Molecular Mapping of Sebaceous Squalene by Ambient Mass Spectrometry.

Squalene (SQ), a highly unsaturated sebaceous lipid, plays an important role in protecting human skin. To better understand the role of SQ in clinical medicine, an efficient analytical approach is needed to comprehensively study the distribution of SQ on different parts of the skin. In this study, sebaceous lipids were collected from different epidermal areas of a volunteer with sampling probes. Thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was then used to characterize the lipid species on the probes, and each TD-ESI/MS analysis was completed within a few seconds without any sample pretreatment. The molecular mapping of epidermal squalene on whole-body skin was rendered by scaling the peak area of the extracted ion current (EIC) of SQ based on a temperature color gradient, where colors were assigned to the 1357 sampling locations on a 3D map of the volunteer. The image showed a higher SQ distribution on the face than any other area of the body, indicating the role of SQ in protecting facial skin. The results were in agreement with previous studies using SQ as a marker to explore sebaceous activity. The novelty and significance of this work are concluded as two points: (1) direct and rapid detection of all major classes of sebaceous lipids, including the unsaturated hydrocarbons (SQ) and nonpolar lipids (e.g., cholesterol). The results are unique compared to other conventional and ambient ionization mass spectrometry methods and (2) this is the first study to analyze SQ distribution on the whole-body skin by a high-throughput approach.

Association between paternal age and risk of schizophrenia: a nationwide population-based study.

PURPOSE: To study the association between paternal age and schizophrenia in offspring. METHODS: This report describes a nationwide population-based cohort study from 1997 to 2013. Data from Taiwan's National Health Insurance Research Database were utilized to answer the research question. A total of 17,649 offspring with schizophrenia were selected from 11 million offspring in the general population. Additionally, we established the offspring without schizophrenia as the comparison group by matching the study cohort by age, gender in a 1:4 ratio (n = 70,596). RESULTS: The median age at first presentation with schizophrenia was 20 years (interquartile range (IQR), 17 to 24). Comparison of the schizophrenia and non-schizophrenia groups indicated that father's age at birth (30.0 (IQR), 27 to 33 vs. 29.0 (IQR), 26 to 32 years), mother's age at birth (26.0 (IQR), 24 to 29 vs. 26.0 (IQR), 23 to 29 years), paternal schizophrenia (2.6% vs. 0.6%), and maternal schizophrenia (4.4% vs. 0.7%) were all significantly greater in the schizophrenia group. In addition, each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia (model 1: aOR = 1.22; 95% CI 1.20, 1.24; model 2: aOR = 1.20; 95% CI 1.18, 1.23). Subgroup analysis showed that each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia in male and female offspring, as well as in offspring of mothers and fathers with or without schizophrenia (aOR = 1.20 to 2.20, all p values < 0.01). CONCLUSION: This study indicated that advanced paternal age increased the risk of schizophrenia in offspring. Offspring born to fathers older by 5-year increments were at heightened risk of schizophrenia.

Excited catatonia in a patient with fatal pulmonary embolism and a successful treatment strategy.

BACKGROUND: Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy. CASE PRESENTATION: The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event. CONCLUSION: This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.

Serum Brain-Derived Neurotrophic Factors in Taiwanese Patients with Drug-Naïve First-Episode Major Depressive Disorder: Effects of Antidepressants.

Background: Brain-derived neurotrophic factors are known to be related to the psychopathology of major depressive disorder. However, studies focusing on drug-naïve first-episode patients are still rare. Methods: Over a 6-year period, we examined the serum brain-derived neurotrophic factors levels in patients with first-episode drug-naïve major depressive disorder and compared them with sex-matched healthy controls. We also investigated the relationships between serum brain-derived neurotrophic factors levels, suicidal behavior, and Hamilton Depression Rating Scale scores before and after a 4-week antidepressant treatment. Results: The baseline serum brain-derived neurotrophic factors levels of 71 patients were significantly lower than those of the controls (P=.017), and the Hamilton Depression Rating Scale scores in 71 patients did not correlate with brain-derived neurotrophic factor levels. Brain-derived neurotrophic factor levels were significantly lower in 13 suicidal major depressive disorder patients than in 58 nonsuicidal major depressive disorder patients (P=.038). Among 41 followed-up patients, there was no alteration in serum brain-derived neurotrophic factors levels after treatment with antidepressants (P=.126). In receiver operating characteristic curve analysis of using pretreatment brain-derived neurotrophic factors to estimate the response to treatment, the area under the curve was 0.684. The most suitable cut-off point was 6.1 ng/mL (sensitivity=78.6%, specificity = 53.8%). Conclusions: Our data support the serum brain-derived neurotrophic factor levels in patients with drug-naïve first-episode major depressive disorder were lower than those in the healthy controls, and patients with pretreatment brain-derived neurotrophic factors >6.1 ng/mL were more likely to be responders. Although the relationship of our results to the mechanism of drug action and pathophysiology of depression remains unclear, the measure may have potential use as a predictor of response to treatment. In the future, it needs a large sample to prove these results.

TNFAIP3, a negative regulator of the TLR signaling pathway, is a potential predictive biomarker of response to antidepressant treatment in major depressive disorder.

Inflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants. Positive regulators of the TLR4 pathway, including Pellino 1, TRAF6 and IRAK1, were also investigated. Among all patients, MyD88s, and TNFAIP3 mRNAs were expressed at lower levels in PBMCs from patients with MDD. Multiple linear regression analyses revealed that TNFAIP3 mRNA expression before treatment was inversely correlated with severity of depression and effectively predicted improvement in HAMD-17 scores. Among 79 treatment-completers, only TNFAIP3 mRNA was significantly increased by treatment with antidepressants for 4 weeks. Treatment of human monocytes (THP-1) and mouse microglia (SIM-A9) cell lines with fluoxetine significantly increased TNFAIP3 mRNA expression and suppressed IL-6 levels. The suppressive effect of fluoxetine on IL-6 was attenuated by knockdown of TNFAIP3 expression. These findings suggest that both dysfunction of the negative regulatory system in patients with MDD and antidepressant treatment exert anti-inflammatory effects, at least in part through increased expression of the TNFAIP3 gene. They also indicate that modulating expression of the TNFAIP3 gene to rebalance TLR-mediated inflammatory signaling may be potential therapeutic strategy for treating MDD.

TNFAIP3 mRNA Level Is Associated with Psychological Anxiety in Major Depressive Disorder.

BACKGROUND: Major depressive disorder has been shown to be associated with inflammation and the dysregulation of innate immune responses. Previously, we showed an inverse correlation between the severity of depression and level of TNFAIP3 mRNA expression. The present study further evaluated the association between TNFAIP3 mRNA expression level and symptoms of major depressive disorder (MDD) in 91 patients (20 men and 71 women). METHODS: The relationships between subscores on the 17-item Hamilton Depression Rating Scale (HAMD-17) and TNFAIP3 mRNA levels were assessed by multiple linear regression. RESULTS: Only psychological anxiety on the HAMD-17 correlated significantly with TNFAIP3 mRNA expression. Other symptoms, such as depressed mood, insomnia, work and activities, and suicide, were not associated with TNFAIP3 mRNA expression. CONCLUSION: These findings suggest a significant association between anxiety and TNFAIP3 mRNA levels in patients with MDD.

Periodic catatonia with long-term treatment: a case report.

BACKGROUND: Periodic catatonia has long been a challenging diagnosis and there are no absolute guidelines for treatment when precipitating factors are also unclear. We report a schizophrenia patient with periodic catatonia with a 15-year treatment course. A possible correlation between decreased daylight exposure and periodic attacks has been observed. CASE PRESENTATION: We describe a 49-year-old woman with periodic catatonia associated with schizophrenia with 15 years of follow-up. The patient was treated with the antipsychotics risperidone, haloperidol, loxapine and quetiapine, but catatonia still relapsed once per year during the first few years of her disease course. The treatment was consequently been switched to clozapine due to fluctuated psychotic illness, and a longer duration of remittance was achieved. Lorazepam-diazepam protocol was used for rapid relief of catatonic symptoms, and was able to significantly shorten the duration of the symptoms. In addition, we observed a possible correlation between catatonic episodes and decreased daylight exposure during the 15-year duration. CONCLUSIONS: Successful treatment of acute periodic catatonia was achieved with a lorazepam-diazepam protocol, and the patient remained in remission for a longer duration under clozapine treatment. Besides, the possibility of decreased daylight exposure acting as a precipitating factor was observed during our 15 years of follow-up.

Decreased S100B serum levels after treatment in bipolar patients in a manic phase.

BACKGROUND: Previous studies have suggested that patients with bipolar disorder might have brain damage. The aim of this study was to investigate the serum levels of brain injury biomarkers and S100A10 in bipolar patients in a manic phase, and evaluate the changes in S100B, neuron specific enolase (NSE), heat shock protein 70 (HSP70) and S100A10 after treatment. METHOD: We consecutively enrolled 17 bipolar inpatients in a manic phase and 30 healthy subjects. Serum brain injury biomarkers and S100A10 were measured with assay kits. All patients were evaluated by examining the correlation between brain injury biomarkers and Young Mania Rating Scale (YMRS) scores. RESULT: We found significantly decreased S100B levels only in bipolar manic patients after treatment (p=0.002), but S100B levels were not significantly different from those in healthy controls (p>0.05). CONCLUSION: Our results indicate there were decreased S100B serum levels in bipolar patients in a manic phase after treatment and that increased serum S100B levels might be a possible indicator of transient disruption of the blood-brain barrier in bipolar patients in a manic phase.

Rapid detection of alteration of serum IgG in patients with schizophrenia after risperidone treatment by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry.

RATIONALE: The aim of the study was to use a technique that combines acid hydrolysis and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) in order to detect the serum biomarkers of patients diagnosed with schizophrenia both before and after four-week antipsychotic treatment with risperidone. METHODS: During this study's two-year period, inpatients were diagnosed with schizophrenia using the Structured Clinical Interview for DSM-IV Axis I Disorders. Severity was then evaluated using the Positive and Negative Syndrome Scale both at baseline and at endpoint following four-week treatment with risperidone. The patients' serum biomarkers were quickly measured using acid hydrolysis and MALDI-TOF MS. The resulting peptides were then analyzed using MALDI-TOF MS. We constructed a receiver operating characteristic (ROC) curve for the evaluated biomarkers. RESULTS: We recruited 20 pairs of participants for this study. The experimental group was treated with serum protein with HCl for 10 minutes to effectively hydrolyze abundant proteins. The target peptide, the immunoglobulin gamma chain (IgG), was then rapidly detected using this manner. A significant difference was found in the IgG levels of patients with schizophrenia before and after antipsychotic treatment. We constructed a ROC curve based on the IgG, and the area under said curve was 0.969. In comparison to conventional detection protocols, this method takes only minutes to complete and is also less costly. CONCLUSIONS: This study found that applying acid hydrolysis with MALDI-TOF MS technology could rapidly differentiate serum IgG levels in patients with schizophrenia before and after being treated with risperidone. This IgG difference may enhance the understanding of mechanism of antipsychotic treatment of schizophrenia. Copyright © 2016 John Wiley & Sons, Ltd.

Relapses and recurrences of catatonia: 30-case analysis and literature review.

OBJECTIVE: Relieving catatonia helps identify the underlying etiology and its treatment. However, catatonia may reemerge after some time, but there are few data on the relapses and recurrences of catatonia. We aimed to investigate the characteristics of patients with relapses or recurrences of catatonia as well as the efficacy of the lorazepam-diazepam protocol on them. METHODS: Patients with catatonia who had more than one episode of catatonia and were treated with the lorazepam-diazepam protocol were identified. Their medical charts were reviewed, and interview was conducted. RESULTS: Thirty patients were identified. Nineteen (63.3%) were diagnosed with schizophrenia, five (16.7%) with major depressive disorder, two (6.7%) with bipolar disorder, and four (13.3%) with general medical conditions. In the 68 relapses and relapses the lorazepam-diazepam protocol was used, full response was reported in 54 (79.4%) of them. Twelve of 19 (63.2%) patients with schizophrenia were treated with clozapine. Twenty (66.7%) out of 30 patients were maintained on oral lorazepam by the time of discharge. Literature review showed similar prevalence of schizophrenia in patients with more than one episode of catatonia, and a wide variety of treatment options. CONCLUSION: The lorazepam-diazepam protocol was mostly effective in managing relapses and recurrences of catatonia. Maintenance clozapine and oral lorazepam were beneficial in a significant number of patients.

2D-DIGE proteome analysis on the platelet proteins of patients with major depression.

INTRODUCTION: Platelet activation is related to the psychopathology of major depression. We attempted to search and identify protein biomarkers from the platelets of patients with major depression. High resolution two-dimensional Differential Gel Electrophoresis (2D-DIGE), the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), Western blot, and bioinformatic tools were applied to examine the platelet proteins of 10 patients with major depression and 10 healthy controls. RESULTS: The levels of 8 proteins were significantly different between the patients with major depression in the acute phase and healthy controls. The levels of protein disulfide-isomerase A3 (PDIA3) and F-actin-capping protein subunit beta (CAPZB) were higher in patients with major depression than in healthy controls. The levels of fibrinogen beta chain (FIBB), fibrinogen gamma chain (FIBG), retinoic acid receptor beta (RARB), glutathione peroxidase 1 (GPX1), SH3 domain-containing protein 19 (SH319), and T-complex protein 1 subunit beta (TCPB) were lower in patients with major depression than in healthy controls. CONCLUSIONS: Platelet provided valuable information about the pathways and processes of inflammation/immunity, oxidative stress, and neurogenesis, related to major depression.

Lorazepam-diazepam protocol for catatonia in schizophrenia: a 21-case analysis.

OBJECTIVES: Catatonia is a unique clinical phenomenon characterized by concurrent motor, emotional, vegetative and behavioral signs. Benzodiazepines (BZD) and electroconvulsive therapy (ECT) can rapidly relieve catatonic signs. The lorazepam-diazepam protocol presented here has been proven to relieve catatonia in schizophrenia within a day. METHODS: From July 2002 to August 2011, schizophrenic patients requiring psychiatric intervention for catatonia in Kaohsiung Chang Gung Memorial Hospital were studied by medical chart review. The study used the Bush-Francis Catatonia Rating Scale (BFCRS). Patients receiving the lorazepam-diazepam protocol were identified. RESULTS: The survey included 21 patients (eight males and 13 females) with a mean age of 30.3 ± 12.6 years. Mean duration of schizophrenia was 4.7 ± 5.6 years. Thirteen (61.9%) patients responded within 2 h, 18 (85.7%) responded within one day, and all became catatonia-free within a week. Mean BFCRS score was 9.9 ± 3.0 before treatment. Patients that responded with a single intramuscular lorazepam injection had mean BFCRS score of 8.9 ± 2.8, significantly lower than the mean score (11.6 ± 2.5) of the rest of the patients (p = 0.034). CONCLUSIONS: The lorazepam-diazepam protocol can rapidly relieve retarded catatonia in schizophrenia. Most patients became catatonia-free within one day but some may require up to a week. ECT should be considered if the protocol fails.

Association between programmed death-1 pathway and major depression.

OBJECTIVES: Major depression (MD) may be associated with inflammation and immunity. PD-1 (programmed death-1), PD-L1 (programmed death-ligand 1) and PD-L2 (programmed death-ligand 2) are among the inhibitory immune mediators on the PD-1 pathway. However, previous data regarding the association between MD and PD-1 pathway were still scarce; therefore, we investigated the association of PD-1 pathway with MD. METHODS: During a period of 2 years, patients with MD and healthy controls were recruited from a medical centre in this study. The diagnosis of MD was established according to the DSM-5 criteria. The severity of MD was assessed with 17-item Hamilton Depression Rating Scale. PD-1, PD-L1 and PD-L2 were detected in peripheral blood from MD patients after 4 weeks of treatment with antidepressant drugs. RESULTS: A total of 54 patients with MD and 38 healthy controls were recruited. According to the analyses, there is a significantly higher PD-L2 level in MD than in healthy controls and lower PD-1 level after age and BMI adjustment. Besides, moderately positive correlation between HAM-D scores and PD-L2 level was found. CONCLUSIONS: It was found that PD-1 pathway might play an important role in MD. We need a large sample to prove these results in the future.

Serum protein levels of brain-derived neurotrophic factor and tropomyosin-related kinase B in bipolar disorder: effects of mood stabilizers.

AIM: In this study, we investigated serum protein levels of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in patients with bipolar disorder. METHODS: Over a 2-year period, 26 patients with bipolar I disorder (manic episode) and 56 healthy controls were recruited. The Young Mania Rating Scale scores of patients with bipolar mania were >26. Serum BDNF and TrkB protein levels were measured with ELISA kits. RESULTS: Using ANCOVA with age adjustment, we found that there were no significant differences in serum BDNF protein levels between patients with bipolar mania and healthy controls (p = 0.582). In contrast, the serum TrkB protein level was significantly higher in bipolar mania patients than in healthy controls (p = 0.001), especially in women (p = 0.001). Of 26 patients with bipolar mania, 21 underwent a second measurement of serum BDNF and TrkB protein levels after a 4-week treatment with mood stabilizers. There were no significant changes in serum BDNF or TrkB protein levels. CONCLUSION: These findings suggest that serum TrkB protein levels may play an important role in the psychopathology of bipolar mania. However, a larger sample size is needed to confirm these results.

Orexin/hypocretin and major psychiatric disorders.

Orexin A and B, also known as hypocretin 1 and 2, are excitory neuropeptides synthesized in the perifornical and lateral hypothalamic areas. Following their discovery in 1998, orexins are now known to be involved in feeding, sleep, stress response, and reward processing. Most importantly, orexin deficiency has been linked to narcolepsy, a neurological sleep-wake disorder. Patients with narcolepsy also present overlapping symptoms with psychiatric disorders, such as anxiety and depressed mood, and even hallucinations, which often lead to misdiagnosis in the initial assessment. In this article, we aim to review studies of the orexin system associated with the three major psychiatric disorders: schizophrenia, major depressive disorder (MDD), and bipolar disorder. In addition to animal and clinical reports, studies of the orexin system in treatment, symptoms and side effects would also be reviewed. Thus far, relatively robust evidence suggests a connection of the orexin system with MDD. Findings of orexin involvement in schizophrenia are inconsistent and only studies in bipolar disorder are limited. While the orexin system might not be firmly associated with diagnosis, it may be useful to target specific symptom within the diagnosis or treatment, such as insomnia, weight gain and polydipsia.

Isobaric Tags for Relative and Absolute Quantitation Identification of Blood Proteins Relevant to Paroxetine Response in Patients With Major Depressive Disorder.

Objectives: Isobaric tags for relative and absolute quantitation (iTRAQ) is a proteomic investigation that could be utilized for rapid identification and quantification of proteins, which we would use to identify differentially expressed proteins in treatment responsive patients with major depressive disorder (MDD). Methods: Six treatment responsive patients of MDD were recruited, and their peripheral blood mononuclear cell (PBMC) were collected before and after 4 weeks of paroxetine treatment. iTRAQ and Mascot search engine were used to detect differentially expressed proteins, which were then validated by Western blot. Results: Two thousand one hundred and fifty three proteins were screened, and seven proteins showed differences of more than two-fold and 62 proteins with a differences of less than two-fold. Six proteins with commercially available antibodies were identified, and were validated by Western blot in 10 paroxetine responsive MDD patients. Putative hydroxypyruvate isomerase (HYI), eukaryotic translation initiation factor 4H (eIF4H), and RNA binding motif 8A (RBM8A) had statistically significant differences before and after treatment in the validation. Data are available via ProteomeXchange with identifier PXD028947. Conclusions: By using iTRAQ and Western blot, we were able to identify HYI, eIF4H, and RAM8a to be the potential predictors of paroxetine treatment response in patients with MDD. This finding could help establish future individualized medicine.

Corrigendum: Isobaric Tags for Relative and Absolute Quantitation Identification of Blood Proteins Relevant to Paroxetine Response in Patients With Major Depressive Disorder.

[This corrects the article DOI: 10.3389/fpsyt.2022.577857.].

Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia: A Systematic Review and Network Meta-analysis.

Importance: Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear. Objective: To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms. Data Sources: The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021. Study Selection: A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model. Main Outcomes and Measures: The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms. Results: Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups. Conclusions and Relevance: In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted.

Effects of antipsychotics on the serum BDNF levels in schizophrenia.

Brain-derived neurotrophic factor (BDNF) is active during a critical developmental period and likely influences the neuroplasticity of schizophrenia. This study longitudinally examined the effects of atypical antipsychotics on serum BDNF levels in schizophrenic patients. Specifically, this study measured serum BDNF levels in 53 patients with paranoid schizophrenia during a relapse and again 4 weeks following the administration of antipsychotic treatment (with risperidone in 32 cases, and clozapine in 21 cases). BDNF levels remained unchanged relative to study entry after 4 weeks of atypical antipsychotic treatment. However, serum BDNF was significantly increased in the subgroup receiving risperidone compared to that receiving clozapine, albeit only in the 15 male subjects and not in the 17 females. These results suggest that gender might significantly influence the antipsychotic treatment of schizophrenia from the perspective of BDNF. These findings may also indicate that the treatment with atypical antipsychotic agents differentially affects BDNF levels.