Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.

A comparison of clinical characteristics of psychiatric inpatients in three hospitals from Western China and America.

BACKGROUND: Different countries have differences in social and cultural context and health system, which may affect the clinical characteristics of psychiatric inpatients. This study was the first to compare cross-cultural differences in the clinical characteristics of psychiatric inpatients in three hospitals from Western China and America. METHODS: Overall, 905 and 1318 patients from three hospitals, one in America and two in Western China, respectively, were included. We used a standardised protocol and data collection procedure to record inpatients' sociodemographic and clinical characteristics. RESULTS: Significant differences were found between hospitals from the two countries. Positive symptoms were the main reason for admission in the Chinese hospitals, while reported suicide and self-injury symptoms more frequently led to hospital admission in America. Moreover, there were more inpatients with combined substance abuse in the American hospital (97.6% vs. 1.9%, P < 0.001). The length of stay (LOS) in America was generally shorter than in China (10.5 ± 11.9 vs. 20.7 ± 13.4, P < 0.001). The dosage of antipsychotic drugs used in the American hospital was higher than in China (275.1 ± 306.9 mg vs. 238.3 ± 212.5 mg, P = 0.002). Regression analysis showed that male sex, older age, retirees, being admitted because of physical symptoms, and using higher doses of antipsychotic drugs were significantly associated with longer hospitalisation in the American hospital (P < 0.05). Comparatively, patients who were divorced, experiencing suicidal ideation, admitted involuntarily, admitted because of physical, depression, or anxiety symptoms, and using higher doses of antipsychotic drugs had longer hospitalisation in Chinese hospitals (P < 0.05). CONCLUSION: Significant variations in clinical characteristics of inpatients were found between hospitals from Western China and America. The LOS in Chinese hospitals was significantly longer, but patients used higher doses of antipsychotic drugs in the American hospital. Admission due to physical symptoms and the use of higher dosage drugs were related to longer LOS in both countries.

Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial.

BACKGROUND: This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. METHODS: This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18-60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. RESULTS: A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. CONCLUSIONS: After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

Association between residual symptoms and social functioning in patients with depression.

OBJECTIVE: There is a lack of data about residual symptoms in Chinese patients with depression. The aim of this study was to evaluate the association of residual symptoms with social functional impairment in these patients. METHODS: This was a multicenter cross-sectional study conducted in 11 hospitals in eight cities of China from September 2014 to April 2015. Residual symptoms and social functioning were assessed using the SDS, QIDS-SR16, Q-LES-Q-SF, and PHQ-15 scales. Logistic regression analysis was used to determine the factors associated with social functional impairment. RESULTS: Among the 1503 patients, 915 (60.9%) had no functional impairment (SDS ≤6) and 588 (39.1%) showed functional impairment (SDS >6). Those with impairment had higher PHQ-15 scores (7.4 ± 4.8 vs. 4.0 ± 3.4, P < 0.0001), lower Q-LES-Q-SF scores (all items P < 0.0001), higher SDS scores (13.9 ± 5.7 vs. 2.8 ± 2.2, P < 0.0001), and higher scores for all QIDS dimensions (all P < .0001). The factors related to functional impairment included QIDS dimension 7 (loss of interest) (OR = 2.137, 95%CI 1.600-2.853, P < 0.0001), QIDS dimension 9 (mental anxiety) (OR = 1.627, 95%CI 1.215-2.180, P = 0.0011), QIDS dimension 3 (appetite) (OR = 1.502, 95%CI 1.141-1.977, P = 0.0037), QIDS dimension 8 (energy) (OR = 1.468, 95%CI 1.092-1.973, P = 0.0110), age (OR = 0.982, 95%CI 0.971-0.993, P = 0.0013), disease course (OR = -1.004, 95%CI 1.002-1.006, P = 0.0004), and QIDS dimension 1 (sleep disorders) (OR = 1.622, 95%CI 1.068-2.463, P = 0.0232). CONCLUSION: Compared with patients with normal social function, cases with impaired social function have more physical symptoms, more residual symptoms of depression, and less satisfaction with the quality of life. Residual symptoms are associated with social functional impairment in patients with depression.

Potential prognostic value of clinical characteristics, hormone status and major depressive disorder in breast cancer.

AIM: To identify independent factors predicting overall survival (OS) of breast cancer (BC) patients. PATIENTS & METHODS: Two hundred and eighty one women with BC were recruited and clinical characteristics including lymphovascular invasion, clinical stage of Tumor Node Metastasis and positive axillary lymph nodes were documented; immunohistochemistry/fluorescence in situ hybridization was used to examine the expression of estrogen receptor, progesterone receptor, HER2 and Ki-67; major depressive disorder was assessed with Diagnostic and Statistical Manual of Mental Disorders V. RESULTS: Multivariable analyses indicated that in BC patients, lymphovascular invasion, Tumor Node Metastasis, pN, Ki-67 and major depressive disorder were significantly negatively correlated with OS; estrogen receptor was significantly positively associated with OS. CONCLUSION: Early diagnostic approaches and effective psychologic intervention are indispensable for BC patients.

Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

Intramuscular ziprasidone versus haloperidol for managing agitation in Chinese patients with schizophrenia.

Intramuscular (IM) antipsychotics are preferred for efficient control of agitation symptoms. Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia. However, clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability. This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia. Subjects with acute schizophrenia were randomized to either ziprasidone (n = 189, 10 to 20 mg as required up to a maximum of 40 mg/d) or haloperidol (n = 187, 5 mg every 4 to 8 hours to a maximum of 20 mg/d) for 3 days. Psychiatric assessments and adverse events were assessed at baseline, 2, 4, 24, 48, and 72 hours. In the ziprasidone group, 2.1% of subjects discontinued versus 3.7% in the haloperidol group. The least squares mean change (SE) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was -17.32 (0.7) for ziprasidone (n = 167) and -18.44 (0.7) for haloperidol (n = 152), with a 95% confidence interval treatment difference of -0.7 to 2.9. Fewer subjects experienced adverse events after ziprasidone (n = 54, 28.6%) than haloperidol (n = 116, 62.0%), with a notably higher incidence of extrapyramidal symptoms in the haloperidol group (n = 69, 36.9%) compared to the ziprasidone group (n = 4, 2.1%). For controlling agitation in schizophrenia in this Chinese study, ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol.

[Influence of coping style and social support on quality of life in patients with impaired glucose tolerance].

OBJECTIVE: To explore how coping style and social support influence the quality of life in patients with impaired glucose tolerance, which act respectively as the internal and external mediating ways. METHODS: A total of 283 patients with impaired glucose tolerance from 6 Three-A hospitals in China were surveyed with self-rating anxiety scale, self-rating depression scale, trait coping style questionnaire, social support scale, and WHOQOL-BREF. RESULTS: Biographic data failed to predict the quality of life in patients with impaired glucose tolerance, while anxiety, depression, social support and coping style significantly influenced their quality of life. CONCLUSION: The fact that emotional disorder, social support and coping style influence the quality of life in patients with type 2 diabetes also exists in patients with impaired glucose tolerance.

Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese.

The phosphodiesterase 4B (PDE4B) is a candidate susceptibility gene for schizophrenia (SCZ), interacting with DISC1, a known genetic risk factor for SCZ. To examine if variants within PDE4B gene are associated with SCZ in Northwestern Han Chinese, and if these effects vary in gender-specific subgroup, we analyzed 20 SNPs, selected from previous studies and preliminary HapMap data analyses with minor allele frequency (MAF) ≥ 20%, in a cohort of 428 cases and 572 controls from genetically independent Northwestern Han Chinese. Single SNP association, haplotype association and sex-specific association analysis were performed. We found that rs472952 is significantly associated with SCZ and rs7537440 is associated with SCZ in females. Further analysis indicated that a haplotype block spanning PDE4B2 splice site is highly associated with SCZ and several haplotypes in this block have about twofold to threefold increase in cases. Our results provide further evidence that PDE4B may play important roles in the etiology of SCZ.

Stressful events induce long-term gut microbiota dysbiosis and associated post-traumatic stress symptoms in healthcare workers fighting against COVID-19.

OBJECTIVE: The microbiota-gut-brain axis is a key pathway perturbed by prolonged stressors to produce brain and behavioral disorders. Frontline healthcare workers (FHWs) fighting against COVID-19 typically experience stressful event sequences and manifest some mental symptoms; however, the role of gut microbiota in such stress-induced mental problems remains unclear. We investigated the association between the psychological stress of FHW and gut microbiota. METHODS: We used full-length 16S rRNA gene sequencing to characterize the longitudinal changes in gut microbiota and investigated the impact of microbial changes on FHWs' mental status. RESULTS: Stressful events induced significant depression, anxiety, and stress in FHWs and disrupted the gut microbiome; gut dysbiosis persisted for at least half a year. Different microbes followed discrete trajectories during the half-year of follow-up. Microbes associated with mental health were mainly Faecalibacterium spp. and [Eubacterium] eligens group spp. with anti-inflammatory effects. Of note, the prediction model indicated that low abundance of [Eubacterium] hallii group uncultured bacterium and high abundance of Bacteroides eggerthii at Day 0 (immediately after the two-month frontline work) were significant determinants of the reappearance of post-traumatic stress symptoms in FHWs. LIMITATIONS: The lack of metabolomic evidence and animal experiments result in the unclear mechanism of gut dysbiosis-related stress symptoms. CONCLUSION: The stressful event sequences of fighting against COVID-19 induce characteristic longitudinal changes in gut microbiota, which underlies dynamic mental state changes.

Is the EFNB2 locus associated with schizophrenia? Single nucleotide polymorphisms and haplotypes analysis.

Recently, evidence of linkage of schizophrenia to chromosome 13q22-q34 has been demonstrated in multiple studies. Based on structure and function, EFNB2 may be considered as a compelling candidate gene for schizophrenia on chromosome 13q33. We genotyped three single-nucleotide polymorphisms (SNPs: rs9520087, rs11069646, and rs8000078) in this region in 846 Han Chinese subjects (477 cases and 369 controls). Significant association between an allele of marker rs9520087 and schizophrenia was found. Furthermore, since no LD was observed in the three SNPs linkage disequilibrium estimation, all three SNPs were used in multiple SNPs haplotype analysis, and a strongly significant difference was found for the common haplotype TTC. Overall our findings indicate that EFNB2 gene may be a candidate susceptibility gene for schizophrenia in the Han Chinese population, and also provide further support for the potential importance of the NMDA receptor pathway in the etiology of schizophrenia.

A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression.

AIM: Post-stroke depression (PSD) is one of the most frequent neuropsychiatric disorders associated with stroke characterized by depression. The neuroplasticity hypothesis postulates that loss of brain-derived neurotrophic factor (BDNF) plays a major role in pathophysiology of PSD, and restoration of it may represent a critical mechanism underlying antidepressant efficacy. METHODS: In previous studies, we designed a new fusion gene, HA2TAT-BDNF, and cloned it into adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for the delivery of BDNF to central nervous system (CNS) via nose-brain pathway. In this study, we used it to explore the antidepressant effects on PSD rats through behavioral and various histological methods, and try to find out its specific mechanism. RESULTS: Compared with the control group, the PSD+AAV group showed decreased sucrose consumption percentage in the sucrose preference test (SPT) (P < 0.001) and prolonged immobility in the forced swimming test (FST) (P=0.000). However, the nasal administration of BDNF-HA2TAT/AAV reversed results of these two behavioral tests (P>0.05, P >0.05), showing an adequate antidepressant effect. Compared with the control group, the concentrations of BDNF mRNA and protein in the hippocampus (P< 0.05, P < 0.01) and prefrontal cortex (P < 0.01, P < 0.01) of PSD rats both decreased. Increased BDNF mRNA and protein expression was observed in the prefrontal cortex (P > 0.05, P < 0.05), without notable change in the hippocampus (P < 0.05, P < 0.001) of PSD+BDNF rats. CONCLUSION: These results suggest that BDNF reductions in the prefrontal cortex and hippocampus are associated with the development of post-stroke depression, and that increased levels of BDNF in the prefrontal cortex could be used as a therapeutic target to treat PSD. However, the exact mechanism of BDNF action remains unclear in this regard, hindering the wider application of our method. We expect that our research could facilitate the exploration of pathogenesis and the new treatment method of PSD.

Quality of Life and Its Correlates in Alcohol Use Disorder Patients With and Without Depression in China.

Objective: Alcohol use disorder (AUD) is a serious issue worldwide and frequently co-occurs with depression. However, the quality of life (QOL) of AUD patients with and without depression is not well studied in the Chinese Han population. The aim of this study was to investigate QOL and its correlates in AUD patients with and without depression in China. Methods: Five hundred and fifteen psychiatric patients diagnosed with AUD were recruited. All these patients completed the Beck Depression Inventory (BDI) to assess depression, the Medical Outcome Study 36-Item Short Form Health Survey (SF-36) to evaluate QOL and the Alcohol Use Disorders Identification Test (AUDIT) to measure the severity of drinking. Results: Compared with AUD patients without depression, those with depression had a lower QOL in all eight domains of the SF-36 (all P < 0.001), but were more willing to have alcohol-related treatment (P < 0.05). Negative correlations were noted between (i) the BDI total score and all eight domains of the SF-36 (all P < 0.001); and (ii) between the AUDIT total score and six domains of the SF-36 (all P < 0.05). Conclusions: Depression impairs QOL in patients with AUD in China. Early intervention in comorbid depression to improve QOL is needed.

Prevalence, Demographic, and Clinical Correlates of Comorbid Depressive Symptoms in Chinese Psychiatric Patients With Alcohol Dependence.

BACKGROUND: Depressive symptoms are common among psychiatric patients with alcohol dependence (AD). However, the prevalence and clinical correlates of comorbid depressive symptoms are less well studied in Chinese Han patients. METHODS: In this hospital-based survey, we recruited 378 psychiatric patients diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). All patients completed the Beck Depression Inventory (BDI) to evaluate depressive symptoms and the Alcohol Use Disorders Identification Test (AUDIT) to assess the severity of drinking. RESULTS: Compared to patients without depressive symptoms, 48.9% (185/378) of the patients with comorbid depressive symptoms were younger, had a more unstable marital status, had a higher AUDIT total score, and had a higher adverse consequences subscore (all P < 0.05). Further logistic regression analysis showed that unstable marital status (Odds ratios [OR] = 2.20, 95% confidence interval [CI] 1.21-3.99) and AUDIT total score (OR=1.07, 95% CI 1.03-1.11) were significantly associated with depressive symptoms. CONCLUSIONS: Our findings indicate high comorbidity between AD and depressive symptoms in Chinese psychiatric patients. Moreover, some variables are correlates of comorbid depressive symptoms. Particular attention should be paid to the early detection and intervention for this comorbid condition and its risk factors.

Does early and late life depression differ in residual symptoms, functioning and quality of life among the first-episode major depressive patients.

AIMS & OBJECTIVES: Age differences exist in many aspects in patients with major depressive disorder (MDD). The present study aims to examine the effect of age on treatment outcomes in first-episode MDD. METHODOLOGY: A total of 982 first-episode major depressive patients, who were above 18 years old and admitted in both psychiatric hospitals and units of general hospitals were recruited for the present study. These patients were newly treated and responded to 8-12 weeks of antidepressant treatment. Depressive symptoms, psychosocial functioning and quality of life were measured using standardized instruments. The study population was divided into three age groups: early adult (18-44 years old), middle adult (45-59 years old), and late adult (60-85 years old). RESULTS: Earlier age was associated with greater symptom severity, severer depressive symptoms in hypersomnia, concentration/decision making, negative view of the self, suicide ideation and restlessness, more impaired function, poorer satisfaction in social relationship and economic status, when compared to late adults with MDD (all P < 0.05). In the multivariable analyses, among the other variables, early age remained as an independent correlation of residual depressive severity (middle age vs. early age: OR = 0.631, 95%CI[0.462, 0.862]; old age vs. early age: OR = 0.521, 95%CI[0.348, 0.780]) and functional impairment. Comorbidity of physical illness had a negative contribution to all treatment outcomes. CONCLUSION: In first major depressive episode, early age was strongly associated with depressive severity and functional impairment after responding to antidepressant treatment. Early-life depression may be an indicator of MDD for poor clinical outcomes and high clinical burden.

Metagenome-wide association of gut microbiome features for schizophrenia.

Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

Impaired visual, working, and verbal memory in first-episode, drug-naive patients with major depressive disorder in a Chinese population.

Cognitive impairment has been observed in patients with major depressive disorder (MDD). However, it remains unclear whether the deficits in specific cognitive domains are present in first-episode, drug-naïve patients or medicated patients. In the present study, using the CogState battery (CSB) Chinese language version, we evaluated the visual, working, and verbal memory in first-episode drug-naive patients and medicated patients with MDD in a Chinese population. We measured the cognitive function in first-episode drug-naïve patients (n = 36), medicated MDD patients (n = 71), and age- and sex-matched healthy control subjects (n = 59) in a Chinese population. The CSB composite scores in both first-episode drug-naive patients and medicated patients were significantly poorer than those in the healthy control subjects. The CSB sub-scores, including visual, working, and verbal memory were also significantly poorer in both patient groups than those in the healthy control subjects. In contrast, processing speed, attention/vigilance, executive function, spatial working memory, and social cognition were no different from healthy controls, whereas the executive function was significantly better in the medicated patients than in the healthy control subjects and first-episode drug-naïve patients. These findings suggest an impairment in the visual, working, and verbal memory in first-episode, drug-naive MDD patients in a Chinese population.

Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double-blind, randomized, placebo-controlled study.

Chinese herbal medicines possess the therapeutic potential for mood disorders. This double-blind, randomized, placebo-controlled study was designed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as an adjunct to carbamazepine (CBZ) in patients with bipolar disorders. One hundred and twenty-four bipolar depressed and 111 manic patients were randomized to treatment with CBZ alone, CBZ plus FEWP, or equivalent placebo for 12 weeks. CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day. Efficacy measures included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale, Bech-Rafaelsen Mania Scale, and Clinical Global Impression-Severity (CGI-S). CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo. CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression (63.8% vs. 34.8%, p=0.044) and mania (87.8% vs. 57.1%, p=0.012). Compared to CBZ monotherapy, adjunctive FEWP with CBZ resulted in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects (84.8% vs. 63.8%, p=0.032), but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects. There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy. These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients, particularly for those in depressive phase.

Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2.

Both genetic factors and early life adversity play major roles in the etiology of schizophrenia. Our previous studies indicated that social isolation (SI) during early postnatal development leads to several lasting abnormal behavioral and pathophysiological features resembling the core symptoms of some human neuropsychiatric disorders in mice. The glutamate and dopamine hypotheses are tightly linked to the development of schizophrenia. The cross-talk between glutamate N-methyl-D-aspartate acid receptors and dopamine receptors is associated with histidine triad nucleotide binding protein 1 (HINT1), which is correlated with diverse psychiatric disorders. We examined the effects of SI on schizophrenia-like behavior and used enzyme-linked immunosorbent assays to investigate the expression levels of HINT1, the NR1 subunit of N-methyl-D-aspartate acid receptor, and dopamine type 2 receptor (D2R) in C57 mice. We found that SI leads to a series of schizophrenia-related deficits, such as social withdrawal, anxiety disorder, cognitive impairments, and sensorimotor gating disturbances. These abnormal phenotypes paralleled changes of HINT1, NR1, and D2R. SI may be considered a robust model of the effects of early life stress on the schizophrenia-related behaviors in mice. Potential interactions among HINT1, NR1, and D2R may underlie the behavioral deficits induced by SI.