Negative symptoms in treatment-resistant schizophrenia and its relationship with functioning.

BACKGROUND: Recent operational criteria for treatment-resistant schizophrenia (TRS) recognized positive and negative symptoms. TRS patients may have heterogeneity in negative symptoms, but empirical data were lacking. We aimed to characterize TRS patients based on negative symptoms using cluster analysis, and to examine between-cluster differences in social functioning. METHODS: We administered the Clinical Assessment Interview of Negative symptoms (CAINS), Brief Negative Symptom Scale (BNSS), the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functional Assessment (SOFAS to 126 TRS outpatients. All patients also completed the Temporal Experience of Pleasure Scale (TEPS), the Emotion Expressivity Scale (EES), and the Social Functional Scale (SFS). A two-stage hierarchical cluster analysis was performed with the CAINS, TEPS and EES as clustering variables. We validated the clusters using ANOVAs to compare group differences in the BNSS, PANSS, SOFAS and SFS. RESULTS: Clustering indices supported a 3-cluster solution. Clusters 1 (n = 46) and 3 (n = 16) exhibited higher CAINS scores than Cluster 2 (n = 64), and were negative-symptom TRS subtypes. Cluster 1 reported lower TEPS than Cluster 3; but Cluster 3 reported lower EES than Cluster 1. Upon validation, Clusters 1 and 3 exhibited higher BNSS scores than Cluster 2, but only Cluster 1 exhibited lower SOFAS and higher PANSS general symptoms than Cluster 2. Both Clusters 1 and 3 had higher self-report functioning than Cluster 2. CONCLUSION: We provided evidence for heterogeneity of negative symptoms in TRS. Negative symptoms can characterize TRS patients and predict functional outcome.

The Future-oriented Repetitive Thought (FoRT) scale: Validation in Chinese samples and application in the schizophrenia spectrum.

BACKGROUND: Repetitive thoughts are usually associated with psychopathology. The Future-oriented Repetitive Thought (FoRT) Scale is a measure designed to capture frequency of repetitive thought about positive and negative future events. However, the validity of the scale in Chinese population and its application in the schizophrenia spectrum have not been examined. METHODS: The current study aimed to examine the psychometric properties of the Chinese version of the FoRT scale and to apply it to the schizophrenia spectrum. In Study 1, three samples (total N = 1875) of university students were recruited for exploratory factor analysis, confirmatory factor analysis, and validity test, respectively. In Study 2, we identified subsamples with high schizotypal traits (N = 89) and low schizotypal traits (N = 89), and recruited 36 inpatients with schizophrenia and 41 matched healthy controls. RESULTS: The three-factor (pessimistic repetitive future thinking, repetitive thinking about future goals, and positive indulging about the future) structure of the FoRT scale with one item deleted, fitted the Chinese samples. And the scale could distinguish patients with schizophrenia and individuals with high schizotypal traits from controls. CONCLUSION: These findings support that the Chinese version of the FoRT scale is a valid tool and provide evidence for the potential applications in the schizophrenia spectrum.

Neuropsychology and Neurobiology of Negative Schizotypy: A Selective Review.

Schizotypy refers to a latent personality organization that reflects liability to schizophrenia. Because schizotypy is a multidimensional construct, people with schizotypy vary in behavioral and neurobiological features. In this article, we selectively review the neuropsychological and neurobiological profiles of people with schizotypy, with a focus on negative schizotypy. Empirical evidence is presented for alterations of neuropsychological performance in negative schizotypy. We also cover the Research Domain Criteria domains of positive valence, social process, and sensorimotor systems. Moreover, we systematically summarize the neurobiological correlates of negative schizotypy at the structural, resting-state, and task-based neural levels, as well as the neurochemical level. The convergence and inconsistency of the evidence are critically reviewed. Regarding theoretical and clinical implications, we argue that negative schizotypy represents a useful organizational framework for studying neuropsychology and neurobiology across different psychiatric disorders.

This perspective paper provides empirical evidence to show that schizotypy, and especially negative schizotypy, are associated with alterations of positive valence, social process, and sensorimotor systems domains within the Research Domain Criteria (RDoC). This perspective paper also systematically summarizes the neurobiological correlates of negative schizotypy at the structural, resting-state, and task-based neural levels, as well as the neurochemical level. We argue that negative schizotypy represents a useful organizational framework for studying neuropsychology and neurobiology across different psychiatric disorders.

Self-perceived upper extremity motor function predicts health-related quality of life in chronic stroke survivors.

PURPOSE: To examine whether the Upper Extremity Functional Index (UEFI) score independently contributes to the Stroke Impact Scale (SIS) score and quantified its relative contribution to SIS scores in chronic stroke survivors. MATERIALS AND METHODS: A cross-sectional study in a university-based rehabilitation centre with people with chronic stroke (N = 95) aged ≥ 50 years. The outcome measures included paretic hand grip strength, Fugl-Meyer Upper Extremity Assessment (FMA-UE), Wolf Motor Function Test (WMFT), UEFI, and SIS. RESULTS: Correlation analysis revealed that paretic hand grip strength, FMA-UE, UEFI, and WMFT scores exhibited a significant moderate positive correlation with SIS scores (r = 0.544-0.687, p < 0.001). The results of a regression model indicated that after adjustment for demographic factors and stroke-related impairments, the UEFI scores remained independently associated with SIS scores, accounting for 18.8% of the variance. The entire model explained 60.3% of the variance in SIS scores. CONCLUSIONS: Self-perceived UE motor function is a crucial component to be included in rehabilitation programmes aimed at enhancing quality of life and participation among chronic stroke survivors.

Observation-based outcome measures, e.g., Fugl­Meyer Assessment for Upper Extremity (FMA-UE), Wolf Motor Function Test (WMFT) could not predict the health-related quality of life (Stroke Impact scale (SIS)) in chronic stroke survivors in our study, which was contradictory with current studies.A self-perceived outcome measure to evaluate upper extremity function (Upper Extremity Functional Index (UEFI)) could independently predict the health-related quality of life (SIS), accounting for 18.8% of the variance.Our study demonstrated that self-perceived UE motor function would be an important component to optimize the rehabilitation programmes aimed at enhancing quality of life and social participation among chronic stroke survivors.

Neural substrates of the interaction between effort-expenditure reward decision-making and outcome anticipation.

OBJECTIVE: Reward anticipation is important for future decision-making, possibly due to re-evaluation of prior decisions. However, the exact relationship between reward anticipation and prior effort-expenditure decision-making, and its neural substrates are unknown. METHOD: Thirty-three healthy participants underwent fMRI scanning while performing the Effort-based Pleasure Experience Task (E-pet). Participants were required to make effort-expenditure decisions and anticipate the reward. RESULTS: We found that stronger anticipatory activation at the posterior cingulate cortex was correlated with slower reaction time while making decisions with a high-probability of reward. Moreover, the substantia nigra was significantly activated in the prior decision-making phase, and involved in reward-anticipation in view of its strengthened functional connectivity with the mammillary body and the putamen in trial conditions with a high probability of reward. CONCLUSIONS: These findings support the role of reward anticipation in re-evaluating decisions based on the brain-behaviour correlation. Moreover, the study revealed the neural interaction between reward anticipation and decision-making.

Exploring phenotypic overlap across schizotypy and autism spectrum conditions in American and Chinese young adults.

Competing theories have been proposed to explain the considerable overlap in social-cognitive features and risk factors across schizotypy and autism spectrum conditions (ASCs). Six previous factor analyses have been reported in the literature, yet all have major limitations; evidence for the clear superiority of any of the competing theories is insufficient and warrants further investigation. The primary aim of the present research was to identify dimensions that cut across schizotypy and ASCs while addressing limitations of past research. Data were collected from three independent samples (n = 1006, 544, and 2469) in the U.S. and China using the Autism-Spectrum Quotient, the Schizotypal Personality Questionnaire, and the Wisconsin Schizotypy Scales. Exploratory factor analyses in Sample 1 identified an interpretable three-factor structure, which was replicated in Samples 2 and 3 using confirmatory factor analyses. We found consistent evidence for three dimensions (Aberrant Salience, Asociality, and Concrete Thinking) underlying schizotypy and ASCs. This three-dimension model is consistent with a common vulnerability model of schizotypy and ASCs. Implications of these findings for the schizotypy and ASCs literature are discussed.

Empathic accuracy in individuals with schizotypal personality traits.

Empirical research using the Empathic Accuracy Task (EAT) has suggested that schizophrenia patients and people with schizotypal personality disorder exhibit lower empathic accuracy than healthy people. However, empathic accuracy in a subclinical sample with high levels of schizotypy has seldom been studied. Our study aimed to investigate empathy in a subclinical sample using the Chinese version of the EAT and a self-report empathy measure. Forty participants with high levels of schizotypy (HS participants) and 40 with low levels of schizotypy (LS participants), as measured by the Schizotypal Personality Questionnaire (SPQ), were recruited. All participants completed the Chinese version of the EAT and the self-report Questionnaire of Cognitive and Affective Empathy. Empathic accuracy (EA) scores and the intra-individual variability of EA scores were calculated. Independent samples t tests and Pearson correlation analyses were performed to examine group differences in empathy and the relationship between empathy and schizotypy respectively. HS participants exhibited reduced EA for both positive and negative videos, and larger intra-individual variability of EA for negative videos than LS participants. However, HS and LS participants did not differ in self-report cognitive empathy. Moreover, the interpersonal dimension of the SPQ was negatively correlated with EAT performance and self-report cognitive empathy in LS participants. Individuals with HS show poorer performance-based EA but relatively intact self-report cognitive empathy. This study provides empirical evidence for the ontogeny of empathy deficits in subclinical populations at risk of developing schizophrenia, supporting early interventions for social cognitive deficits.

Interoception, somatic symptoms, and somatization tendency in Chinese individuals with subsyndromal depression: A follow-up study.

Interoception refers to the sensation and perception of internal bodily sensations, and may be related to depressive symptoms. Schemata concerning the body vary across different cultures and may influence interoception and symptom presentations of depression. This study explored the relationship between interoception, depressive symptoms, and schema of somatic focus in Chinese people with subsyndromal depression. Thirty-nine individuals with subsyndromal depression (SD) and 40 healthy controls (HCs) were assessed at baseline and after 3 months. Participants completed the self-report questionnaires for assessing interoceptive sensibility, somatic and psychological symptoms of depression, and somatization tendency. They also completed the heartbeat perception behavioral task for estimating interoceptive accuracy. The results showed that both the SD and the HC groups showed similar interoceptive accuracy, although the SD group showed heightened interoceptive sensibility. The discrepancy between interoceptive sensibility and interoceptive accuracy is termed the interoceptive trait prediction error (ITPE). The ITPE was positive in SD participants but was negative in HCs. In the entire sample, interoceptive sensibility and the ITPE were correlated with somatic symptoms rather than with psychological symptoms of depression. Interoceptive sensibility partially mediated the relationship between somatization tendency and somatic symptoms, after controlling for psychological symptoms of depression. These results remained stable after 3 months. The shortcomings of the present study were a lack of clinical interview to ascertain diagnosis and a short follow-up duration. In conclusion, our study suggests that altered interoception occurs in subsyndromal depression. Interoception is related to somatic symptoms of depression. The schema of body was related to depressive symptoms, partially through interoception, in Chinese people with subsyndromal depression.

Individuals with high levels of autistic traits exhibit impaired cognitive but not affective theory of mind and empathy.

Theory of mind (ToM) and empathy are considered key components of social cognition that are often impaired in individuals with autism spectrum disorders (ASD). However, it remains unclear whether individuals with high levels of autistic traits exhibit similar impairments in these two functions. This study examined the affective and cognitive domains of ToM and empathy in individuals with high levels of autistic traits. We recruited 84 participants with high levels and 78 participants with low levels of autistic traits to complete a set of self-reported checklists and performance-based tasks capturing affective and cognitive components of ToM and empathy. The results showed that participants with high levels of autistic traits exhibited significant impairments in cognitive but not in affective ToM and empathy compared with their counterparts with low levels of autistic traits. We also found that empathy impairments in people with high levels of autistic traits were confounded by alexithymia and depressive traits.

Effects of mirror therapy with electrical stimulation for upper limb recovery in people with stroke: a systematic review and meta-analysis.

PURPOSE: To provide updated evidence about the effects of MT with ES for recovering upper extremities motor function in people with stroke. METHODS: Systematic review and meta-analysis were completed. Methodological quality was assessed using the version 2 of the Cochrane risk-of-bias tool. The GRADE approach was employed to assess the certainty of evidence. RESULTS: A total of 16 trials with 773 participants were included in this review. The results demonstrated that MT with ES was more effective than sham (standardized mean difference [SMD], 1.89 [1.52-2.26]) and ES alone (SMD, 0.42 [0.11-0.73]) with low quality of evidence, or MT alone (SMD, 0.47[0.04-0.89]) with low quality of evidence for improving upper extremity motor control assessed using Fugl-Meyer Assessment. MT with ES had significant improvement of (MD, 6.47 [1.92-11.01]) the upper extremity gross gripping function assessed using the Action Research Arm Test compared with MT alone with low quality of evidence. MT combined with ES was more effective than sham group (SMD, 1.17 [0.42-1.93) for improving the ability to perform activities of daily living with low quality of evidence assessed using Motor Activity Log. CONCLUSION: MT with ES may be effective in improving upper limb motor recovery in people with stroke.

Combining Mirror Therapy (MT) and Electrical Stimulation (ES) modality could improve upper limb motor control, gross gripping function, and performance in ADLs based on ICF for people with stroke.Those individuals with subacute stroke are recommended as the optimal target group for the combined MT and ES.

The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study.

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Identifying subgroups of attention-deficit/hyperactivity disorder from the psychopathological and neuropsychological profiles.

The Research Domain Criteria (RDoC) advocates the dimensional approach in characterizing mental disorders. We followed RDoC to characterize children with ADHD using profiling based on the cognitive and psychopathological domains. We aimed to identify and validate ADHD subtypes with different clinical characteristics and functional impairments. We recruited 362 drug-naïve children with ADHD and 103 typically developing controls. The cluster analysis was used to identify subgroups based on the Child Behaviour Checklist (CBCL) and the Behaviour Rating Inventory of Executive Function (BRIEF). The subgroups' clinical characteristics and functional impairments were assessed using the WEISS Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Conners Parent Symptom Questionnaire (PSQ). The cluster analysis yielded four subgroups: (1) ADHD with severe impairment in psychopathology and executive functions (EF), (2) ADHD with mild executive dysfunctions and normal-level psychopathology, (3) ADHD with severe externalizing problems and (4) ADHD with severe executive dysfunctions. These subgroups showed different clinical characteristics and degrees of functional impairment. The EF impairment group displayed more serious learning problems and worse life skills than the externalizing group. The two groups with externalizing problems (i.e. the severe impairment group and the externalizing group) both exhibited higher rates of the combined subtype of ADHD and higher rates of comorbid ODD. Different subtypes of ADHD displayed different profiles of internalizing and externalizing problems and levels of executive dysfunctions. In particular, the subtype with severe impairment in EF exhibited more learning problems and worse life skills, suggesting EF is a critical target for intervention in children with ADHD.

Social and non-social reward processing in subclinical depression.

This study applied two incentive delay tasks involving social and non-social incentive types to 76 pairs of participants with high and low depressive symptoms. The results suggest that higher levels of depressive symptoms are correlated with abnormalities in social and non-social reward processing even in the healthy populations.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

Unveiling the potential of machine learning in schizophrenia diagnosis: A meta-analytic study of task-based neuroimaging data.

The emergence of machine learning (ML) techniques has opened up new avenues for identifying biomarkers associated with schizophrenia (SCZ) using task-related fMRI (t-fMRI) designs. To evaluate the effectiveness of this approach, we conducted a comprehensive meta-analysis of 31 t-fMRI studies using a bivariate model. Our findings revealed a high overall sensitivity of 0.83 and specificity of 0.82 for t-fMRI studies. Notably, neuropsychological domains modulated the classification performance, with selective attention demonstrating a significantly higher specificity than working memory (ß = 0.98, z = 2.11, P = 0.04). Studies involving older, chronic patients with SCZ reported higher sensitivity (P <0.015) and specificity (P <0.001) than those involving younger, first-episode patients or high-risk individuals for psychosis. Additionally, we found that the severity of negative symptoms was positively associated with the specificity of the classification model (ß = 7.19, z = 2.20, P = 0.03). Taken together, these results support the potential of using task-based fMRI data in combination with machine learning techniques to identify biomarkers related to symptom outcomes in SCZ, providing a promising avenue for improving diagnostic accuracy and treatment efficacy. Future attempts to deploy ML classification should consider the factors of algorithm choice, data quality and quantity, as well as issues related to generalization.

Range adaptation in schizophrenia: A one-year longitudinal study.

Range adaptation refers to the representation of a stimulus value based on its relative position in the range of pre-experienced values. Altered range adaptation in value representation may be related to motivation and pleasure (MAP) deficit in schizophrenia (SCZ). This follow-up study examined the relationship between range adaptation performance and MAP symptoms in SCZ patients. We recruited 26 schizophrenia patients and followed them for 1 year. They completed an experimental task for estimating their range adaptation to outcome value (OV) and expected value (EV) at baseline and after 1 year. At baseline, we found a marginally significant and negative correlation between OV adaptation and avolition symptoms in SCZ patients. Moreover, the 1-year change of EV adaptation was significantly and negatively correlated with the change of self-report pleasure experience. Our results suggest that range adaptation may track the variations of MAP symptoms in SCZ.

Range adaptive value representations in schizophrenia and major depression.

Anhedonia and amotivation are core symptoms of schizophrenia (SCZ) and major depressive disorder (MDD). Reward processing involves constructing and contrasting the representations for expected value (EV) and outcome value (OV) of a given stimulus, a phenomenon termed range adaptation. Impaired range adaptation can lead to anhedonia and amotivation. This study aimed to examine range adaptation in SCZ patients and MDD patients. Fifty SCZ, 46 MDD patients and 56 controls completed the Effort-based Pleasure Experience Task to measure EV and OV adaptation. SCZ and MDD patients showed altered range adaptation, albeit in different patterns. SCZ patients exhibited over-adaptation to OV and reduced adaptation to EV. By contrast, MDD patients exhibited diminished OV adaptation but intact EV adaptation. Both OV and EV adaptation were correlated with anhedonia and amotivation in SCZ and MDD. Taken together, our findings suggest that range adaptation is altered in both SCZ and MDD patients. Associations of OV and EV adaptation with anhedonia and amotivation were consistently found in SCZ and MDD patients. Impaired range adaptation in SCZ and MDD patients may be putative neural mechanisms and potential intervention targets for anhedonia and amotivation.