This unique study of treatment of the mixed state of bipolar I disorder using simultaneous depression and mania response criteria compared divalproex monotherapy versus olanzapine augmentation in a 6-week, randomized, double-blind trial.

Patients (age 18-60 years) with 14-28 days of divalproex monotherapy (blood levels of 75-125 μg/mL) were randomized to augmentation with olanzapine 5-20 mg/day or placebo. Data collected included: Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression for Bipolar Illness (CGI-BP), hospitalizations, concomitant medications, and adverse events (AEs). Primary co-objectives were comparisons of baseline to endpoint changes in HDRS and YMRS. Secondary objectives included comparisons of times to onset (25% reduction) and response (50% reduction) in both HDRS and YMRS, change in CGI-BP, hospitalizations, and safety.

Patients were 59% female, 51% Caucasian, 33% African American, and 14% Hispanic with mean standard deviation (SD) HDRS and YMRS scores of 22.2 (4.5) and 20.9 (4.4). Mean standard error (SE) score changes for the olanzapine (n=100) or placebo (n=101) arms, respectively, were: HDRS, -9.37 (.55) and -7.69 (.54), p=.022; YMRS, -10.15 (.44) and -7.68 (.44), p< .001; and CGI-BP, -1.34 (.11) and -1.06 (.11), p=.056. Times-to-onset (median 7 vs 14 days) and response (median 25 vs 49 days) were significantly shorter for olanzapine augmentation. One olanzapine patient required hospitalization (p=1.0). Treatment-emergent AEs were consistent with previously-published rates.

Six-week olanzapine treatment augmentation was associated with greater and earlier reduction of manic and depressive symptoms in mixed episode patients on divalproex treatment.

To examine the long-term efficacy and safety of quetiapine in combination with lithium (Li) or divalproex (DVP) in the prevention of recurrent mood events (manic, mixed, or depressed).

Patients with bipolar I disorder (DSM-IV, most recent episode manic, mixed or depressed) received open-label quetiapine (400–800 mg/day; flexible, divided doses)+Li/DVP (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL) for up to 36 weeks to achieve ≥12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400–800 mg/day)+Li/DVP or placebo+Li/DVP for up to 104 weeks. Primary endpoint was time to recurrence of any mood event defined by medication initiation, hospitalization, YMRS or MADRS scores ≥20 at two consecutive assessments, or study discontinuation due to a mood event.

1953 patients entered the stabilization phase and 623 were randomized and received ≥1 dose of study medication. Rates of recurrence of a mood event were 20.3% (63/310) vs 52.1% (163/313) for quetiapine and placebo groups, respectively, a risk reduction of 68% (HR 0.32; P<0.0001). Risk reductions were similar for manic and depressed events (HRs 0.30 and 0.33, respectively; P<0.0001). Safety data were consistent with the recognized safety profile of quetiapine. However, a greater incidence of blood glucose ≥126 mg/dL was observed in the quetiapine treatment group.

Maintenance treatment with quetiapine+Li/DVP was significantly more effective than placebo+Li/DVP in increasing the time to recurrence of a mood event in stable patients with bipolar I disorder.

Supported by funding from AstraZeneca Pharmaceuticals LP.

The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.

The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.

In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.

Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).

Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.

There are strong links between circadian disturbance and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However there are no published studies of changes in expression of clock genes or of other neuropeptides related to circadian-rhythm regulation, which may influence recurrent susceptibility after treatment with antidepressant in MDD.

Blood samples were collected from twelve healthy controls and twelve male major depressive patients pre- and post- treated with escitalopram for eight weeks at 4-hour intervals for 24 hours. Outcome measures were the relative expression of mRNA of clock genes (hPERIOD1, hPERIOD2, hPERIOD3, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta) and the levels of serum melatonin, Vasoactive Intestinal Peptide (VIP), cortisol, Adrenocorticotropic Hormone (ACTH), Insulin-like Growth Factor-1(IGF-1) and growth hormone (GH) in twelve healthy controls and twelve pre- and post- treated MDD patients.

Compared with healthy controls, MDD patients showed disruptions in diurnal rhythms of expression of hPERIOD1, hPERIOD2, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta, along with disruptions in diurnal rhythms of release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (hPER1, hCRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted after eight weeks escitalopram treatment, as did elevation of 24-hour levels of VIP and decreases in 24-hour levels of cortisol and ACTH.

These persisted neurobiological changes may play a role in MDD symptoms that are thought to contribute to recurrence vulnerability and in maintenance therapy for a long term.

Professor Liu, President of Shenzhen Kangning Hospital, came to Canada in 2008 and learned that Assertive Community Treatment Team (hospital without walls) might be one of the solutions to the shortage of inpatient beds. I was invited to conduct site visits, consultations, training sessions and workshops for the mental health professionals in Shenzhen since 2009. Doctors and administrative staff from Shenzhen were sent to Toronto, Canada to learn about the program implementation. Finally the Shenzhen ACT in China was established in November 2012.

To describe the development and adaptation of ACT model in Shenzhen China. To report the success and challenges of ACTT development in China.

To define the history and the purpose, its principles, its internal structure, the team composition, team dynamics, the target population, its characteristics of Shenzhen ACT within the demographic context. I will share my subjective experience regarding my observation, my perspectives and a brief comparison with ACT Teams in Toronto, Canada will be highlighted.

The China Shenzhen ACT Team was born in an institutional context where the community mental health care was still novel and not having enough infrastructures to support the work.

The Shenzhen ACT Team is the first ACT in China to experience the effectiveness and efficiency in taking care of severe mentally ill patients in the community. They have successfully implemented ACT service with the support from the hospital, municipal government and the neighbourhood community.

Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.

Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.

The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.

Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.

We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after three weeks of repetitve transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms.

We report six cases (four females) 15–21 years of age with treatment-resistant MDD. Participants had a mean age of 18.7 years and a mean IQ of 102.3. Short echo proton magnetic resonance spectroscopy (H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5cc) before and after rTMS treatment. rTMS was localized to the left DLPFC and applied for 15 consecutive weekdays. Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores (Ham-D).1H-MRS data was analyzed with LCModel to determine glutamate concentration.

Following rTMS, treatment responders (N=4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Ham-D score reduction). Treatment non-responders (N=2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (−10%). Procedures were generally well tolerated with no adverse events.

rTMS is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by Induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement. Transcranial Magnetic Stimulation for Adolescent Depression (TMSAD)

Planning ability as a critical component of executive function has been used to investigate prefrontal cortex (PFC) function in Schizophrenia patients by several neuroimaging studies. However, the changes of PFC activation after effective antipsychotic treatment are still unclear.

The aim of this study is to explore whether there is any variation in the prefrontal hemodynamic response during Tower of London test after 6 weeks’ antipsychotic treatment in schizophrenia patients, and the relationship between the changes in PFC activation and some demographic factors as well as the severity of the patients’ psychiatric symptoms.

40 patients with first-episode schizophrenia were recruited for the present study. 28-channel NIRS (near infrared spectroscopy) was used to measure changes in hemoglobin concentration in the prefrontal cortical surface area during Tower of London (TOL) test—a classic neuropsychological test for planning abilities. The patients were examined before treatment and after six weeks’ treatment with second-generation antipsychotic medicines.

After the short-term treatment, the patients’ TOL test performance and the activations in PFC during the task period did not differ from baseline (P>0.05), although the psychiatric symptoms of the patients were improved significantly(positive subscale score 18.25±2.86 & 12.75±2.60; general psychopathology 33.67±3.65 & 27.00±3.67; PANSS total score 72.25±7.07 & 55.42±7.53; P<0.001).

It suggests that the impairment of cognitive function and the function of the PFC of schizophrenia patients would not be improved with the improvement of psychiatric symptoms, as further support the hypothesis that PFC damage is a durable impairment for schizophrenia.

Saikosaponin B is one of the main ingredients of Bupleurum. Among the many effects of Bupleurum, saikosaponin B may be contributing molecules.human neuroblastoma cell line SH-SY5Y is a tumor cells of low degree of differentiation. Its cell morphology, physiology and biochemical functions similar to normal nerve cells, are widely used to study the mechanism of diseases and drug, of the nervous system.

To investigate the effect of Saikosaponin B on SH-SY5Y cells.

Cultured SH-SY5Y cells and drawed cell growth curve. Then based on the cell growth curve, using hydrogen peroxide of different doses(110?120?130?140?150?160?180?200?220μmol/L) to treated SH-SY5Y cells. At same time, volume fraction 0.05 serum contained Saikosaponin B was added. Cultured SH-SY5Y cells were observed by morphology and tested by the MTT assay.

Less than 140μmol/L hydrogen peroxide, SH-SY5Y cells does not be caused damage. Saikosaponin B of volume fraction 0.05 can relieve the damage of SH-SY5Y cells treated with 140μmol/L hydrogen peroxide, also can increase the survival of the SH-SY5Y cells.

Saikosaponin B can strongly protect the cultured SH-SY5Y cells from damage induced by hydrogen peroxide.

Persistent gaming, despite acknowledgment of its negative consequences, is a major criterion for individuals with Internet gaming disorder (IGD). This study evaluated the adaptive decision-making, risky decision, and decision-making style of individuals with IGD.

We recruited 87 individuals with IGD and 87 without IGD (matched controls). All participants underwent an interview based on the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) diagnostic criteria for IGD and completed an adaptive decision-making task; the Preference for Intuition and Deliberation Scale, Chen Internet Addiction Scale, and Barratt Impulsivity Scale were also assessed on the basis of the information from the diagnostic interviews.

The results demonstrated that the participants in both groups tend to make more risky choices in advantage trials where their expected value (EV) was more favorable than those of the riskless choice. The tendency to make a risky choice in advantage trials was stronger among IGD group than that among controls. Participants of both groups made more risky choices in the loss domain, a risky option to loss more versus sure loss option, than they did in the gain domain, a risky option to gain more versus sure gain. Furthermore, the participants with IGD made more risky choices in the gain domain than did the controls. Participants with IGD showed higher and lower preferences for intuitive and deliberative decision-making styles, respectively, than controls and their preferences for intuition and deliberation were positively and negatively associated with IGD severity, respectively.

These results suggested that individuals with IGD have elevated EV sensitivity for decision-making. However, they demonstrated risky preferences in the gain domain and preferred an intuitive rather than deliberative decision-making style. This might explain why they continue Internet gaming despite negative consequences. Thus, therapists should focus more on decision-making styles and promote deliberative thinking processes to mitigate the long-term negative consequences of IGD.