Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study.

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study.

BACKGROUND: Ziprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia. METHODS: A total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10-40 mg daily and started sequentially with oral ziprasidone 40-80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120-160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment. RESULTS: Out of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2-Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported. CONCLUSIONS: Ziprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients. TRIAL REGISTRATION: The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn : ChiCTR-OIC-16007970.

Prevalence of Heavy Menstrual Bleeding and Its Associated Cognitive Risks and Predictive Factors in Women With Severe Mental Disorders.

There has been limited studies examining treatment-induced heavy menstrual bleeding (HMB) in women with severe mental illnesses. The aim of this study was to examine HMB prevalence and HMB-associated factors in young women (18-34 years old) diagnosed with bipolar disorder (BP), major depressive disorder (MDD), or schizophrenia (SCZ) who have full insight and normal intelligence. Eighteen-month menstruation histories were recorded with pictorial blood loss assessment chart assessments of HMB. Multivariate analyses were conducted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Drug effects on cognition were assessed with the MATRICS Consensus Cognitive Battery (MCCB). HMB prevalence were: BP, 25.85%; MDD, 18.78%; and SCH, 13.7%. High glycosylated hemoglobin (HbA1c) level was a strong risk factor for HMB [BP OR, 19.39 (16.60-23.01); MDD OR, 2.69 (4.59-13.78); and SCZ OR, 9.59 (6.14-12.43)]. Additional risk factors included fasting blood sugar, 2-h postprandial blood glucose, and use of the medication valproate [BP: OR, 16.00 (95%CI 12.74-20.22); MDD: OR, 13.88 (95%CI 11.24-17.03); and SCZ OR, 11.35 (95%CI 8.84-19.20)]. Antipsychotic, antidepressant, and electroconvulsive therapy use were minor risk factors. Pharmacotherapy-induced visual learning impairment was associated with HMB [BP: OR, 9.01 (95%CI 3.15-13.44); MDD: OR, 5.99 (95%CI 3.11-9.00); and SCZ: OR, 7.09 (95%CI 2.99-9.20)]. Lithium emerged as a protective factor against HMB [BP: OR, 0.22 (95%CI 0.14-0.40); MDD: OR, 0.30 (95%CI 0.20-0.62); and SCZ: OR, 0.65 (95%CI 0.33-0.90)]. In SCZ patients, hyperlipidemia and high total cholesterol were HMB-associated factors (ORs, 1.87-2.22). Psychiatrist awareness of HMB risk is concerningly low (12/257, 2.28%). In conclusion, prescription of VPA should be cautioned for women with mental illness, especially BP, and lithium may be protective against HMB.

Prescription practices in the treatment of agitation in newly hospitalized Chinese schizophrenia patients: data from a non-interventional naturalistic study.

BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.

What is the optimal neuropsychological test battery for schizophrenia in China?

BACKGROUND: The MATRICS consensus cognitive battery (MCCB) has been widely used to evaluate cognitive deficits in schizophrenia (SCZ), however, no study has formally examined the validity of the MCCB in Chinese SCZ. This study compared Chinese SCZ patients with healthy Chinese controls on the MCCB and some additional neurocognitive tests to determine if the Chinese MCCB is an optimal battery to assess the cognitive deficits in Chinese SCZ patients. METHOD: The study enrolled and examined 230 patients met DSM-IV criteria for SCZ and 656 healthy controls matched for gender, age and education. Besides the MCCB, we also included some additional neurocognitive tests that have been widely used in patients with schizophrenia. We selected MCCB and non-MCCB tests with large effect size, to assemble a new "optimal battery" and compared its performance with that of the standard MCCB. RESULTS: Comparing the putative "optimal" battery with the original MCCB, more patients with SCZ were identified as cognitively impaired according to the criteria of GDS ≥ 0.50 for the optimal battery (166 vs 135, or 72.2% vs 58.7%). The rate of cognitive impairment according to MCCB GDS in patients with SCZ who were currently working, ever worked and never worked are 45.5%, 61.6% and 70.8% (p = 0.051), whereas the optimal battery GDS showed 56.4%, 74.8%, 91.7% (p = 0.003), respectively. CONCLUSIONS: Our study needs validation with independent samples but suggests that the current "optimal" cognitive battery could be more sensitive than the widely used MCCB in detecting SCZ related cognitive impairment in China.

Dysfunction of Pre-Attentive Visual Information Processing in Drug-Naïve Women, But Not Men, During the Initial Episode of Major Depressive Disorder.

Women are twice as likely as men to develop depression. Few studies have explored gender difference in cognitive function of patients with MDD. The gender difference in the pre-attentive information processing of MDD patients is still poorly understood. To examine the gender differences in change detection, 30 medication-free MDD patients (15 women) and 30 age and education matched controls (15 women) were recruited. The deviant-standard reverse oddball paradigm (50 ms/150 ms) was used to obtain the visual mismatch negativity (vMMN) in first episode MDD patients. Compared to men with MDD, women with MDD showed a significantly decreased increment vMMN, while no gender difference in decrement vMMN was found. The increment vMMN amplitude in MDD women was smaller than in healthy women, whereas no difference was found in decrement vMMN. Neither increment nor decrement vMMN differed between MDD men and healthy men. The mean amplitude of increment vMMN was not correlated with symptoms of MDD in MDD patients and MDD women. To conclude, the dysfunction of visual information processing existed at pre-attentive stage in MDD women.

Literature review and economic evaluation of oral and intramuscular ziprasidone treatment among patients with schizophrenia in China.

BACKGROUND: Over 10 million Chinese are affected by schizophrenia. The annual cost of schizophrenia in China was estimated at US$2586 per patient. AIMS: The study has two aims: (1) to conduct a targeted literature review of the economic literature on oral ziprasidone in China, and (2) to develop an inpatient economic model that compared the cost of intramuscular ziprasidone with other regimens including electroconvulsive therapy (ECT) for the management of acute agitation in patients with schizophrenia from a hospital's perspective in China. METHODS: A targeted literature review was conducted using PubMed and the Chinese literature databases for studies published between January 2007 and December 2017. Studies that assessed costs associated with oral ziprasidone treatment for schizophrenia in China were summarised. In the inpatient economic model, cost measures included hospital room and board, antipsychotics, ECT and medications for the management of extrapyramidal symptoms (EPS). Input for standard antipsychotic regimens and unit cost were obtained from the literature. Hospital length of stay (LOS), utilisation of ECT and incidence of EPS were derived from the literature and supplemented/validated with a survey of psychiatrists in China. Cost was presented in 2017 Chinese yuan. RESULTS: The average estimated LOS was 29 days with ziprasidone, 33 days with risperidone+benzodiazepine, 32 days with olanzapine, 35 days with haloperidol and 29 days with ECT. The cost of antipsychotics was ¥1260 with ziprasidone, ¥137 with risperidone+benzodiazepine, ¥913 with olanzapine and ¥210 with haloperidol; ECT treatment cost ¥785. The base-case analysis suggested that higher antipsychotic cost with ziprasidone was offset by savings with shorter LOS. Using intramuscular ziprasidone for acute management was associated with a total cost of ¥11 157, the lowest among all antipsychotic regimens (¥11 424 with risperidone+benzodiazepine, ¥11 711 with olanzapine and ¥11 912 with haloperidol) and slightly higher than ECT (¥10 606). The cost of antipsychotics and ECT accounted for 1 %-11 % of the total cost. Varying LOS between the lower and upper bounds of the 95% CI, the total cost was comparable between these regimens. CONCLUSIONS: Overall, the cost for the management of acute agitation was similar between intramuscular ziprasidone and other antipsychotics. Compared with other antipsychotics, the higher medication cost of intramuscular ziprasidone can be offset by savings with shorter hospital stay. The results from this economic analysis were complementary to the findings in the published literature assessing the economic outcomes of oral ziprasidone.

Prevalence and risk factors of agitation in newly hospitalized schizophrenia patients in China: An observational survey.

This multi-center observational study investigated the prevalence of agitation in newly hospitalized schizophrenia patients in China and its potential risk factors. It was performed in 2014 and covered 14 hospitals. Newly hospitalized patients with schizophrenia or suspected schizophrenia who met the diagnostic criteria of the International Statistical Classification of Diseases and Related Health Problems, 10th revision, were recruited. Agitation and related risk factors were evaluated by a questionnaire designed for the survey. General demographic data, disease characteristics, scores on schizophrenia rating scales and agitation rating scales (e.g., Positive and Negative Syndrome Scale-Excited Component [PANSS-EC] and Behavioral Activity Rating Scale [BARS]) were collected. Among the 1512 patients screened in the study, 1400 (92.59%) were eligible. According to the PANSS-EC and BARS, the prevalence of agitation was 60.92% (853 of 1400) and 59.00% (826 of 1400), respectively. The overall prevalence of agitation was 47.50% (665 of 1400). The most important risk factor of agitation was being aggressive at baseline (Modified Overt Aggression Scale score ≥4, odds ratio=6.54; 95% confidence interval=4.93-8.69). Other risk factors included a history of aggressive behavior, northern region of residence, involuntary hospitalization, disease severity, low level of education, living alone, being unemployed or retired.

Interactions between the vascular endothelial growth factor gene polymorphism and life events in susceptibility to major depressive disorder in a Chinese population.

BACKGROUND: Recent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). METHODS: DNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). RESULTS: Differences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. CONCLUSIONS: These results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8-week, prospective, open-label, multicenter, single-arm study.

INTRODUCTION: This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. METHODS: A multicenter, single-arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. RESULTS: A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. DISCUSSION: Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia.

Gender differences in pre-attentive change detection for visual but not auditory stimuli.

OBJECTIVE: Despite ongoing debate about gender differences in pre-attention processes, little is known about gender effects on change detection for auditory and visual stimuli. We explored gender differences in change detection while processing duration information in auditory and visual modalities. METHOD: We investigated pre-attentive processing of duration information using a deviant-standard reverse oddball paradigm (50 ms/150 ms) for auditory and visual mismatch negativity (aMMN and vMMN) in males and females (n=21/group). RESULT: In the auditory modality, decrement and increment aMMN were observed at 150-250 ms after the stimulus onset, and there was no significant gender effect on MMN amplitudes in temporal or fronto-central areas. In contrast, in the visual modality, only increment vMMN was observed at 180-260 ms after the onset of stimulus, and it was higher in males than in females. CONCLUSION: No gender effect was found in change detection for auditory stimuli, but change detection was facilitated for visual stimuli in males. SIGNIFICANCE: Gender effects should be considered in clinical studies of pre-attention for visual stimuli.

The MATRICS Consensus Cognitive Battery (MCCB): Co-norming and standardization in China.

MATRICS Consensus Cognitive Battery (MCCB), packaging 10 tests selected from more than 90 nominated tests, is a method developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) group to evaluate the efficacy of treatments targeting cognitive impairments in schizophrenia. MCCB had been translated into a number of languages, but only the US and Spain had normative data reported. Inconsistency in translation and cultural differences make direct application of MCCB in China problematic. In this study, we administered the battery to a representative community sample based on Chinese population census in 2005 and obtained normative data. The effects of age, gender, education level, and scale of residence area on test performance were examined. The sample included 656 healthy volunteers from six sites in China. At each site, sample was stratified according to age, gender, and educational level, and scale of the area one was born in, grew up in and currently living in was recorded. We found age, gender, and education had significant effects on the normative data for MCCB in China, which are comparable to those found for the original standardized English version in the U.S. and the Spanish version in Spain. Remarkably, the residence scale effects on neuropsychological performance were significant, which should be taking into account when calculating the standardized T score for each subject. The practice effects were minor and test-retest reliability of MCCB was good, which suggests MCCB as an appropriate measure for clinical and research usage in China.

Gender effect on pre-attentive change detection in major depressive disorder patients revealed by auditory MMN.

Gender differences in rates of major depressive disorder (MDD) are well established, but gender differences in cognitive function have been little studied. Auditory mismatch negativity (MMN) was used to investigate gender differences in pre-attentive information processing in first episode MDD. In the deviant-standard reverse oddball paradigm, duration auditory MMN was obtained in 30 patients (15 males) and 30 age-/education-matched controls. Over frontal-central areas, mean amplitude of increment MMN (to a 150-ms deviant tone) was smaller in female than male patients; there was no sex difference in decrement MMN (to a 50-ms deviant tone). Neither increment nor decrement MMN differed between female and male patients over temporal areas. Frontal-central MMN and temporal MMN did not differ between male and female controls in any condition. Over frontal-central areas, mean amplitude of increment MMN was smaller in female patients than female controls; there was no difference in decrement MMN. Neither increment nor decrement MMN differed between female patients and female controls over temporal areas. Frontal-central MMN and temporal MMN did not differ between male patients and male controls. Mean amplitude of increment MMN in female patients did not correlate with symptoms, suggesting this sex-specific deficit is a trait- not a state-dependent phenomenon.

Impaired pre-attentive change detection in major depressive disorder patients revealed by auditory mismatch negativity.

Patients with major depressive disorder (MDD) show deficits in cognitive functions. However, the neural mechanisms underlying the pre-attentive information processing in MDD patients are poorly understood. The present study investigated whether MDD patients have impairments in pre-attentive information processing indexed by auditory mismatch negativity (MMN). The deviant-standard reverse oddball paradigm was used to obtain the memory-comparison-based duration auditory MMN in 24 MDD patients and 24 healthy control subjects. Over the frontal-central area, MDD patients exhibited decreased MMN amplitudes only for the increment condition (150-ms MMN), whereas the temporal MMN did not differ between MDD patients and healthy subjects, regardless of the increment or decrement (50-ms MMN) condition. The MMN amplitudes were not correlated with depression symptoms. In addition, the peak latency of MMN amplitudes was longer in the MDD patients than the control subjects. These data indicate that pre-attentive information processing is impaired in MDD patients. This dysfunction may represent a trait of MDD patients rather than a state-dependent phenomenon.

Association between painful physical symptoms and clinical outcomes in Chinese patients with major depressive disorder: a three-month observational study.

BACKGROUND: Painful physical symptoms (PPS) may present as a component of major depressive disorder (MDD). Their effect in Chinese patients has not been investigated. This analysis reports the changes in disease severity, treatment patterns, quality of life and outcomes in a Chinese cohort according to the presence (PPS+) or absence (PPS-) of painful physical symptoms. METHODS: A subgroup of Chinese patients from a large observational 3-month study of patients from Asian countries and regions of China were classified using the modified Somatic Symptom Inventory (SSI) as PPS+ (mean score >or= 2) or PPS- (mean score < 2). Depression severity was assessed with the Clinical Global Impression of Severity (CGI-S) scale and 17-item Hamilton depression rating scale (HAMD(17)). Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well-being. Antidepressants were compared with regard to their efficacy. RESULTS: Of the 299 Chinese patients enrolled in the study, 105 were classified as PPS+ (73/105, 70% women). At baseline, PPS+ patients reported greater pain severity (VAS, mean (SD): 49.56 (26.49) vs. 16.60 (20.99) for PPS-, P < 0.01), were more depressed (HAMD(17), mean (SD): 25.32 (5.47) vs. 23.33 (5.24) for PPS-, P = 0.002) and had poorer quality of life (EQ-5D Health State, mean (SD): 38.48 (22.38) vs. 49.57 (18.54) for PPS-, P < 0.001). PPS+ patients showed less overall improvement in depressive symptom severity (HAMD(17), change from baseline (95%CI): -17.38 (-18.65, -16.12) vs. -19.20 (-20.05, -18.35) for PPS-, P = 0.032; CGI-S, change from baseline (95%CI): -2.85 (-3.11, -2.58) vs. -3.20 (-3.38, -3.02) for PPS-, P = 0.044). CONCLUSIONS: PPS were less frequent than expected compared with previous studies of Asian populations. PPS+ were associated with greater MDD severity and less improvement than PPS- when antidepressants were given.