [95% CI 6.43-10.19]), respectively. Stratified analyses by study period suggested that the longevity gap persisted over time. Significant cross-study heterogeneity was observed. Interpretation: Mental disorders are associated with substantially reduced life expectancy, which is transdiagnostic in nature, encompassing a wide range of diagnoses. Implementation of comprehensive and multilevel intervention approaches is urgently needed to rectify lifespan inequalities for people with mental disorders. Funding: None.
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Background: It has been widely suggested that delusional disorder (DD) differs from schizophrenia (SZ). However, whether the two disorders are truly distinct from each other is inconclusive as an older age of onset is closely linked to a better prognosis in psychotic disorders. In order to delineate the potential influence of age on outcomes, we undertook a systematic review on the clinical and functional differences between DD and SZ in age-matched and non-age-matched cohorts. Methods: Electronic databases were retrieved up to May 2022. Included studies were analyzed with reference to statements about clinical, cognitive and functional differences between DD and SZ. Results: Data synthesized from 8 studies showed (1) extensive effects of age on positive, general psychopathological symptoms and functioning, but (2) consistent differences between the two disorders in terms of negative symptoms and hospitalizations regardless of age matching. Conclusion: There is currently insufficient evidence to conclude whether DD is completely distinct from SZ, but our review showed support for the confounding effect of age in comparisons of psychotic disorders with different ages of onset. Future studies shall take note of other possible confounding variables, methods of age-matching and the importance of longitudinal information in deducing whether the two disorders differ from each other in course and outcome.
RESUMEN
Impairments in effort-cost decision-making have been consistently observed in people with schizophrenia (SZ) and may be an important mechanism of negative symptoms. However, the processes that give rise to impairments in effort-cost decision-making are unclear, leading to limited progress in identifying the most relevant treatment targets. Drawing from cognitive models of negative symptoms and goal-directed behavior, this study aimed to examine how and under what type of task conditions defeatist performance beliefs contribute to these decision-making processes. Outpatients with SZ (n = 30) and healthy controls (CN; n = 28) completed a cognitive effort allocation task, the Cognitive Effort-Discounting (COGED) task, which assesses participants' willingness to exert cognitive effort for monetary rewards based on parametrically varied working memory demands (completing N-back levels). Results showed that although participants with SZ demonstrated reduced willingness to work for rewards across N-back levels compared to CN participants, they showed less choice modulation across different N-back conditions. However, among SZ participants with greater defeatist performance beliefs, there was a reduced willingness to choose the high effort option at higher N-back levels (N-back levels 3, 4, and 5 versus 2-back). Results suggest that compared to CN, the SZ group's subjective willingness to expend effort largely did not dynamically adjust as cognitive load increased. However, defeatist beliefs may undermine willingness to expend cognitive effort, especially when cognitive task demands are high. These beliefs may be a viable treatment target to improve effort-cost decision-making impairments in people with SZ.