Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study.

BACKGROUND: Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown. METHODS: Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group. RESULTS: We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a 'cortico-subcortical-cortical' network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls. CONCLUSIONS: Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Hub-connected functional connectivity within social brain network weakens the association with real-life social network in schizophrenia patients.

Hubs in the brain network are the regions with high centrality and are crucial in the network communication and information integration. Patients with schizophrenia (SCZ) exhibit wide range of abnormality in the hub regions and their connected functional connectivity (FC) at the whole-brain network level. Study of the hubs in the brain networks supporting complex social behavior (social brain network, SBN) would contribute to understand the social dysfunction in patients with SCZ. Forty-nine patients with SCZ and 27 healthy controls (HC) were recruited to undertake the resting-state magnetic resonance imaging scanning and completed a social network (SN) questionnaire. The resting-state SBN was constructed based on the automatic analysis results from the NeuroSynth. Our results showed that the left temporal lobe was the only hub of SBN, and its connected FCs strength was higher than the remaining FCs in both two groups. SCZ patients showed the lower association between the hub-connected FCs (compared to the FCs not connected to the hub regions) with the real-life SN characteristics. These results were replicated in another independent sample (30 SCZ and 28 HC). These preliminary findings suggested that the hub-connected FCs of SBN in SCZ patients exhibit the abnormality in predicting real-life SN characteristics.

Altered empathy-related resting-state functional connectivity in patients with bipolar disorder.

Empathy is the ability to generate emotional responses (i.e., cognitive empathy) and to make cognitive inferences (i.e., affective empathy) to other people's emotions. Empirical evidence suggests that patients with bipolar disorder (BD) exhibit impairment in cognitive empathy, but findings on affective empathy are inconsistent. Few studies have examined the neural mechanisms of cognitive and affective empathy in patients with BD. In this study, we examined the empathy-related resting-state functional connectivity (rsFC) in BD patients. Thirty-seven patients with BD and 42 healthy controls completed the self-report Questionnaires of Cognitive and Affective Empathy (QCAE), the Yoni behavioural task, and resting-sate fMRI brain scans. Group comparison of empathic ability was conducted. The interactions between group and empathic ability on seed-based whole brain rsFC were examined. BD patients scored lower on the Online Simulation subscale of the QCAE and showed positive correlations between cognitive empathy and the rsFC of the dorsal Medial Prefrontal Cortex (dmPFC) with the lingual gyrus. The correlations between cognitive empathy and the rsFC of the temporal-parietal junction (TPJ) with the fusiform gyrus, the cerebellum and the parahippocampus were weaker in BD patients than that in healthy controls. These findings highlight the underlying neural mechanisms of empathy impairments in BD patients.

The diagnostic threshold of Cornell assessment of pediatric delirium in detection of postoperative delirium in pediatric surgical patients.

BACKGROUND: Cornell assessment of pediatric delirium (CAPD) showed advantage in diagnosis of pediatric delirium in Chinese critically ill patients. But its performance in surgical patients is still unclear. The present study was designed to validate the diagnostic performance of CAPD in surgical pediatric patients. METHODS: This is a prospective validation study. Pediatric patients who underwent selective surgery and general anesthesia were enrolled. Primary outcome was the incidence of delirium within postoperative three days. CAPD Chinese version was used to evaluate if the patient had delirium one time per day. At the meantime, a psychiatrist employed Diagnostic and Statistical Manual of Mental Disorders fifth edition to diagnose delirium, which was the "gold standard", and the result was considered as reference standard. Sensitivity, specificity and area under receiver operating characteristic (ROC) curve were calculated to investigate the performance of CAPD. RESULTS: A total of 170 patients were enrolled. Median age was 4 years old. As diagnosed by psychiatrist, 23 (13.5 %) patients experienced at least one episode of delirium during the follow-up period. When diagnostic threshold was set at 9, CAPD showed the optimal sensitivity (87.0 %, 95 %CI 65.3 %-96.6 %) and specificity (98.0 %, 95 %CI 93.7 %-99.5 %) in comparison with other diagnostic thresholds. ROC analysis showed that CAPD was a good delirium assessment instrument with area under curve of 0.911 (95 % CI 0.812 to 1.000, P < 0.001). Agreement between CAPD and reference standard was 0.849 (Kappa coefficient, P < 0.001). CONCLUSIONS: This study found that Cornell assessment of pediatric delirium could be used as an effective instrument in diagnosis of delirium in pediatric surgical patients. TRIAL REGISTRATION: www.chictr.org.cn Identifier: ChiCTR-DDD-17,012,231, August 3, 2017.

Cross-cultural adaptation and validation of the 3D-CAM Chinese version in surgical ICU patients.

BACKGROUND: Accurate diagnosis of delirium is very important for prevention and treatment. Present study was designed to validate the 3-Minute Diagnostic Interview for CAM-defined Delirium Chinese version (3D-CAM-CN) in surgical ICU patients. METHODS: In this prospective diagnostic study, the 3D-CAM was translated into Chinese with culture adaption. Two interviewers (Roles A and B) independently administrated 3D-CAM-CN assessment in adult patients from postoperative days 1 to day 3. At the meantime, a panel of psychiatrists diagnosed delirium according to the Diagnostic and Statistical Manual of Mental Disorders-fifth edition as the reference standard. The sensitivity and specificity were calculated to analyze the diagnostic character of the 3D-CAM-CN. Kappa coefficient was used to evaluate interrater reliability. RESULTS: Two hundred forty-five adult patients were assessed for at least 2 days, resulting a total of 647 paired-assessments. When compared with the reference standard, the sensitivity and specificity of the 3D-CAM-CN assessment were 87.2 and 96.7%, respectively, by Role A and 84.6 and 97.4%, respectively, by Role B, with good interrater reliability (Kappa coefficient = 0.82, P < 0.001). It also performed well in patients with mild cognitive impairment, with the sensitivity from 85.7 to 100% and the specificity from 95.7 to 96.4%. CONCLUSION: Our results showed that the 3D-CAM-CN can be used as a reliable and accurate instrument for delirium assessment in surgical patients. TRIAL REGISTRATION: This trail was approved by the Clinical Research Ethic Committee of Peking University First Hospital (No. 2017-1321) and registered on Chinese clinical trial registry on July 6, 2017 (ChiCTR-OOC-17011887).

Validation of the Questionnaire of Cognitive and Affective Empathy in patients with schizophrenia, major depressive disorder and bipolar disorder.

INTRODUCTION: Alteration of empathy is common in patients with psychiatric disorders. Reliable and valid assessment tools for measuring empathy of clinical samples is needed. The Questionnaire of Cognitive and Affective Empathy (QCAE) is a newly-developed instrument to capture cognitive and affective components of empathy. This study aimed to validate the QCAE and compared self-reported empathy between clinical groups with varied psychiatric diagnoses and healthy sample. METHODS: The present study performed factor analysis for the QCAE on clinical samples in the Chinese setting (n = 534), including patients with schizophrenia (n = 158), bipolar disorder (n = 213) and major depressive disorder (n = 163). Internal consistency, internal correlation and convergent validity was examined in the subsample (n = 361). Group comparison among patients with schizophrenia, bipolar disorder, major depressive disorder and healthy controls (n = 107) was conducted to assess the discriminant validity. RESULTS: Our results indicated acceptable factor model, good reliability and validity of the QCAE. Impaired cognitive empathy was found in clinical samples, especially in patients with schizophrenia, while higher affective empathy was found in patients with bipolar disorder and major depressive disorder. CONCLUSION: The QCAE is a useful tool in assessing empathy in patients with varied psychiatric diagnoses.

Social brain network correlates with real-life social network in individuals with schizophrenia and social anhedonia.

Social behaviour requires the brain to efficiently integrate multiple social processes, but it is not clear what neural substrates underlie general social behaviour. While psychosis patients and individuals with subclinical symptoms are characterized by social dysfunction, the neural mechanisms underlying social dysfunctions in schizophrenia spectrum disorders remains unclear. We first constructed a general social brain network (SBN) using resting-state functional connectivity (FC) with regions of interest based on the automatic meta-analysis results from NeuroSynth. We then examined the general SBN and its relationship with social network (SN) characteristics in 30 individuals with schizophrenia (SCZ) and 33 individuals with social anhedonia (SA). We found that patients with SCZ exhibited deficits in their SN, while SA individuals did not. SCZ patients showed decreased segregation and functional connectivity in their SBN, while SA individuals showed a reversed pattern with increased segregation and functional connectivity of their SBN. Sparse canonical correlation analysis showed that both SCZ patients and SA individuals exhibited reduced correlation between SBN and SN characteristics compared with their corresponding healthy control groups. These preliminary findings suggest that both SCZ and SA participants exhibit abnormality in segregation and functional connectivity within the general SBN and reduced correlation with SN characteristics. These findings could guide the development of non-pharmacological interventions for social dysfunction in SCZ spectrum disorders.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial.

BACKGROUND: Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. AIMS: The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). METHODS: This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. RESULTS: 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. CONCLUSION: BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression.