Comparison of Negative Symptom Network Structures Between Patients With Early and Chronic Schizophrenia: A Network and Exploratory Graph Analysis.

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.

Mentalizing impairments and hypermentalizing bias in individuals with first-episode schizophrenia-spectrum disorder and at-risk mental state: the differential roles of neurocognition and social anxiety.

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.

Modeling the effects of treatment resistance and anticholinergic burden on cognitive function domains in patients with schizophrenia.

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.

Age-related differences in the impact of resilience on mental health outcomes during the COVID-19 pandemic in Hong Kong.

OBJECTIVE: This study investigated changes in mental health in Hong Kong over two years and examined the role of resilience and age in mitigating the negative effects of public health emergencies, particularly the COVID-19 pandemic. METHODS: Complete data of interest from two telephone surveys conducted in 2020 (n = 1182) and 2021 (n = 1108) were analysed. Participants self-reported depressive and anxiety symptoms using the Patient Health Questionnaire 4-item version (PHQ), psychotic-like experiences (PLEs) using three items from the Prodromal Questionnaire Brief (PQB), and resilience using the Connor-Davidson Resilience Scale 2-item version (CD-RISC-2). RESULTS: We observed an increase in the percentage of participants with high depressive and anxiety symptoms and PLEs from 1.6% to 6.5% between 2020 and 2021. The likelihood of having high depressive and anxiety symptoms or PLEs depended on resilience and age, with no significant between-year differences. Resilience and age interaction effects were significant when comparing the high PHQ-high PQB group to the low PHQ-low PQB group only in 2021 but not in 2020. CONCLUSIONS: This study provides valuable insights into the impact of the COVID-19 pandemic on mental health in Hong Kong, emphasising the age-dependent nature of resilience in mitigating negative effects. Future research should explore the mechanisms by which resilience promotes mental health and well-being and identify ways to enhance resilience among older individuals during public health crises.

Development of an individualized risk calculator of treatment resistance in patients with first-episode psychosis (TRipCal) using automated machine learning: a 12-year follow-up study with clozapine prescription as a proxy indicator.

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.

Evaluation of a Low-Intensity Online Intervention (LiON) for Reducing Distress and Mental Health Symptoms in Young People.

PURPOSE: Enhancing young people's mental health is crucial given that most adult mental disorders develop before age 24 years. However, it is unclear whether low-intensity interventions delivered online can be effective. This study aimed to provide preliminary evidence on whether a low-intensity online intervention (LiON) can effectively lower young people's distress levels and mental health symptoms. METHODS: We compared the preintervention and postintervention changes in distress level and severity of depression and anxiety symptoms in 137 young people aged 15-24 years who used the LiON service with the three-month changes in a 1:1 propensity score-matched control group of community young people who did not use the service. They participated in one of the following modules for the first time: (1) sleep and relaxation, (2) stress-coping, and (3) problem-solving. RESULTS: Participants who received LiON intervention (mean age 22.88 [standard deviation 3.67] years, 65.7% female) showed significantly greater reductions in distress level (Cohen's f2: 0.079), as well as the severity of depressive symptoms (Cohen's f2: 0.056) and anxiety symptoms (Cohen's f2: 0.044) compared to the control group. DISCUSSION: The findings suggest that the LiON intervention has the potential to effectively reduce distress and mental health symptoms in young people. Future research should aim to confirm these findings through randomized controlled trials and explore the cost-effectiveness of the intervention.

Comorbidity of autism spectrum and attention deficit/hyperactivity disorder symptoms and their associations with 1-year mental health outcomes in adolescents and young adults.

Autism spectrum (ASD) and attention deficit/hyperactivity disorders (ADHD) share genetic, neurological, and behavioural features. However, related research in Asia is limited. We collected self-reported ASD and ADHD symptoms from 2186 Hong Kong adolescents and young adults aged 15-24 years, among whom, 1200 provided 1-year data on mental health-related outcomes. Comparative and network analyses were performed. Rating scale cutoff scores were used to divide participants into ASD, ADHD, comorbid, and control groups. The prevalence rates of ASD, ADHD, and comorbidities in Hong Kong were 13.3 %, 10.6 %, and 2.7 %, respectively. Compared with the control group, the comorbid group experienced more psychotic-like experiences (PLEs), the ASD group had poorer functioning, and the ADHD group had higher depression and anxiety symptoms and a lower quality of life after 1 year. The ability to switch attention, preference for routines and difficulty with change, and problems with organisation and planning were positively associated with depressive symptoms, forgetfulness and working memory issues with anxiety symptoms, and heightened sensory input and difficulties in sustaining attention and task completion with PLEs after 1 year. Our findings provide insight into support strategies to address the needs of young Asians to improving their well-being and long-term outcomes.

Age-matched versus non-age-matched comparison of clinical and functional differences between delusional disorder and schizophrenia: a systematic review.

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.

Functional and clinical outcomes of delusional disorder and schizophrenia patients after first episode psychosis: a 4-year follow-up study.

BACKGROUND: Literature has typically associated delusional disorder with a poorer prognosis relative to schizophrenia, without considering the confounding effect of age despite the differential age of onset. This study therefore aims to investigate the diagnostic stability, clinical, functional, and neurocognitive differences of Chinese first-episode psychosis age-matched patients with delusional disorder and schizophrenia at four years. METHODS: 71 delusional disorder and 71 age-matched schizophrenia patients were followed up for four years after their initial episode. Their symptoms, insight in psychosis, side effects of medication, medication compliance, functioning, and neurocognitive performance were assessed at four years. RESULTS: At four years, 65% of DD patients maintained the same diagnosis, while the rest shifted to SZ. Only those without a diagnostic shift were included in the analysis. Delusional disorder patients (n = 46) experienced greater general psychopathology and poorer insight, but better attitude towards medication than schizophrenia patients (n = 71). Social and occupational functioning, quality of life, and cognitive functioning, however, were similar in delusional disorder and schizophrenia patients. CONCLUSIONS: Results indicate that delusional disorder is less diagnostically stable than schizophrenia. Their outcomes in a Chinese population were largely similar at four years after removing the confounding age factor, implying that delusional disorder and schizophrenia may not be as distinct as previously thought.

COVID-19 exposure and psychosis: A comparison of clinical, functional, and cognitive profiles in remitted patients with psychosis.

The impact of Coronavirus Disease 2019 (COVID-19) on psychiatric care in remitted patients with first-episode psychosis (FEP) remains unknown. This study compared the demographic, clinical, functional, and cognitive profiles of patients recruited before and during the pandemic. The results showed that COVID patients were significantly older, smokers, alcohol users, experienced more stressors, with better functioning than pre-COVID patients. The former also had fewer severe negative and general psychopathological symptoms, more impaired insight, poorer medication compliance, and worse cognitive performance. Our findings highlighted a timely need to improve awareness into the illness and treatment in FEP patients experiencing pandemic related stressors.