Effectiveness of medication treatment is determined by three components: treatment efficacy (symptom reduction), tolerability/safety, and adherence. Compared with efficacy and safety, research into adherence has been lacking. Nevertheless, medication non-adherence is a risk factor for relapse and for aggressive behavior in association with substance abuse in schizophrenia patients. Non-adherence has been estimated to cause approximately 40% of relapses in patients with schizophrenia. High rates of treatment discontinuation in all arms of the CATIE study illustrate the widespread nature of non-adherence. Most of previous research has defined non-adherence as a complete discontinuation of medication. However, many schizophrenia patients show partial adherence: they do not completely discontinue their medication, but they do not take all that has been prescribed. Partial adherence is more difficult to define and study than complete non-adherence.

e had the opportunity to study partial adherence in the context of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10mg/d, 20 mg/d and 40 mg/d for patients with schizophrenia or schizoaffective disorder (N=599). Medication non-adherence was measured by pill counts. Baseline characteristics including demographics, illness history and symptom severity were investigated as potential risk factors for treatment non-adherence.

Approximately 1/3 of patients were non-adherent with their medication at least once during the 8-week study. These non-adherent patients had significantly less improvement compared to adherent patients. Adherent patients had greater weight gain than the non-adherent ones. Among the available baseline measures, greater baseline depression severity appeared to be a significant risk factor for non-adherence.

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.

Previous studies have shown that African American youth are over-represented in the Criminal Justice System (CJS). Substance use problems are common among those with CJS involvement. However, less is known regarding racial disparities, among youth with CJS involvement, in receiving substance use treatment services.

To examine racial disparities with regard to receiving treatment services for substance use related problems, among youth with (CJS) involvement.

Data were obtained from the 2006–2008 United States National Survey on Drug Use and Health (NSDUH) in USA. Among White and African American adolescents (Ages 12–17) with recent CJS involvement and who met criteria for alcohol or illicit drug abuse or dependence (N = 602), racial differences in receiving treatment services for substance use problems were examined. Multiple logistic regression analyses were performed to identify predictors of service access among the adolescents, to see if the racial disparity could be explained by individual-level, family-level, and criminal justice system involvement factors.

While 31.2% of White adolescent substance abusers with CJS involvement had received treatment for substance use related problems, only 11.6% of their African American counterparts had received such treatment (P = 0.0005). Multiple logistic regression analyses showed that access to treatment services can be predicted by substance use related delinquent behaviors, but that racial disparities in treatment still exist after adjusting for these factors (AOR = 0.24, 95%CI = (0.09,0.59), P = 0.0027).

There is an urgent need to reduce racial disparities in receiving substance use treatment among U.S. youth with CJS involvement.

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.

This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.

Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.

305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).

Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.

To investigate the effect of Qing huan ling containing serum on proliferation and morphology of human neuroblastoma SH-SY5Y cells.

7 consecutive days gavaged Qing huan ling or Risperidone to rabbit for preparation of Qing huan ling, or risperidone drug-containing rabbit serum. The morphology of SH-SY5Y cells was observed by inverted microscope after 48 hours drug-containing serum treated, and every 24h proliferation of SH-SY5Y cell was tested by the MTT assay.

Qing huan ling containing serum treated 48h SH-SY5Y cell, were close contact between the cells, have pseudopodia, and promote proliferation. Qing huan ling containing serum compared with the blank serum on proliferation of SH-SY5Y cells not statistically significant (P> 0.05), but risperidone containing serum can be a significant increase in the number of SH-SY5Y cells, showing the logarithmic growth trend (P <0.05).

Qing huan ling containing serum can promote on the normal form of the SH-SY5Y cells, on normal proliferation of SH-SY5Y cells without significant intervention, different from the risperidone role.

Multiple neurotrophic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF) and insulin-like growth factor(IGF)-1, have been shown to play important roles in the pathophysiology of mood disorders. However, insufficient clinical data supporting the importance of these neurotrophic factors in mood disorders, especially manic episode, have made inconclusive to make a connection between these factors and the disorder.

This study intended to investigate possible peripheral biomarkers in serum of manic episode of bipolar disorder.

We aimed to investigate whether or not serum levels of VEGF, FGF-2, NGF and IGF-1 varied in manic state.

Serum levels of VEGF, FGF-2, NGF and IGF-1 were examined in 70 drug-naïve patients with manic episode of bipolar disorder (BM) as well as 50 healthy controls, using an ELISA method.

The mean serum levels of VEGF, FGF-2, NGF and IGF-1 were 168.13±225.61pg/ml, 279.09±378.62pg/ml, 61.38±171.67pg/ml and 162.01±72.00ng/ml in BM patients, and 140.80±143.71pg/ml, 275.46±235.29pg/ml, 36.34±15.14pg/ml and 138.90±80.11ng/ml in healthy controls, respectively. Serum levels of FGF-2, NGF and IGF-1 in patients were significantly higher than those in healthy controls (Z=−2.896, P=0.004; Z=− 2.050, P=0.040; Z=−2.188, P=0.029; respectively), although there was no statistical difference in the serum levels of VEGF between two groups (Z=-0.468, P=0.639). Moreover, serum levels of NGF in patients correlated with the duration of disorder (rs=−0.241, P=0.044).

The increase in serum levels of FGF-2, NGF and IGF-1 in manic state may reflect a neuroprotective role for these factors, and these factors may be considered biological markers for manic episode.

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.

Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors.

DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined.

Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving.

These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.

Although alienation toward parents is important for children (for current mental health status or later interpersonal relationships in adulthood), it is undervalued and even lacks a standardized tool of assessment. Moreover, the large number of left-behind children in China is a cause of public concern. However, their experienced alienation toward their parents remains unclear, which may be important for early detection or intervention for behavioral problems in this population. Hence, the current study aimed to develop an alienation inventory for children and then use it to investigate the experienced alienation toward parents in Chinese left-behind children.

Two studies were carried out. Study 1 was designed to develop a standard inventory of alienation toward parents (IAP). In study 2, 8361 children and adolescents (6704 of them were left-behind status) of the Chongqing area, aged between 8 and 19 years old, were recruited for investigation. All participants were surveyed with a standard sociodemographic questionnaire, children's cognitive style questionnaire, children's depression inventory, adolescent self-rating life events checklist, and newly built IAP in study 1.

In study 1, we developed a two-component (communication and emotional distance) and 18-item (9 items for maternal or paternal form, respectively) IAP questionnaire. In study 2, exploratory factor analysis indicated an expected two-factor structure of IAP, which was confirmed by confirmatory factor analysis. The Cronbach's alpha coefficients showed a good reliability (0.887 and 0.821 for maternal and paternal form, respectively). Children with absent mother experienced the highest alienation toward parents. Boys as well as children aged 8–10 years old experienced higher alienation toward parents. Poor communication with parents (sparse or no connection), level of left-behind condition (parents divorced, been far away from parents), and psychosocial vulnerability (stressful life events, negative cognitive style) were risk factors of alienation toward parents.

The current study develops a two-factor (communication and emotional distance) IAP, which offers a reliable tool to assess experienced alienation of affection toward parents in children aged between 8 and 19 years old. Our result is the first investigation of experienced alienation and potential influential factors in Chinese left-behind children. The findings that children with absent mother experience higher alienation toward parents, as well as three recognized risk factors for alienation of affection toward parents (poor communication with absent parents, worse left-behind condition, and psychosocial vulnerability), give valuable guidance for parents who intend to leave or who are already leaving as well as for government policymaking.

To observe the effect of Qing Huan Ling and (or) risperidone on locomotor activity and explorative behavior of schizophrenia mice model by open field test.

Seventy kunming mice were randomly divided into 5 groups, one group as blank group. The rest groups ip MK-801 continuously 14 day, then randomly numbered: model group, risperidone group, Qing Huan Ling group and risperidone combined Qing Huan Ling group. Ig give corresponding drugs for each group 4 weeks, observe the change of locomotor activity and explorative behavior by open field test.

After Ig 4 weeks, compared with the blank group, there were no obvious difference in locomotor activity and explorative behavior between risperidone group, Qing Huan Ling group and the combined group. Compared with the model group, risperidone had statistics meaning in the repression of explorative behavior (P < 0.05),the combined group has statistics meaning in the repression of locomotor activity and explorative behavior (78.92 ± 36.18 m vs. 186.92 ± 41.08 m, P < 0.01).

Qing Huan Ling regulate the central nervous system of schizophrenia mice model; when combined with risperidone, it restrain the central nervous system of schizophrenia mice model and the effect is stronger than risperidone alone.

The authors have not supplied their declaration of competing interest.