Whole-exome sequencing in a Chinese sample provides preliminary evidence for the link between rare/low-frequency immune-related variants and early-onset schizophrenia.

Rare and low-frequency variants contribute to schizophrenia (SCZ), and may influence its age-at-onset (AAO). We examined the association of rare or low-frequency deleterious coding variants in Chinese patients with SCZ. We collected DNA samples in 197 patients with SCZ spectrum disorder and 82 healthy controls (HC), and performed exome sequencing. The AAO variable was ascertained in the majority of SCZ participants for identify the early-onset (EOS, AAO<=18) and adult-onset (AOS, AAO>18) subgroups. We examined the overall association of rare/low-frequency, damaging variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels using Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was conducted. Resampling was used to obtain empirical p-values and to control for family-wise error rate (FWER). In binary-trait association tests, we identified 5 potential candidate risk genes and 10 gene ontology biological processes (GOBP) terms, among which PADI2 reached FWER-adjusted significance. In quantitative rare-variant association tests, we found marginally significant correlations of AAO with alterations in 4 candidate risk genes, and 5 GOBP pathways. Together, the biological and functional profiles of these genes and gene sets supported the involvement of perturbations of neural systems in SCZ, and altered immune functions in EOS.

Early-onset schizophrenia is associated with immune-related rare variants in a Chinese sample.

Background: Rare variants are likely to contribute to schizophrenia (SCZ), given the large discrepancy between the heritability estimated from twin and GWAS studies. Furthermore, the nature of the rare-variant contribution to SCZ may vary with the "age-at-onset" (AAO), since early-onset has been suggested as being indicative of neurodevelopment deviance. Objective: To examine the association of rare deleterious coding variants in early- and adult-onset SCZ in a Chinese sample. Method: Exome sequencing was performed on DNA from 197 patients with SCZ spectrum disorder and 82 healthy controls (HC) of Chinese ancestry recruited in Hong Kong. We also gathered AAO information in the majority of SCZ samples. Patients were classified into early-onset (EOS, AAO<18) and adult-onset (AOS, AAO>18). We collapsed the rare variants to improve statistical power and examined the overall association of rare variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels by Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was also conducted. We focused on variants which were predicted to have a medium or high impact on the protein-encoding process as defined by Ensembl. We applied a 100000-time permutation test to obtain empirical p-values, with significance threshold set at p < 1e -3 to control family-wise error rates. Moreover, we compared the burden of targeted rare variants in significant risk genes and gene sets in cases and controls. Results: Based on several binary-trait association tests (i.e., SCZ vs HC, EOS vs HC and AOS vs HC), we identified 7 candidate risk genes and 20 gene ontology biological processes (GOBP) terms, which exhibited higher burdens in SCZ than in controls. Based on quantitative rare-variant association tests, we found that alterations in 5 candidate risk genes and 7 GOBP pathways were significantly correlated with AAO. Based on biological and functional profiles of the candidate risk genes and gene sets, our findings suggested that, in addition to the involvement of perturbations in neural systems in SCZ in general, altered immune responses may be specifically implicated in EOS. Conclusion: Disrupted immune responses may exacerbate abnormal perturbations during neurodevelopment and trigger the early onset of SCZ. We provided evidence of rare variants increasing SCZ risk in the Chinese population.

Pathway-Specific Polygenic Scores Improve Cross-Ancestry Prediction of Psychosis and Clinical Outcomes.

Psychotic disorders are debilitating conditions with disproportionately high public health burden. Genetic studies indicate high heritability, but current polygenic scores (PGS) account for only a fraction of variance in psychosis risk. PGS often show poor portability across ancestries, performing significantly worse in non-European populations. Pathway-specific PGS (pPGS), which restrict PGS to genomic locations within distinct biological units, could lead to increased mechanistic understanding of pathways that lead to risk and improve cross-ancestry prediction by reducing noise in genetic predictors. This study examined the predictive power of genome-wide PGS and nine pathway-specific pPGS in a unique Chinese-ancestry sample of deeply-phenotyped psychosis patients and non-psychiatric controls. We found strong evidence for the involvement of schizophrenia-associated risk variants within "nervous system development" (p=2.5e-4) and "regulation of neuron differentiation" pathways (p=3.0e-4) in predicting risk for psychosis. We also found the "ion channel complex" pPGS, with weights derived from GWAS of bipolar disorder, to be strongly associated with the number of inpatient psychiatry admissions a patient experiences (p=1.5e-3) and account for a majority of the signal in the overall bipolar PGS. Importantly, although the schizophrenia genome-wide PGS alone explained only 3.7% of the variance in liability to psychosis in this Chinese ancestry sample, the addition of the schizophrenia-weighted pPGS for "nervous system development" and "regulation of neuron differentiation" increased the variance explained to 6.9%, which is on-par with the predictive power of PGS in European ancestry samples. Thus, not only can pPGS provide greater insight into mechanisms underlying genetic risk for disease and clinical outcomes, but may also improve cross-ancestry risk prediction accuracy.

Emotion-behaviour decoupling and experiential pleasure deficits predict negative symptoms and functional outcome in first-episode schizophrenia patients.

BACKGROUND: Emotion-behaviour decoupling refers to the failure to translate emotion into motivated behaviour, and is a putative marker for schizophrenia. The heterogeneity of experiential pleasure and emotion expressivity deficits has been reported in schizophrenia patients. These three constructs are believed to contribute to negative symptoms, but very few studies have examined their predictive ability for clinical and functional outcome of schizophrenia. This study aimed to clarify whether these three constructs influence clinical and functional outcome of schizophrenia. METHOD: At baseline, 127 first-episode schizophrenia patients completed a behavioural paradigm for emotion-behaviour decoupling, and self-report scales for experiential pleasure and emotion expressivity deficits. Cluster-analysis was applied to characterize schizophrenia subgroups based on these three constructs. At end-point (mean follow-up = 5.37 years, SD = 1.03 years), 85 schizophrenia patients were reassessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and a clinician-rated social functioning scale. RESULTS: Cluster 1 (n = 74) did not show emotion-behaviour decoupling, and had intact experiential pleasure and emotion expressivity. Cluster 2 (n = 29) showed emotion-behaviour decoupling and experiential pleasure deficits. Cluster 3 (n = 24) showed emotion expressivity deficits. At endpoint, the three clusters differed significantly in CAINS MAP factor (p = 0.016) and social functioning (p = 0.019), but not CAINS EXP factor. Specifically, Cluster 2 (n = 18) showed more severe negative symptoms of CAINS MAP factor (p = 0.046) and poorer social functioning (p = 0.022) than Cluster 1 (n = 49). Cluster 3 (n = 18) did not differ from Cluster 1 and Cluster 2 in negative symptoms and social functioning. DISCUSSION: Emotion-behaviour decoupling and experiential pleasure deficits predicted clinical and functional outcome of schizophrenia.

The Effects of a Mindfulness-Based Family Psychoeducation Intervention for the Caregivers of Young Adults with First-Episode Psychosis: A Randomized Controlled Trial.

OBJECTIVE: In this study, we investigated the effects of a mindfulness-based family psychoeducation (MBFPE) program on the mental-health outcomes of both caregivers and young adults with first-episode psychosis with an onset in the past three years through a multi-site randomized controlled trial. We also studied the outcomes of three potential mediating effects of interpersonal mindfulness, expressed emotions, and non-attachment on the program. METHOD: We randomly assigned 65 caregivers of young adults with psychosis to MBFPE (n = 33) or an ordinary family psychoeducation (FPE) program (n = 32); among them, 18 young adults in recovery also participated in the evaluation of outcomes. RESULTS: Intent-to-treat analyses were conducted. No significant time × group interaction effects of MBFPE and FPE programs were found in any of the caregivers' outcomes. However, the young adults with psychosis reported higher levels of recovery after the MBFPE program than after the ordinary FPE program (F = 8.268, p = 0.012, d = 1.484). They also reported a larger reduction in over-involvement of their caregivers (F = 4.846, p = 0.044, d = 1.136), showing that MBFPE had a superior effect to FPE in promoting recovery and reducing over-involvement. CONCLUSIONS: A brief psychoeducation program may not reduce the burden on or improve the mental-health outcome of caregivers of individuals with recent-onset psychosis. However, integrating mindfulness into a conventional family psychoeducation program may reduce the expressed emotions of caregivers, especially over-involvement. Further studies should explore how psychoeducation programs can reduce the impact of psychosis on family through sustainable effects in terms of reducing their burden and expressed emotions, using a rigorous study and adequate sample size.

Bridge centrality network structure of negative symptoms in people with schizophrenia.

Negative symptoms are complex psychopathology. Although evidence generally supported the NIMH five consensus domains, research seldom examined measurement invariance of this model, and domain-specific correspondence across multiple scales. This study aimed to examine the interrelationship between negative symptom domains captured by different rating scales, and to examine the domain-specific correspondence across multiple scales. We administered the Brief Negative Symptom Scale (BNSS), the Self-evaluation of Negative Symptoms (SNS), and the Scale for Assessment of Negative Symptoms (SANS) to 204 individuals with schizophrenia. We used network analysis to examine the interrelationship between negative symptom domains. Besides regularized partial correlation network, we estimated bridge centrality indices to investigate domain-specific correspondence, while taking each scale as an independent community. The regularized partial correlation network showed that the SNS nodes clustered together, whereas the SANS and the BNSS nodes intermingled together. The SANS attention domain lied at the periphery of the network according to the Fruchterman-Reingold algorithm. The SANS anhedonia-asociality (strength = 1.48; EI = 1.48) and the SANS affective flattening (strength = 1.06; EI = 1.06) had the highest node strength and EI. Moreover, the five nodes of the BNSS bridged the nodes of the SANS and the SNS. BNSS blunted affect (strength = 0.76; EI = 0.76) and SANS anhedonia-asociality (strength = 0.76; EI = 0.74) showed the highest bridge strength and bridge EI. The BNSS captures negative symptoms and bridges the symptom domains measured by the SANS and the SNS. The three scales showed domain-specific correspondence.

Audiovisual temporal processing in adult patients with first-episode schizophrenia and high-functioning autism.

Schizophrenia and autism spectrum disorder (ASD) are both neurodevelopmental disorders with altered sensory processing. Widened temporal binding window (TBW) signifies reduced sensitivity to detect stimulus asynchrony, and may be a shared feature in schizophrenia and ASD. Few studies directly compared audiovisual temporal processing ability in the two disorders. We recruited 43 adult patients with first-episode schizophrenia (FES), 35 average intelligent and verbally-fluent adult patients with high-functioning ASD and 48 controls. We employed two unisensory Temporal Order Judgement (TOJ) tasks within visual or auditory modalities, and two audiovisual Simultaneity Judgement (SJ) tasks with flash-beeps and videos of syllable utterance as stimuli. Participants with FES exhibited widened TBW affecting both speech and non-speech processing, which were not attributable to altered unisensory sensory acuity because they had normal visual and auditory TOJ thresholds. However, adults with ASD exhibited intact unisensory and audiovisual temporal processing. Lower non-verbal IQ was correlated with larger TBW width across the three groups. Taking our findings with earlier evidence in chronic samples, widened TBW is associated with schizophrenia regardless illness stage. The altered audiovisual temporal processing in ASD may ameliorate after reaching adulthood.

The Important Role of Motivation and Pleasure Deficits on Social Functioning in Patients With Schizophrenia: A Network Analysis.

Negative symptoms, particularly the motivation and pleasure (MAP) deficits, are associated with impaired social functioning in patients with schizophrenia (SCZ). However, previous studies seldom examined the role of the MAP on social functioning while accounting for the complex interplay between other psychopathology. This network analysis study examined the network structure and interrelationship between negative symptoms (at the "symptom-dimension" and "symptom-item" levels), other psychopathology and social functioning in a sample of 269 patients with SCZ. The psychopathological symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Positive and Negative Syndrome Scale (PANSS). Social functioning was evaluated using the Social and Occupational Functioning Assessment Scale (SOFAS). Centrality indices and relative importance of each node were estimated. The network structures between male and female participants were compared. Our resultant networks at both the "symptom-dimension" and the "symptom-item" levels suggested that the MAP factor/its individual items were closely related to social functioning in SCZ patients, after controlling for the complex interplay between other nodes. Relative importance analysis showed that MAP factor accounted for the largest proportion of variance of social functioning. This study is among the few which used network analysis and the CAINS to examine the interrelationship between negative symptoms and social functioning. Our findings supported the pivotal role of the MAP factor to determine SCZ patients' social functioning, and as a potential intervention target for improving functional outcomes of SCZ.

Structural network alterations and their association with neurological soft signs in schizophrenia: Evidence from clinical patients and unaffected siblings.

BACKGROUND: Grey matter abnormalities and neurological soft signs (NSS) have been found in schizophrenia patients and their unaffected relatives. Evidence suggested that NSS are associated with grey matter morphometrical alterations in multiple regions in schizophrenia. However, the association between NSS and structural abnormalities at network level remains largely unexplored, especially in the schizophrenia and unaffected siblings. METHOD: We used source-based morphometry (SBM) to examine the association of structural brain network characteristics with NSS in 62 schizophrenia patients, 25 unaffected siblings, and 60 healthy controls. RESULTS: Two components, namely the IC-5 (superior temporal gyrus, inferior frontal gyrus and insula network) and the IC-10 (parahippocampal gyrus, fusiform, thalamus and insula network) showed significant grey matter reductions in schizophrenia patients compared to healthy controls and unaffected siblings. Further association analysis demonstrated separate NSS-related grey matter covarying patterns in schizophrenia, unaffected siblings and healthy controls. Specifically, NSS were negatively associated with IC-1 (hippocampus, caudate and thalamus network) and IC-5 in schizophrenia, but with IC-3 (caudate, superior and middle frontal cortices network) in unaffected siblings and with IC-5 in healthy controls. CONCLUSION: Our results confirmed the key cortical and subcortical network abnormalities and NSS-related grey matter covarying patterns in the schizophrenia and unaffected siblings. Our findings suggest that brain regions implicating genetic liability to schizophrenia are partly separated from brain regions implicating neural abnormalities.

Different trajectories of neurological soft signs progression between treatment-responsive and treatment-resistant schizophrenia patients.

Schizophrenia patients exhibit subtle and non-localizing neurological abnormalities, known as neurological soft signs (NSS). Life-span evidence suggests that NSS vary along the course of schizophrenia. An association between NSS and treatment response has been proposed, suggesting that NSS reflect the underlying neuropathology development in schizophrenia. However, few studies have investigated the relationship between NSS and treatment resistance in first-episode schizophrenia patients. We conducted a longitudinal study on 52 first-episode schizophrenia patients, who were assessed at baseline, the sixth month, and the fifth year using the abridged version of the Cambridge Neurological Inventory. The trajectories of NSS between 29 treatment-responsive patients (with full symptomatic remission) and 23 treatment-resistant patients (who received clozapine) were compared using mixed model ANOVA. We also controlled for the effect of age and estimated IQ, using a mixed ANCOVA model. Although the two schizophrenia groups had comparable NSS at the baseline, their trajectories of NSS differed significantly. Compared with their treatment-responsive counterparts, treatment-resistant schizophrenia patients had worsening of NSS over time. Our findings support the potential utility of NSS in identifying treatment resistance in first-episode schizophrenia. Progressive worsening of NSS in treatment-resistant schizophrenia patients may reflect the development of underlying neuropathology. Further studies using large samples of treatment-resistant schizophrenia patients are needed.

Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia.

Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.

Cerebellar hypoactivation is associated with impaired sensory integration in schizophrenia.

To clarify the involvement of the cerebellum in impaired sensory integration in patients with schizophrenia, 52 first-episode patients with schizophrenia and 52 age- and sex-matched healthy controls underwent a verified sensory integration imaging task to examine the whole-brain dysfunction underlying impaired sensory integration. The familiality of cerebellar activation when integrating sensory stimuli was investigated in 25 siblings of the patients with schizophrenia, while the heritability of cerebellar activation was estimated in 56 monozygotic twins and 56 dizygotic twins. In addition, the functional connectivity between the cerebellum and the remaining regions of the whole brain was explored with psychophysiological interaction analysis. Relative to healthy controls, patients with schizophrenia showed reduced cerebellar activation when performing the sensory integration task in the whole-brain analysis. This reduced cerebellar activation was also found in the siblings of patients with schizophrenia, but to a lesser extent compared with schizophrenia patients. Cerebellar activation during sensory integration was also found to be significantly heritable. Furthermore, dysconnectivity within the cerebellum was found in patients with schizophrenia when integrating auditory and visual stimuli. These findings highlight the role of cerebellar dysfunction in the pathophysiology of schizophrenia symptoms and its potential role as an endophenotype of schizophrenia spectrum disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Tractography-based classification in distinguishing patients with first-episode schizophrenia from healthy individuals.

BACKGROUND: Schizophrenia has been characterized as a neurodevelopmental disorder of brain disconnectivity. However, whether disrupted integrity of white matter tracts in schizophrenia can potentially serve as individual discriminative biomarkers remains unclear. METHODS: A random forest algorithm was applied to tractography-based diffusion properties obtained from a cohort of 65 patients with first-episode schizophrenia (FES) and 60 healthy individuals to investigate the machine-learning discriminative power of white matter disconnectivity. Recursive feature elimination was used to select the ultimate white matter features in the classification. Relationships between algorithm-predicted probabilities and clinical characteristics were also examined in the FES group. RESULTS: The classifier was trained by 80% of the sample. Patients were distinguished from healthy individuals with an overall accuracy of 71.0% (95% confident interval: 61.1%, 79.6%), a sensitivity of 67.3%, a specificity of 75.0%, and the area under receiver operating characteristic curve (AUC) was 79.3% (χ2 p < 0.001). In validation using the held-up 20% of the sample, patients were distinguished from healthy individuals with an overall accuracy of 76.0% (95% confident interval: 54.9%, 90.6%), a sensitivity of 76.9%, a specificity of 75.0%, and an AUC of 73.1% (χ2 p = 0.012). Diffusion properties of inter-hemispheric fibres, the cerebello-thalamo-cortical circuits and the long association fibres were identified to be the most discriminative in the classification. Higher predicted probability scores were found in younger patients. CONCLUSIONS: Our findings suggest that the widespread connectivity disruption observed in FES patients, especially in younger patients, might be considered potential individual discriminating biomarkers.

Clustering of Schizotypal Features in Unaffected First-Degree Relatives of Schizophrenia Patients.

Meehl conceptualized schizotypy as the phenotypic manifestations of a neural integrative defect resulting from a schizophrenia diathesis. The majority of schizotypy studies recruited subjects from the general population and revealed a multidimensional construct. This 2-phase investigation first examined the clustering of schizotypy in 194 unaffected relatives of schizophrenia patients using the Chapman Psychosis Proneness scales and then directly compared the cognitive profiles of negative schizotypal individuals and positive schizotypal individuals with schizophrenia patients and controls. In the first phase, cluster analysis categorized 194 unaffected relatives of schizophrenia patients into positive schizotypy (n = 33), negative schizotypy (n = 66), mixed schizotypy (n = 27), and low schizotypy (n = 64). Positive schizotypal participants showed more self-report pleasure experiences than negative schizotypal participants, replicating earlier cluster analytic findings. In the second phase, 27 negative schizotypal individuals, 18 positive schizotypal individuals, 19 schizophrenia patients, and 29 controls were recruited. Although the groups were matched in terms of age, gender, and IQ, they differed significantly in cognitive profiles. While schizophrenia patients exhibited the broadest cognitive impairments, negative schizotypal participants exhibited visual memory, working memory, and verbal fluency impairments, and positive schizotypal participants exhibited logical memory, visual memory, working memory, and theory-of-mind impairments. Among people with familial risk of schizophrenia, individuals exhibiting positive rather than negative schizotypal features resembled schizophrenia patients in cognitive profiles. Using the psychometric-familial method to identify schizotypy, our findings support the heterogeneity of schizotypy as well as the potential utility of the positive schizotypy dimension in genetically high-risk individuals to predict the risk of developing schizophrenia.

Cross Cultural Validation and Extension of the Clinical Assessment Interview for Negative Symptoms (CAINS) in the Chinese Context: Evidence from a Spectrum Perspective.

The Clinical Assessment Interview for Negative Symptoms (CAINS) was designed in accordance with the recent theory and research in social affective neuroscience and to address the psychometric and conceptual limitations of other instruments assessing negative symptoms. The present study aimed to provide a large-scale validation of the CAINS in China and examine its applicability and validity evidence across the schizophrenia spectrum. Using confirmatory factor analysis, our results replicated the original findings in the US development samples that the CAINS possesses a stable 2-factor structure, namely "motivation/pleasure" and "expression". We also found significant correlations between the CAINS and other negative symptom measures. The CAINS demonstrated good discriminant validity in differentiating negative symptoms in people with schizophrenia, nonpsychotic first-degree relatives and people with social anhedonia. People with schizophrenia exhibited significantly higher CAINS subscale scores than first-degree relatives and healthy controls. In addition, first-degree relatives had higher "motivation/pleasure" scores than healthy controls. The "motivation/pleasure" subscale scores of individuals with social anhedonia were also significantly higher than healthy controls.

In vivo gamma-aminobutyric acid and glutamate levels in people with first-episode schizophrenia: A proton magnetic resonance spectroscopy study.

BACKGROUND: Gamma-aminobutyric acid (GABA) dysfunction and its consequent imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA production would lead to a disinhibition of glutamatergic neurons and subsequently cause a disruption of the modulation between GABAergic interneurons and glutamatergic neurons. In this study, levels of GABA, Glx (summation of glutamate and glutamine), and other metabolites in the anterior cingulate cortex were measured and compared between first-episode schizophrenia subjects and healthy controls (HC). Diagnostic potential of GABA and Glx as upstream biomarkers for schizophrenia was explored. METHODS: Nineteen first-episode schizophrenia subjects and fourteen HC participated in this study. Severity of clinical symptoms of patients was measured with Positive and Negative Syndrome Scale (PANSS). Metabolites were measured using proton magnetic resonance spectroscopy, and quantified using internal water as reference. RESULTS: First-episode schizophrenia subjects revealed reduced GABA and myo-inositol (mI), and increased Glx and choline (Cho), compared to HC. No significant correlation was found between metabolite levels and PANSS scores. Receiver operator characteristics analyses showed Glx had higher sensitivity and specificity (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for differentiating schizophrenia patients from HC. Combined model of both GABA and Glx revealed the best sensitivity and specificity (89.5%, 100%). CONCLUSION: This study simultaneously showed reduction in GABA and elevation in Glx in first-episode schizophrenia subjects, and this might provide insights on explaining the disruption of modulation between GABAergic interneurons and glutamatergic neurons. Elevated Cho might indicate increased membrane turnover; whereas reduced mI might reflect dysfunction of the signal transduction pathway. In vivo Glx and GABA revealed their diagnostic potential for schizophrenia.

Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time.

The present study examined different types of neurological signs in patients with first-episode schizophrenia and their relationships with neurocognitive functions. Both cross-sectional and longitudinal designs were adopted with the use of the abridged Cambridge Neurological Inventory which comprises items capturing motor coordination, sensory integration and disinhibition. A total of 157 patients with first-episode schizophrenia were assessed at baseline and 101 of them were re-assessed at six-month interval. A structural equation model (SEM) with invariance model across time was used for data analysis. The model fitted well with the data at baseline assessment, X^2(21) = 21.78, p = 0.413, NFI = 0.95, NNFI = 1.00, CFI = 1.00, IFI = 1.00, RMSEA = 0.015. Subsequent SEM analysis with invariance model at six-month interval also demonstrated the same stable pattern across time and showed strong measurement invariance and structure invariance across time. Our findings suggest that neurological signs capture more or less the same construct captured by conventional neurocognitive tests in patients with schizophrenia. The measurement and structure of these relationships appear to be stable over time.

Theory of mind impairments in patients with first-episode schizophrenia and their unaffected siblings.

BACKGROUND: Theory of mind (ToM) impairment has been consistently demonstrated in patients with schizophrenia, but whether ToM impairments exist in unaffected siblings of patients with schizophrenia remains unclear. Few studies have examined the affective and cognitive components of ToM in schizophrenia. This study aimed to examine whether ToM impairments exist in patients with first-episode schizophrenia and their unaffected siblings, and whether there is any dissociation between the affective and cognitive components of ToM. METHOD: We adopted a family-based case-control design. Participants were 41 patients with first-episode schizophrenia, 43 unaffected siblings, and 42 healthy controls. The Yoni Task which measures the participants' ability to understand first- and second-order affective versus cognitive ToM and the Faux Pas Task which taps into integration of the affective and cognitive components of ToM were administered. Multivariate and univariate ANCOVAs were used to examine the group differences in ToM, while controlling for other neurocognitive functions. RESULTS: Compared with controls, patients with schizophrenia and their unaffected siblings performed poorer on the Faux Pas Task (p<0.001), with siblings having intermediate performance between patients and controls. Patients with schizophrenia performed worse than controls on second-order affective condition of the Yoni Task (p=0.004), but their unaffected siblings did not (p=0.063). We did not find any significant Group-by-Condition interaction in the Yoni Task (p=0.358). CONCLUSION: Patients with first-episode schizophrenia and their unaffected siblings exhibit ToM impairments, but no dissociation between affective and cognitive component of ToM was found. Our findings support the notion that ToM deficit may be a trait marker of schizophrenia.

Course of neurological soft signs in first-episode schizophrenia: Relationship with negative symptoms and cognitive performances.

This prospective study examined the course of neurological soft signs (NSS) in patients with first-episode schizophrenia and its relationship with negative symptoms and cognitive functions. One hundred and forty-five patients with first-episode schizophrenia were recruited, 29 were classified as having prominent negative symptoms. NSS and neuropsychological measures were administered to all patients and 62 healthy controls at baseline. Patients were then followed-up prospectively at six-month intervals for up to a year. Patients with prominent negative symptoms exhibited significantly more motor coordination signs and total NSS than patients without prominent negative symptoms. Patients with prominent negative symptoms performed worse than patients without negative symptoms in working memory functions but not other fronto-parietal or fronto-temporal functions. Linear growth model for binary data showed that the prominent negative symptoms were stable over time. Despite general improvement in NSS and neuropsychological functions, the prominent negative symptoms group still exhibited poorer motor coordination and higher levels of NSS, as well as poorer working memory than patients without prominent negative symptoms. Two distinct subtypes of first-episode patients could be distinguished by NSS and prominent negative symptoms.

Validation of the Chinese version of the Clinical Assessment Interview for Negative Symptoms (CAINS): a preliminary report.

The present study aimed to examine the psychometric properties of the Chinese version of the Clinical Assessment Interview for Negative Symptoms (CAINS). We recruited 68 patients with schizophrenia from the Chinese setting. The findings showed a generally consistent two-factor structure with the original version, namely "expression" and "motivation-pleasure." There is a minor cultural variation in perceiving these items in the Chinese culture. However, the present study demonstrated that the Chinese version of the CAINS appears to be a valid and reliable clinical tool for the assessment of negative symptoms in the Chinese setting.