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.

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.

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. METHODS: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. RESULTS: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 (PBonferroni < 0.001). Amisulpride group had a higher treatment response rate (P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. CONCLUSION: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974.

Revisiting the latent structure of negative symptoms in schizophrenia: Evidence from two second-generation clinical assessments.

BACKGROUND: Negative symptoms are core symptom of schizophrenia, and many previous research studied the latent structure of negative symptoms based on a single measurement scale. Applying two second-generation negative symptom scales to the same sample can address measurement-invariance of latent structure. METHODS: Three-hundred-and-five schizophrenia patients were assessed using the CAINS and the BNSS. Confirmatory Factor Analysis (CFA) tested four competing factor-models: (1) a 1-factor model; (2) a 2-factor model comprising the motivation and pleasure (MAP) domain and the diminished expression (EXP) domain; (3) a 5-factor model comprising anhedonia, avolition, asociality, blunted affect and alogia; (4) a hierarchical model comprising the "first-order" 5-domain factors and the "second-order" MAP & EXP factors. RESULTS: The CFA results for the data of the CAINS showed that the 2-factor model had the best data fit over the other competing models. The CFA using the BNSS data in the same sample also supported the superiority of the 2-factor model. Lastly, after combining the items of the BNSS and CAINS together in the same sample for CFA, the 2-factor model prevailed over the other competing models. CONCLUSIONS: The 2-factor model appears to be measurement-invariant latent structure of negative symptoms. The novel method of combining the items of the CAINS and BNSS might have circumvented the possible imperfect construct of a single scale. Our findings support the MAP and EXP factors as the latent structure for negative symptoms.

Emotion Context Insensitivity is generalized in individuals with major depressive disorder but not in those with subclinical depression.

BACKGROUND: Depressed individuals experience deficits in emotional reactivity. One well-established theory is the Emotion Context Insensitivity (ECI) theory. To better understand impairments in emotional reactivity, we investigated whether the ECI theory is applicable to anticipatory, consummatory, and remembered affect, in both clinical and subclinical depression. METHODS: Participants were divided into four groups: Major Depressive Disorder Group (MDD, N = 60), Control Group for MDD (ControlMDD, N = 50), Subclinical Depression Group (SD, N = 56), and Control Group for SD (ControlSD, N = 56). The Hamilton Depression Rating Scale and the Beck Depression Inventory were used to assess the severity of depression and anhedonia symptoms. The Monetary Incentive Delay Task evaluated participants' affective responses towards monetary stimuli. RESULTS: The MDD group was more insensitive to both monetary reward and loss across most types of affect than was the control group. Compared with the controls, the SD group exhibited lower reactivity in anticipatory positive affect but enhanced reactivity in consummatory positive, anticipatory, and remembered negative affect. LIMITATIONS: Emotional affect was evaluated by subjective ratings, which may lack objectivity. Additionally, laboratory settings and monetary rewards used in this study may cause the results less generalized to daily life and to other types of rewards. CONCLUSION: The pattern of emotional reactivity in the MDD group was partly consistent with the ECI theory, whereas the SD group showed greater arousal and instability of emotional reactions. These different patterns could facilitate the understanding of emotional reactivity and develop further treatments across the course of depression.

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.

Revisiting anticipatory hedonic processing in patients with schizophrenia: An examination between representation activation and maintenance.

BACKGROUND: Anticipatory anhedonia is one of the key deficits found in patients with schizophrenia (SCZ). However, the underlying mechanism of this deficit remains unclear. The present study examined whether representation activation and maintenance capacity influenced anticipatory experiences in SCZ patients. METHODS: We recruited 46 SCZ patients (26 males) and 45 matched healthy controls (24 males). The Reward Representation Activation and Maintenance (RRAM) Task was administrated to assess anticipatory experience and representation activation and maintenance capacity. RESULTS: SCZ patients exhibited lower subjective arousal than controls in anticipation of rewards with high probability when representation activation and maintenance were difficult to accomplish. SCZ patients also tended to reduce their button presses more than HC when they were required to maintain reward representation. CONCLUSIONS: Our findings suggest that representation activation and maintenance may partially account for anticipatory anhedonia observed in SCZ patients.

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.

Clinical utility of the dual n-back task in schizophrenia: A functional imaging approach.

The neural correlate of working memory (WM) impairment in schizophrenia is key to the understanding of the cognitive deficits observed in this disorder. We sought to determine the clinical validity of the dual version n-back paradigm in patients with schizophrenia, and whether schizophrenia patients exhibit altered brain activation patterns compared with healthy controls in this dual version WM measure using functional magnetic resonance imaging. Patients with schizophrenia (n = 20) and healthy controls (n = 24) performed the dual n-back task that consists of both visuospatial and auditory-verbal n-back streams, in which participants were required to monitor and update the contents from these two different inputs simultaneously. Significant positive correlations were found between performance in the dual 2-back condition and another measure of WM capacity and IQ estimates. Moreover, hypoactivation was observed at the right middle frontal gyrus and the posterior parietal regions in schizophrenia participants compared with healthy controls. The right hippocampus was less deactivated in schizophrenia patients compared with healthy controls. Our results support the clinical utility of the dual n-back task in schizophrenia and may have implications for the development of specific cognitive training targeting these impaired neural substrates in relation to WM in patients with schizophrenia.

Striatal dysfunction in patients with schizophrenia and their unaffected first-degree relatives.

Despite empirical findings showing that patients with schizophrenia and their unaffected first-degree relatives have deficits in processing monetary incentives, it is unclear whether similar deficits could be demonstrated for affective incentives. Twenty-six patients with schizophrenia and 26 age and gender matched healthy controls; 23 unaffected first-degree relatives and 23 matched healthy controls were recruited to complete a Monetary Incentive Delay (MID) task and an Affective Incentive Delay (AID) task in a 3-Tesla MRI scanner. Hypoactivation in the dorsal striatum when anticipating monetary incentives were found in patients with schizophrenia and their unaffected first-degree relatives compared with healthy controls. Furthermore, patients with schizophrenia showed hyperactivation in the ventral striatum when receiving both monetary and affective incentives. These findings suggest that disorganized striatal function, regardless of incentive types, may be present in patients with schizophrenia and before the onset of illness in their first-degree unaffected relatives.

Pleasure Experience and Emotion Expression in Patients with Schizophrenia.

BACKGROUND: Impairments in emotional experience and expression have been observed in patients with schizophrenia. However, most previous studies have been limited to either emotional experience (especially anhedonia) or expression. Few studies have examined both the experience and expression of emotion in schizophrenia patients at the same time. AIMS: The present study aimed to examine pleasure experience and emotion expression in patients with schizophrenia. In particular, we specifically examined the relationship between emotion impairments (both pleasure experience and expression) and negative symptoms. METHODS: One hundred and fifty patients completed the Temporal Experience of Pleasure Scale and Emotional Expressivity Scale. RESULTS: Schizophrenia patients exhibited deficits in experiencing pleasure, but showed intact reported emotion expression. Patients with prominent negative symptoms showed reduced anticipatory pleasure, especially in abstract anticipatory pleasure. CONCLUSION: The present findings suggest that patients with schizophrenia have deficits in pleasure experience, while their abilities to express emotion appear intact. Such deficits are more severe in patients with prominent negative symptoms.