Background It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. Methods This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. Results At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). Conclusions Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. Trial registration This study was registered on Clinicaltrials.gov (NCT03451734).

Objectives To investigate the improvement effect of occipital repetitive transcranial magnetic stimulation (rTMS) combined with escitalopram oxalate tablets on pre-attentive processing in patients with first-episode, medication-naive depression. Methods Patients who were hospitalized between January and December 2019 were selected. They were randomly allocated to real occipital rTMS stimulation group with 27 cases receiving intermittent theta-burst (iTBS) and sham stimulation group with 24 cases over 20 days. The rTMS treatment target is located at the Oz point of the occipital region. Both groups took escitalopram oxalate tablets, and the average daily drug dose was 15.294 ± 5.041 mg. Hamilton Depression Rating Scale (HAMD) was used to assess the symptoms of depression before and after treatment, and mismatch negativity (MMN) was used to assess the improvement of pre-attentive processing before and after treatment. Results After 20 days of treatment, the total score of HAMD (13.495 ± 3.700) in both groups was significantly lower than that before treatment [21.910 ± 3.841, F (1, 49) = 46, 3.690, p < 0.001]. After treatment, the latency of MMN in the real stimulation group (182.204 ± 31.878 ms) was significantly lower than that in the sham stimulation group (219.896 ± 42.634 ms, p < 0.001), and the amplitude of MMN in the real stimulation group (−7.107 ± 3.374 ms) was significantly higher than that in the sham stimulation group (−2.773 ± 3.7 32 ms, p < 0.001). Conclusion Occipital rTMS treatment can enhance the early therapeutic effect and effectively improve the pre-attentive processing of patients with depression and provide a scientific basis for the new target of rTMS therapy in clinical patients with depression.

目的:探究氨磺必利对精神分裂症伴抑郁患者正负性情绪及应对方式的影响.方法:招募精神分裂症伴抑郁患者60例作为研究组,予以氨磺必利治疗4周.另选取健康志愿者20例作为对照组.比较两组治疗前正负性情绪量表(PANAS)及特质应对方式问卷(TCSQ)评分.比较研究组治疗前后简明精神病评定量表(BPRS)、PANAS、TCSQ及贝克抑郁自评量表(BDI)评分.结果:治疗前,研究组正性情绪、积极应对方式评分低于对照组,而负性情绪、负性应对方式评分高于对照组(均P<0.05).治疗后,患者BPRS及BDI评分降低(均P<0.05);正性情绪评分和积极应对方式评分明显高于治疗前(均P<0.05),负性情绪评分和消极应对方式评分与治疗前比较无统计学差异(均P>0.05).结论:氨磺必利可改善精神分裂症伴抑郁患者精神症状及部分抑郁症状,负性情绪、消极应对方式可能是患者经药物治疗后社会功能恢复欠佳的重要因素.

目的:探讨P300在舍曲林治疗抑郁障碍中的应用效果.方法:对28名首发抑郁障碍患者使用舍曲林治疗4周,对比其治疗前和治疗后汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评分及P300成份变化.结果:经过4周舍曲林治疗,抑郁障碍患者HAMD评分显著降低.治疗后P300成份的波幅较治疗前增高(P＜0.05),潜伏期无明显变化.结论:舍曲林可显著改善首发抑郁障碍患者临床症状,可部分改善认知功能,P300可作为评估抑郁障碍患者病情变化的有效工具.

Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment. We found that high-frequency rTMS (HrTMS, 15 Hz) treatment significantly relieved the impaired glutamatergic receptors in the ACC after SPS treatment by significantly increasing NMDAR and AMPAR expression. Simultaneously, HrTMS blocked inhibited neuronal phosphatase and tensin homologue on chromosome 10 (PTEN)/Akt signalling in the ACC after SPS treatment by decreasing PTEN expression and increasing Akt phosphorylation, which is critically involved in the regulation of memory and synaptic plasticity. The PTEN inhibitors bpV and small interfering RNA and the Akt inhibitor wortmannin were stereotaxically administered to the ACC after SPS treatment to advance the mechanistic study. Analysis by Western blot, double immunofluorescence, Golgi staining and behavioural tests demonstrated that the effects of rTMS on PTEN/Akt activation, glutamatergic receptor expression, neuronal synaptic plasticity and PTSD-related behaviours induced by SPS treatment were enhanced by PTEN inhibition and blocked by Akt inhibition in the ACC. Our study provides convincing evidence for the effectiveness of rTMS treatment on PTSD and suggests that its potential mechanism involves remodelling neuronal synaptic plasticity via the PTEN/Akt signalling pathway.

目的:探讨紧张症的症状特征、病因诊断及短期转归,为提高紧张症的诊断及治疗有效率提供依据.方法:纳入符合美国精神障碍诊断与统计手册第五版(DSM-5)中紧张症诊断标准的住院患者,使用Bush-Francis紧张症量表完成症状及严重程度评估;于12个月后进行电话随访.结果:32例紧张症患者中,最终诊断精神分裂症13例(40.63％),分裂样精神病6例(18.75％),抑郁症6例(18.75％),双相情感障碍抑郁发作3例(9.38％),痴呆1例(3.13％),脑梗死1例(3.13％),精神发育迟滞1例(3.13％),恶性综合征1例(3.13％).最常见的紧张症症状为凝视(29例,90.6％)、木僵(27例,84.4％)及持续姿势/强直(27例,84.4％),18例(56.25％)患者进行了电休克治疗.12个月随访结果提示2例仍有部分症状,1例诊断分裂样精神病的患者纠正诊断为双相情感障碍,1例患者因紧张症再次发作入院.结论:紧张症最常见的诊断为精神分裂症及分裂样精神病,各类诊断预后差异较大.

Background Repetitive transcranial magnetic stimulation (rTMS) has been employed for decades as a non-pharmacologic treatment for post-traumatic stress disorder (PTSD). Although a link has been suggested between PTSD and impaired sensorimotor gating (SG), studies assessing the effects of rTMS against PTSD or PTSD with impaired SG are scarce. Aim To assess the benefit of rTMS in a rat model of PTSD. Methods Using a modified single prolonged stress (SPS&S) rat model of PTSD, behavioral parameters were acquired using open field test (OFT), elevated plus maze test (EPMT), and prepulse inhibition trial (PPI), with or without 7 days of high frequency (10Hz) rTMS treatment of SPS&S rats. Results Anxiety-like behavior, impaired SG and increased plasma level of cortisol were observed in SPS&S animals after stress for a prolonged time. Interestingly, rTMS administered immediately after stress prevented those impairment. Conclusion Stress-induced anxiety-like behavior, increased plasma level of cortisol and impaired PPI occur after stress and high-frequency rTMS has the potential to ameliorate this behavior, suggesting that high frequency rTMS should be further evaluated for its use as a method for preventing PTSD.

Objective:To compare the effects of olanzapine combined with repetitive transcranial magnetic stimulation (rTMS) or modified electric convulsive (MECT) therapy on schizophrenia.Methods:A total of 84 cases of patients with schizophrenia were collected and divided into the olarnzapine plus MECT (n=42) and the olanzapine plusrTMS group (n=42).The positive and negative symptom scale (PANSS) was used to evaluate the efficacy at the end of2nd,4th and 8th week after treatment.The adverse reactions Scale (TESS)was introduced to evaluate the adverse reactions.The cognitive function was evaluated with Weschler Memory Scale (WMS) and Wisconsin Card Test (WCST).Results:There was no significant difference in the total effective rate,total score of PANSS,positive symptoms,negative symptoms and general pathological symptoms betwwen MECT and rTMS group (P＞0.05).But the total score of PANSS,positive symptoms,negative symptoms and general pathological symptoms were significantly decreased (P＜0.05,P＜0.01) after treatment.There was no significant difference in the incidence of adverse reactions between rTMS and MECT group (P＞0.05).However,the cognition was obviously ameliorated following treatment with olanzapine plus rTMS or MECT (P＜0.05,P＜0.01).and higher improvement in memory and execution capacity was observed in olanzapine plus rTMS groups,when compared with olanzapine plus MECT group (P＜0.05).Conelusions:The combined application of olanzapine with rTMS or MECT had the similar efficacy in the treatment of schizophrenia,but the former exhibited the higher therapeutic effect on the improvement of cognitive function.

Objective To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with risperidone to improve white matter integrity on left hippocampus in patients with first-episode schizophrenia.Methods A total of 28 patients with schizophrenia were randomly divided into study group with rTMS combined with risperidone and control group with sham-rTMS combined with risperidone for 6 weeks of treatment.They were assessed with Positive and Negative Syndrome Scale (PANSS) and examined with diffusion tensor imaging(DTI) before and after treatment.Results The total score and all factor scores of PANSS in both groups after treatment were all significantly lower than those before treatment(P ＜ 0.05).In study group,the FA value of white matter on left hippocampus after treatment was significantly higher than that before treatment(P ＜0.05)and the positive factor score of PANSS was significantly lower than that in control group(P ＜ 0.05).In study group,the increased FA value was positively correlated with the decreased positive factor score of PANSS (P ＜ 0.05).Conclusion It's effective for rTMS combined with risperidone to improve the clinical symptoms and white matter integrity on left hippocampus in patients with first-episode schizophrenia and there exists some correlation between them.

Objective:To compare the efficacy and safety of Paliperidone palmitate and long-acting injectable risperidone (LAIR)in treatment of patients with schizophrenia.Methods:43 schizophrenic patients in study group were treated with Paliperidone palmitate and 53 schizophrenic patients in control group were treated with LAIR.The treatment lasted for 12 weeks.The patients were assessed with Positive and Negative Symptoms Scales (PANSS),Personal and Social Performance Scale (PSP),Treatment Emergent Symptom Scale (TESS),Barnes Akathisis Scale (BARS) and Abnormal Involuntary Movement Scale (AIMS).At the same time,the weights,waistlines,ECGs were detected and the side-effects of both drugs were evaluated.Results:The overall clinical symptoms and the social function were obviously improved after Paliperidone or LAIR treatment (P ＜ 0.05),but there were no significant differences in the scores ofPANSS (F =0.918,P =0.405) and PSP (P =0.134) between two groups when analyzed by Contour Analysis or Covafiance Analysis.Both drugs induced limited weight changes and extra pyramidal symptoms,and the electrocardiogram index,physical examination and vital signs as well.Conclusions:The efficacy and safety are comparable between Paliperidone palmitate and LAIR.

Objective To compare the antidepressive effect and cognitive imfluence of modified electroconvulsive therapy(MECT) and repetitive transcranial magnetic stimulation(rTMS) on medica-tion-resistant depression patients.Methods Totals of 40 patients with treatment-refractory and non-psy-chotic major depression were randomly divided into MECT group and rTMS group. They received two weeks of treatments with either MECT or rTMS and were assessed for efficacy and cognitive impairments before and after 1 and 2 weeks treatment by Hamilton Rating Scale for Depression(HAMD) and Clinical Memory Scale. Treat-ment Emergent Symptom Scale(TESS) was used to evaluate the side-effects. Moreover, medical examination, electrocardiogram and electroencephalogram examination were performed before and after treatment for safety. Results There was no difference between two groups before and at the end of week 1 and 2 on the total HAMD score(P=0.610,P=0.235) and cognitive impairment factors(P=0.639,P=0.793). However, Clinical Memo-ry Scale score and all factors of rTMS group was improved markedly at the end of week 2(P<0.05). Directed memory score, free recall deficit of picture score, image free recall score and portrait character recall score of MECT group was declined at the end of week 2(P<0.05). And the total score, directed memory score and por-trait character recall score of MECT group was lower than that of rTMS group(P<0.05). There was no significant difference between the two groups on the incidence of nausea, vomiting, headache(P>0.05), and more patients complained of memory decline in the MECT group(P<0.05).Conclusions rTMS and MECT have similar effi-cacy in treating treatment-refractory non-psychotic major depression. But rTMS is benefit to the improvement of cognitive performance with more safety than MECT.

Repetitive transcranial magnetic stimulation (rTMS) is a useful monotherapy for depression or adjunctive therapy for resistant depression. However, the anti-depressive effects of different parameters and the underlying mechanisms remain unclear. Here, we aimed to assess the effect of rTMS with different parameters (1/5/10 Hz, 0.84/1.26 T) on the depressive-like behaviors, 5-hydroxytryptamine (5-HT), 5-HIAA (5-hydroxyindoleacetic acid) and DA and NE levels, and monoamine oxidase A (MAO-A) activity in chronic unpredictable stress-treated rats, along with the expression of sirtuin 1 (Sirt1) and MAO-A in the prefrontal cortex (PFC) and cortex-derived astrocytes from new-born rats. Moreover, the depressive-like behaviors were monitored following the transcranial injection of the Sirt1 inhibitor EX527 (1 mM) daily for 1 week. We found that rTMS treatment (5/10 Hz, 0.84/1.26 T) ameliorated depressive-like behaviors, increased 5-HT, DA and NE levels, decreased the 5-HIAA level and Sirt1 and MAO-A expression, and reduced MAO-A activity in the PFC. The depressive-like behaviors were also ameliorated after the transcranial injection of EX527. Importantly, rTMS (5/10 Hz, 0.84/1.26 T) inhibited Sirt1 and MAO-A expressions in astrocytes and Sirt1 knockdown with short hairpin RNA decreased MAO-A expression in astrocytes. These results suggest that the inhibition of Sirt1/MAO-A expression in astrocytes in the PFC may contribute to the different anti-depressive effects of rTMS with different parameters, and may also provide a novel insight into the mechanisms underlying major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) may have the potential to prevent depressive relapse. This assessor-blinded, randomized controlled study was designed to evaluate the efficacy and safety of rTMS as a mono- and combination therapy in the prevention of depressive relapse/recurrence. A total of 281 depressed patients who had achieved stable full or partial remission on a 6-month antidepressant (ADP) run-in treatment were randomly assigned to an rTMS ( n = 91), ADP ( n = 108), or combined (rTMS + ADP, n = 82) treatment group for 12 months. Monthly clustered rTMS was conducted in 5–10 sessions over a 3–5-day period. Maintenance outcomes were assessed using time to relapse/recurrence and relapse/recurrence rate. Overall, 71.2% (200/281) of the participants completed the treatment per the protocol. rTMS + ADP and rTMS significantly reduced the risk of relapse/recurrence compared with ADP ( P = 0.000), with hazard ratios of 0.297 and 0.466, respectively. Both rTMS-containing regimens produced significantly lower relapse/recurrence rates than ADP (15.9% and 24.2% vs. 44.4%, P < 0.001). In the relapsed/recurrent subgroup, first-episode depressed, rTMS-treated patients had a markedly lower relapse/recurrence rate than ADP-treated patients. Five patients on the ADP-containing regimens, but none on rTMS alone, developed acute mania. The rTMS-containing regimens had considerably more certain side effects than did the ADP group. We concluded that TMS, whether as a mono- or additional therapy, is superior to antidepressants in preventing depressive relapse/recurrence, particularly in first-episode depressed patients. The treatment does not increase the risk of manic switch, but may increase the risk of certain side effects.

Background: Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited.Objective: This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD).Methods: In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared.Results: The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens.Conclusions: We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome. (C) 2016 Elsevier Ltd. All rights reserved.

Objective To explore the effects of quetiapine(QUE) on viability and proliferation in LPS injured hippocampal -derived neural stem cells (NSCs) and investigate the role of ERK signal path‐way .Methods The NSCs were derived from hippocampus of fetal rats ,and divided into Sham group , LPS group and LPS+QUE group (including 0 .5 ,1 and 2μmol/L) .Then the cell viability ,the expres‐sion of pERK1/2 and BrdU labeling and detection were measured by the kit of WST -8 ,Western Blot and immunocytochemical method after 48 h ,respectively .Furthermore ,the cell viability and BrdU labe‐ling and detection were also detected after U 0126 treatment to clear the role of ERK signal pathway .Re‐sults (1)Cell viability test showed that the viability of LPS group [A= (0 .251 ± 0 .034) ] was signifi‐cantly lower than that of Sham group [A= (0 .371 ± 0 .027)] ,LPS+ QUE 1μmol/L group [A= (0 .311 ± 0.018)] and LPS+QUE 2 μmol/L group [A= (0 .343 ± 0 .021)] (P < 0 .05) .(2)The expression of pERK1/2 in LPS group (0 .313 ± 0 .124) was significantly lower than that of Sham group (1 .417 ± 0.141) ,LPS+QUE 1μmol/L group (0 .681 ± 0 .098) and LPS+QUE 2μmol/L group (0 .954 ± 0 .119) as detected by Western Blot .(3)The percentage of BrdU+ cells in LPS group (23 .098 ± 2 .153)% was significantly lower than that of Sham group (40 .388 ± 2 .910)% ,LPS+ QUE 1 μmol/L group (28 .742 ± 1 .536)% and LPS+QUE 2μmol/L group (31 .369 ± 2 .313)% .(4)The effects of QUE (1μmol/L and 2μmol/L) were inhibited by U0126 .Conclusions The damage of cell viability and proliferation of NSCs induced by LPS can be restrained by QUE ,and this effect might be related to the activation of ERK sig‐naling pathw ay .

目的：探讨青少年双相情感障碍患者首次发作时症状特点、精神病性症状的特征及诊断情况，为青少年双相情感障碍的及时诊断提供依据.方法本研究为回顾性研究，对2010年1月1日~2015年10月31日于第四军医大学西京医院心身科住院，年龄13~17岁，诊断为首次发作双相情感障碍的119例患者的临床特征及精神病性症状的特点进行总结分析.结果首次就诊误诊86例，占72.26％；其中，躁狂发作误诊14例，出现精神病性症状的为12例，误诊8例(66．67％)；抑郁发作误诊71例，伴精神病性症状的为26例，误诊24例(92．31％).混合发作误诊1例，且伴精神病性症状.在首次发作的双相障碍的患者中，精神病性症状出现最频繁的为关系妄想(27例)，其次为幻觉(10例).结论精神病性症状对于首次为抑郁发作的青少年患者来说对确诊双相情感障碍的意义更大.青少年双相请障碍患者出现精神病性症状的形式、内容广泛.重视精神病性症状在青少年双相障碍中的诊断作用，对提高双相障碍的识别率、诊断率有重大意义.

A 56-year old Chinese female was referred to an academic medical center with atypical, treatment-resistant depression that continued for approximately 3years after her sister's death.Comprehensive evaluation including neurocognitive testing, EEG, spinal tap, HIV testing and brain MRI revealed behavioral variant of fronto-temporal dementia (bvFTD) with significant frontal and temporal lobe atrophy.This patient's unusual clinical presentation emphasizes the overlap between depression and bvFTD, and underlines the importance of prompt, accurate diagnosis to minimize often-ineffective pharmacological interventions and caregiver burnout.

Objectives An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. Methods Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. Results Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ2 = 4.010, P = 0.045) and menstrual resumption (χ2 = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. Conclusions Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

Background: White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown. Methods: The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period. Results: Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167. Conclusions: The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs.

Quetiapine (QUE) and repetitive transcranial magnetic stimulation (rTMS) have been considered to be possible monotherapies for depression or adjunctive therapies for the treatment of the resistant depression, but the underlying mechanisms remain unclear. The present study aimed to assess the effects of combined QUE and rTMS treatment on depressive-like behaviors, hippocampal proliferation, and the in vivo and in vitro expressions of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) and brain-derived neurotrophic factor (BDNF) in male Sprague–Dawley rats. The administration of QUE and rTMS was determined not only to reverse the depressive-like behaviors of rats exposed to chronic unpredictable stress (CUS) but also to restore the protein expressions of pERK1/2 and BDNF and cell proliferation in the hippocampus. Additionally, QUE and rTMS promoted the proliferation and increased the expression of pERK1/2 and BDNF in hippocampal-derived neural stem cells (NSCs), and these effects were abolished by U0126. Taken together, these results suggest that the antidepressive-like effects of QUE and rTMS might be related to the activation of the BDNF/ERK signaling pathway and the up-regulation of cell proliferation in the hippocampus.