Negative schizotypal traits predict the reduction of reward motivation in effort-reward imbalance.

The schizotypy construct is useful for studying the effects of environmental stress on development of subclinical negative symptoms. The relationship among self-report motivation, effort-reward imbalance (ERI), and schizotypal features has seldom been studied. We aimed to examine the possible moderation effect of schizotypal traits on ERI and reward motivation. Eight-hundred-and-forty-three college students were recruited online to complete a set of self-reported measures capturing schizotypal traits, effort-reward imbalance and reward motivation, namely the Schizotypal Personality Questionnaire (SPQ), the Effort-Reward Imbalance-School Version Questionnaire (C-ERI-S) and the Motivation and Pleasure Scale-Self Report (MAP-SR). We conducted multiple linear regression to construct models to investigate the moderating effects of schizotypal traits on the relationship between ERI and reward motivation. Stressful ERI situation predicted the reduction of reward motivation. Negative schizotypal traits showed a significant negative moderating effect on the relationship between ERI and reward motivation, while positive and disorganized schizotypal traits had significant positive moderating effects. Schizotypal traits subtypes differently moderate the relationship between ERI and reward motivation. Only negative schizotypal traits and stressful ERI situation together have negative impact on reward motivation.

Reward motivation adaptation in people with negative schizotypal features: development of a novel behavioural paradigm and identifying its neural correlates using resting-state functional connectivity analysis.

Reward motivation in individuals with high levels of negative schizotypal traits (NS) has been found to be lower than that in their counterparts. But it is unclear that whether their reward motivation adaptively changes with external effort-reward ratio, and what resting-state functional connectivity (rsFC) is associated with this change. Thirty-five individuals with high levels of NS and 44 individuals with low levels of NS were recruited. A 3T resting-state functional brain scan and a novel reward motivation adaptation behavioural task were administrated in all participants. The behavioural task was manipulated with three conditions (effort > reward condition vs. effort < reward condition vs. effort = reward condition). Under each condition were rated 'wanting' and 'liking' for rewards. The seed-based voxel-wise rsFC analysis was conducted to explore the rsFCs associated with the 'wanting' and 'liking' ratings in individuals with high levels of NS. 'Wanting' and 'liking' ratings of individuals with high levels of NS significantly declined in the effort > reward condition but did not rebound as high as their counterparts in the effort < reward condition. The rsFCs in NS group associated with these ratings were altered. The altered rsFCs in NS group involved regions in the prefrontal lobe, dopaminergic brain regions (ventral tegmental area, substantia nigra), hippocampus, thalamus and cerebellum. Individuals with high levels of NS manifested their reward motivation adaptation impairment as a failure of adjustment adaptively during effort-reward imbalance condition and altered rsFCs in prefrontal, dopaminergic and other brain regions.

Altered neural mechanism of social reward anticipation in individuals with schizophrenia and social anhedonia.

Altered social reward anticipation could be found in schizophrenia (SCZ) patients and individuals with high levels of social anhedonia (SA). However, few research investigated the putative neural processing for altered social reward anticipation in these populations on the SCZ spectrum. This study aimed to examine the underlying neural mechanisms of social reward anticipation in these populations. Twenty-three SCZ patients and 17 healthy controls (HC), 37 SA individuals and 50 respective HCs completed the Social Incentive Delay (SID) imaging task while they were undertaking MRI brain scans. We used the group contrast to examine the alterations of BOLD activation and functional connectivity (FC, psychophysiological interactions analysis). We then characterized the beta-series social brain network (SBN) based on the meta-analysis results from NeuroSynth and examined their prediction effects on real-life social network (SN) characteristics using the partial least squared regression analysis. The results showed that SCZ patients exhibited hypo-activation of the left medial frontal gyrus and the negative FCs with the left parietal regions, while individuals with SA showed the hyper-activation of the left middle frontal gyrus when anticipating social reward. For the beta-series SBNs, SCZ patients had strengthened cerebellum-temporal FCs, while SA individuals had strengthened left frontal regions FCs. However, such FCs of the SBN failed to predict the real-life SN characteristics. These preliminary findings suggested that SCZ patients and SA individuals appear to exhibit altered neural processing for social reward anticipation, and such neural activities showed a weakened association with real-life SN characteristics.

A network analysis of interoception, self-awareness, empathy, alexithymia, and autistic traits.

Altered interoception has been consistently found in people with autism spectrum disorder (ASD), and this impairment may contribute to social cognitive dysfunctions. However, little is known regarding the intercorrelations between interoceptive sensibility, autistic, alexithymic, empathic, and self-related traits. We recruited 1360 non-clinical college students and adults to investigate the complex inter-relationship between these variables using network analysis. The resultant network revealed patterns connecting autistic traits to interoceptive sensibility, empathy, alexithymia, and self-awareness, with reasonable stability and test-retest consistency. The node of alexithymia exhibited the highest centrality and expected influence. As revealed by the network comparison test, networks constructed in high- and low-autistic subgroups were comparable in global strength and structure. Our findings suggested that alexithymia serves as an important node, bridging interoceptive deficits, self-awareness, and empathic impairments of autism spectrum disorder. The co-morbidity of alexithymia should be considered carefully in future studies of interoceptive impairments and social deficits in ASD.

Co-occurrence of schizo-obsessive traits and its correlation with altered executive control network functional connectivity.

The prevalence of obsessive-compulsive symptoms (OCS) in schizophrenia patients is as around 30%. Evidence suggested that mild OCS could reduce symptoms of schizophrenia, supporting the presence of compensatory functions. However, severe OCS could aggravate various impairments in schizophrenia patients, supporting the "double jeopardy hypothesis". Patients with schizo-obsessive comorbidity, schizophrenia patients and obsessive-compulsive disorder patients have been found to have similarities in executive dysfunctions and altered resting-state functional connectivity within the executive control network (ECN). Executive functions could be associated with the ECN. However, little is known as to whether such overlap exists in the subclinical populations of individuals with schizo-obsessive traits (SOT), schizotypal individuals and individuals with high levels of obsessive-compulsive symptoms (OCS). In this study, we recruited 30 schizotypal individuals, 25 individuals with OCS, 29 individuals with SOT and 29 controls for a resting-state ECN-related functional connectivity (rsFC) and a go/shift/no-go task. We found that individuals with SOT exhibited increased rsFC within the ECN compared with controls, while schizotypal individuals exhibited the opposite. Individuals with OCS exhibited decreased rsFC within the ECN and between the ECN and the default mode network (DMN), relative to controls. No significant correlational results between altered rsFC related to the ECN with executive function performance were found after corrections for multiple comparisons in three subclinical groups. Our findings showed that individuals with SOT had increased rsFC within the ECN, while schizotypal individuals and individuals with OCS showed the opposite. Our findings provide evidence for possible neural substrates of subclinical comorbidity of OCS and schizotypy.

Negative belief-updating bias for positive daily life events in individuals with schizophrenia and social anhedonia.

INTRODUCTION: Low-pleasure beliefs are found in both patients with schizophrenia (SZ) and individuals with high social anhedonia (SocAnh), and are associated with anhedonia. However, little is known about the development and maintenance of these low-pleasure beliefs in the clinical and subclinical populations. We investigated whether patients with SZ and individuals with high SocAnh have deficits in updating their beliefs, which may contribute to the understanding of the formation and maintenance of low-pleasure beliefs. METHODS: The Modified Belief Updating Task was administered to assess belief-updating patterns in a clinical sample (36 SZ patients and 30 matched controls) and a subclinical sample (27 individuals with high SocAnh and 30 matched controls). RESULTS: We found that compared with controls, SZ patients updated their beliefs to a greater extent and more frequently when receiving bad news for positive life events, but not for negative life events. Moreover, individuals with high SocAnh also exhibited similar patterns in updating their beliefs for positive life events after controlling depressive symptoms. CONCLUSIONS: Our findings suggest that negative belief-updating patterns for positive events may play an important role in the formation and maintenance of low-pleasure beliefs in patients with SZ and individuals with high SocAnh.

The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

4ß-Hydroxywithanolide E from Goldenberry (Whole Fruits of Physalis peruviana L.) as a Promising Agent against Chronic Obstructive Pulmonary Disease.

Environmental toxicant- and oxidant-induced [e.g., cigarette smoke (CS)] respiratory oxidative stress and inflammatory response play a vital role in the onset and progression of COPD. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents an important mechanism for regulating intracellular oxidative stress and inflammatory response and is a promising target for developing agents against COPD. Herein, a bioactivity-guided purification of goldenberry (whole fruits of Physalis peruviana L.) led to the isolation of a novel and potent Nrf2 activator 4ß-hydroxywithanolide E (4ß-HWE). Our study indicated that (i) 4ß-HWE activated the Nrf2-mediated defensive response through interrupting Nrf2-Keap1 protein-protein interaction (PPI) via modification of Cys151 and Cys288 cysteine residues in Keap1 and accordingly suppressing the ubiquitination of Nrf2. (ii) 4ß-HWE enhanced intracellular antioxidant capacity and inhibited oxidative stress in normal human lung epithelial Beas-2B cells and wild-type AB zebrafish. (iii) 4ß-HWE blocked LPS-stimulated inflammatory response and inhibited LPS-stimulated NF-κB activation in RAW 264.7 murine macrophages. (iv) 4ß-HWE effectively suppressed oxidative stress and inflammatory response in a CS-induced mice model of pulmonary injury. Collectively, these results display the feasibility of using 4ß-HWE to prevent or alleviate the pathological progression of COPD and suggest that 4ß-HWE is a candidate or a leading molecule against COPD.

Chemical Constituents from Physalis Calyx seu Fructus and Their Inhibitory Effects against Oxidative Stress and Inflammatory Response.

Physalis Calyx seu Fructus, a traditional Chinese medicine consisting of the calyxes and fruits of Physalis alkekengi var. franchetii, has been used as therapy for inflammation-related respiratory diseases such as excessive phlegm, cough, sore throat, and pharyngitis for a long history in China. The aim of the present study was to investigate the chemical constituents of Physalis Calyx seu Fructus and identify the bioactive constituents responsible for its traditional application as therapy for inflammation-related diseases. In the present study, one new phenylpropanoid (1: ), two new steroids (17: and 18: ), together with 55 known constituents have been purified from the EtOH extract of Physalis Calyx seu Fructus. Among them, seven and twelve known constituents were isolated for the first time from Physalis Calyx seu Fructus and the genus Physalis, respectively. Fourteen constituents, including steroids [physalins (5:  - 9, 12:  - 14: , and 15: ) and ergostane (21: )], a sesquiterpenoid (35: ), alkaloids (36: and 37: ), and a flavonoid (44: ), showed inhibitory effects against oxidative stress. Ten constituents, including steroids (5, 6, 8, 13: , and 15: ), sesquiterpenoids (34: and 35: ), alkaloids (37: and 41: ), and a flavonoid (43: ), were found be potential anti-inflammatory constituents of this medicinal plant. The inhibition of oxidative stress and inflammatory response may be related to the regulation of Nrf2 and nuclear factor-κB pathways. The ethnomedical use of Physalis Calyx seu Fructus as a treatment for respiratory diseases might be attributed to the combined inhibitory effects of steroids, alkaloids, sesquiterpenoids, and flavonoids against oxidative stress and inflammatory response.

The remediation effects of working memory training in schizophrenia patients with prominent negative symptoms.

Introduction: Negative symptoms, particularly amotivation and anhedonia, are important predictors of poor functional outcome in patients with schizophrenia. There has been interest in the efficacy and mechanism of non-pharmacological interventions to alleviate these symptoms. The present study aimed to examine the remediation effect of working memory (WM) training in patients with schizophrenia with prominent negative symptoms.Methods: Thirty-one schizophrenia patients with prominent negative symptoms were recruited and assigned to either a WM training group or a treatment-as-usual (TAU) control group. The WM training group underwent 20 sessions of training using the dual n-back task over one month. A functional neuroimaging paradigm of the Affective Incentive Delay (AID) task was administered before and after the training intervention to evaluate the remediation effect of the intervention.Results: Our results showed that the WM training group demonstrated significant improvement in the WM training task and inattention symptoms. Compared with the TAU group, increased brain activations were observed at the right insula and the right frontal sub-gyral after WM training in the training group.Conclusions: These findings support the efficacy of WM training in ameliorating hedonic dysfunction in schizophrenia patients with prominent negative symptoms.

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.

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.

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.

Neural correlates of audiovisual speech synchrony perception and its relationship with autistic traits.

The anterior insula (AI) has the central role in coordinating attention and integrating information from multiple sensory modalities. AI dysfunction may contribute to both sensory and social impairments in autism spectrum disorder (ASD). Little is known regarding the brain mechanisms that guide multisensory integration, and how such neural activity might be affected by autistic-like symptoms in the general population. In this study, 72 healthy young adults performed an audiovisual speech synchrony judgment (SJ) task during fMRI scanning. We aimed to investigate the SJ-related brain activations and connectivity, with a focus on the AI. Compared with synchronous speech, asynchrony perception triggered stronger activations in the bilateral AI, and other frontal-cingulate-parietal regions. In contrast, synchronous perception resulted in greater involvement of the primary auditory and visual areas, indicating multisensory validation and fusion. Moreover, the AI demonstrated a stronger connection with the anterior cingulate gyrus (ACC) in the audiovisual asynchronous (vs. synchronous) condition. To facilitate asynchrony detection, the AI may integrate auditory and visual speech stimuli, and generate a control signal to the ACC that further supports conflict-resolving and response selection. Correlation analysis, however, suggested that audiovisual synchrony perception and its related AI activation and connectivity did not significantly vary with different levels of autistic traits. These findings provide novel evidence for the neural mechanisms underlying multisensory temporal processing in healthy people. Future research should examine whether such findings would be extended to ASD patients.

The prediction of effort-reward imbalance for reward motivation.

This sequential mediation analysis study examined how the baseline effort-reward imbalance (ERI) would predict reward motivation 1 year later in 435 college students. We found that negative/disorganized schizotypal traits and anticipatory pleasure experience together mediate the prediction of ERI for reward motivation.

Emotional subtypes in patients with depression: A cluster analysis.

Major depressive disorder (MDD) is associated with deficits in emotion experience, expression and regulation. Whilst emotion regulation deficits prolong MDD, emotion expression influences symptomatic presentations, and anticipatory pleasure deficits predict recurrence risk. Profiling MDD patients from an emotion componential perspective can characterize subtypes with different clinical and functional outcomes. This study aimed to investigate emotional subtypes of MDD. A two-stage cluster analysis applied to 150 MDD patients. Clustering variables included emotion experience measured by Temporal Experience of Pleasure Scale, emotion expression measured by Toronto Alexithymia Scale, and emotion regulation measured by Emotion Regulation Questionnaire. We validated the resultant clusters by comparing their symptoms and functioning with that of 50 controls. Cluster 1 (n = 50) exhibited intact emotion experience and expression yet adopted reappraisal rather than suppression strategy, whereas Cluster 2 (n = 66) exhibited generalized emotional deficits. Cluster 3 (n = 34) exhibited emotion expression deficits and adopted both reappraisal and suppression strategies. On validation, Cluster 2 exhibited the worst, but Cluster 1 exhibited the least symptoms and social functioning impairments. Cluster 3 was intermediate among the two other subtypes. Our findings support the existence of different emotional subtypes in MDD patients, and have clinical and theoretical implications for developing future specific treatments for MDD.

Relationship Between Interoception and Autistic Traits: A Resting-State Functional Connectivity Study.

Interoception, the sense of the physiological condition of our body, is impaired in individuals with autism spectrum disorders. Evidence suggests that subclinical autistic traits are mild manifestations of autistic symptoms, present in the general population. We examined the resting-state functional connectivity (rsFC) associating with interoception and autistic traits in 62 healthy young adults. Autistic traits correlated negatively with the rsFC between the lateral ventral anterior insula and anterior cingulate cortex. Interoceptive accuracy and sensibility correlated positively with the rsFC between interoceptive brain networks and the cerebellum, supplementary motor area, and visual regions. The results suggest that a negative relationship between interoception and autistic traits is largely accounted for by both self-report measures and decreased rsFC amongst the interoceptive brain network.

Characterizing emotion profiles in non-clinical population: A cluster analytical study.

Emotion processing and beliefs about pleasure can influence the development and severity of depressive symptoms. This cluster analysis study aimed to profile a large sample of college students using pleasure experience, emotion expression and regulation as well as beliefs about pleasure. We also aimed to validate the resultant clusters in terms of depressive symptoms. A set of checklists capturing beliefs about pleasure and the three facets of emotion processing was administered to 1028 college students. A two-stage cluster analysis was used to analyze the profile of these emotional aspects in these college students. Our results showed that a three-cluster solution best fit the data. Cluster 1 (n = 536) was characterized by moderate levels of beliefs about pleasure, pleasure experience, emotion expression, and regulation; Cluster 2 (n = 402) was characterized by generally high levels of beliefs about pleasure, pleasure experience, emotion expression, and regulation; Cluster 3 (n = 90) was characterized by relatively low levels of beliefs about pleasure, pleasure experience, emotion expression, and regulation. The three clusters differed significantly in the severity of depressive symptoms. Our findings suggest the existence of three emotional subtypes, which may be useful in early detection of youth at risk of developing depression.

Relationships between childhood trauma and dimensional schizotypy: A network analysis and replication.

OBJECTIVES: Childhood trauma (CT) has been found to increase the risk of developing schizophrenia and other psychiatric disorders. Little is known regarding the complex interplay between CT, subclinical psychotic, and affective symptoms in the general population. This cross-sectional study adopted network analysis to examine such a complex relationship. We hypothesized that CT would show strong connections with schizotypy dimensions, and the high schizotypy subgroup would show a network with higher global strength compared with the low schizotypy subgroup. METHODS: A total of 1813 college students completed a set of self-report questionnaires measuring CT, schizotypal features, bipolar traits, and depressive symptoms. The subscales of these questionnaires were used as nodes, and the partial correlations between nodes were used as edges to construct a network. Network Comparison Tests were used to investigate the differences between participants with high schizotypy and low schizotypy. An independent sample (n = 427) was used to examine the replicability of the results. RESULTS: Findings from the main dataset showed that CT was closely connected with schizotypy and motivation, after controlling for the inter-relationships between all nodes in the network. Relative to the low schizotypy subgroup, the network of the high schizotypy subgroup showed higher global strength. The two subgroups did not differ in network structure. Network analysis using the replication dataset showed comparable global strength and network structure. CONCLUSIONS: Our findings support specific links between CT and schizotypy dimensions in healthy youth populations, and such links appear to become stronger in those with high schizotypy.