How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity.

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

The role of the immune system in depersonalisation disorder.

OBJECTIVES: Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. METHODS: We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. RESULTS: We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. CONCLUSIONS: The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD.

Abnormalities in motor adaptation to different types of perturbations in schizophreniaperturbations in schizophrenia.

Schizophrenia is a mental health disorder that often includes psychomotor disturbances, impacting how individuals adjust their motor output based on the cause of motor errors. While previous motor adaptation studies on individuals with schizophrenia have largely focused on large and consistent perturbations induced by abrupt experimental manipulations, such as donning prism goggles, the adaptation process to random perturbations, either caused by intrinsic motor noise or external disturbances, has not been examined - despite its ecological relevance. Here, we used a unified behavioral task paradigm to examine motor adaptation to perturbations of three causal structures among individuals in the remission stage of schizophrenia, youth with ultra-high risk of psychosis, adults with active symptoms, and age-matched controls. Results showed that individuals with schizophrenia had reduced trial-by-trial adaptation and large error variance when adapting to their own motor noise. When adapting to random but salient perturbations, they showed intact adaptation and normal causal inference of errors. This contrasted with reduced adaptation to large yet consistent perturbations, which could reflect difficulties in forming cognitive strategies rather than the often-assumed impairments in procedural learning or sense of agency. Furthermore, the observed adaptation effects were correlated with the severity of positive symptoms across the diagnosis groups. Our findings suggest that individuals with schizophrenia face challenges in accommodating intrinsic perturbations when motor errors are ambiguous but adapt with intact causal attribution when errors are salient.

Effects of aripiprazole on resting-state functional connectivity of large-scale brain networks in first-episode drug-naïve schizophrenia patients.

Aripiprazole modulates functional connectivity (FC) between several brain regions in first-episode schizophrenia patients, contributing to improvement in clinical symptoms. However, the effects of aripiprazole on abnormal connections among extensive brain networks in schizophrenia patients remain unclear. We aimed to investigate the effects of 12 weeks of aripiprazole treatment on the FC of large-scale brain networks. Forty-five first-episode drug-naïve schizophrenia patients and 45 healthy controls were recruited for this longitudinal study. Resting-state functional magnetic resonance imaging (fMRI) data were collected at baseline and after 12 weeks of aripiprazole treatment. The patients were classified into those in response (SCHr group) and non-response (SCHnr group) according to the improvement of clinical symptoms after 12-weeks treatment. The FC were evaluated for seven large-scale brain networks. In addition, correlation analysis was performed to investigate associations between changes FC of large-scale brain networks and clinical symptoms. Before aripiprazole treatment, schizophrenia patients showed decreased FC of extensive brain networks compared to healthy controls. The 12-week aripiprazole treatment significantly prevented the constantly decreased FC of subcortical network, default mode network and other brain networks in patients with SCHr, in association with the improvement of clinical symptoms. Taken together, these findings have revealed the effects of aripiprazole on FC in large-scale networks in schizophrenia patients, which could provide new insight on interpreting symptom improvement in SCH.

Effects of Ziprasidone or Haloperidol on Theory of Mind in Patients With Schizophrenia: A 16-week Pilot Trial.

OBJECTIVES: Schizophrenia is associated with impairment in theory of mind (ToM), which is defined as the ability to make judgments about mental states and is related to medial prefrontal cortical activity. Ziprasidone, but not haloperidol, is known to have a protective effect in the medial prefrontal cortex. Thus, we hypothesized that these 2 drugs would have different efficacy in improving ToM task performance in patients with schizophrenia. METHODS: Patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia matched for sex, duration of illness, and education were randomized to receive ziprasidone (n=30) or haloperidol (n=30). All patients were assessed using the Positive and Negative Syndrome Scale and the Personal and Social Functioning Scale. ToM was assessed using a first-order false belief task, a second-order false belief task, the faux-pas task, and the Reading the Mind in the Eyes Task, in order of developmental complexity and difficulty. The primary outcome was change in ToM performance from baseline to 16 weeks of treatment. RESULTS: For the first-order false belief task, there were no significant differences between the groups (P>0.05). For the second-order false belief task, the interaction effect was significant (P<0.05), and the simple effect of time showed a significant difference only in the ziprasidone group (P<0.001). For the faux-pas task, the interaction effect was not significant (P>0.05). For the Reading the Mind in the Eyes Task, the interaction effect was significant (P<0.05), and the simple effect of time showed a significant difference only in the ziprasidone group (P<0.001). The Positive and Negative Syndrome Scale results were similar between the groups. The ziprasidone group performed better than the haloperidol group on the Personal and Social Functioning Scale. There were no major safety concerns or adverse events. CONCLUSIONS: The findings of this study suggest that ziprasidone could improve ToM and might be superior to haloperidol for improving complex ToM as well as personal and social functioning in patients with schizophrenia. TRIAL REGISTRATION CHINESE CLINICAL TRIAL REGISTER: ChiCTR2200060542.

Serum proteomics analysis of drug-naïve patients with generalised anxiety disorder: Tandem mass tags and multiple reaction monitoring.

OBJECTIVES: The prevalence of generalised anxiety disorder (GAD) is high. However, the underlying mechanisms remain elusive. Proteomics techniques can be employed to assess the pathological mechanisms involved in GAD. METHODS: Twenty-two drug-naive GAD patients were recruited, their serum samples were used for protein quantification and identified using Tandem Mass Tag and Multiple Reaction Monitoring (MRM). Machine learning models were employed to construct predictive models for disease occurrence by using clinical scores and target proteins as input variables. RESULTS: A total of 991 proteins were differentially expressed between GAD and healthy participants. Gene Ontology analysis revealed that these proteins were significantly associated with stress response and biological regulation, suggesting a significant implication in anxiety disorders. MRM validation revealed evident disparities in 12 specific proteins. The machine learning model found a set of five proteins accurately predicting the occurrence of the disease at a rate of 87.5%, such as alpha 1B-glycoprotein, complement component 4 A, transferrin, V3-3, and defensin alpha 1. These proteins had a functional association with immune inflammation. CONCLUSIONS: The development of generalised anxiety disorder might be closely linked to the immune inflammatory stress response.

The Treatment of Depersonalization-Derealization Disorder: A Systematic Review.

Depersonalization-derealization disorder (DPD) is characterized by persistent or recurrent experiences of detachment from oneself and surroundings, as well as a sense of unreality. Considering the inadequacy of current research on treatment, we performed a systematic review of the available pharmacotherapies, neuromodulations, and psychotherapies for DPD. The systematic review protocol was based on PRISMA 2020 guidelines and pre-registered. The PubMed, Web of Science, PsycINFO, Embase, the Cochrane Library, Scopus, and ScienceDirect databases were searched from inception to June 2021. All treatments for DPD and all study types, including controlled and observational studies as well as case reports, were assessed. Of the identified 17,540 studies, 41 studies (four randomized controlled trials, one non-randomized controlled trial, 10 case series, and 26 case reports) involving 300 participants met the eligibility criteria. We identified 30 methods that have been applied independently or in combination to treat DPD since 1955. The quality of these studies was considered. The relationship between individual differences, such as symptoms, comorbidities, history, and duration since onset, and treatment effects was explored. The results suggest that a series of treatments, such as pharmacotherapies, neuromodulation, and psychotherapies, could be considered in combination. However, the quality and quantity of studies were generally low considering the high prevalence of DPD. The review concludes with suggestions for future research and an urgent call for more high-quality research.

Altered Functional Connectivity in Working Memory Network After Acute Sleep Deprivation.

Acute sleep deprivation (SD) has a detrimental effect on working memory (WM). However, prior functional magnetic resonance imaging (fMRI) studies have failed to reach consistent results on brain functions underlying WM decline after acute SD. Thus, we aimed to identify convergent patterns of abnormal brain functions due to WM decline after acute SD. A coordinate-based activation likelihood estimation (ALE) meta-analysis of task-state fMRI studies testing the effects of acute SD on WM was performed to construct WM network. Then 26 healthy subjects with regular sleep performed the n-back task and underwent resting-state fMRI scanning before and after 24 h of SD. The functional connectivity (FC) among these brain regions and correlations with WM performance were calculated. The ALE results displayed that SD subjects performing WM-related tasks had consistent hypoactivation in the occipital lobe, left middle occipital gyrus, parietal lobe, precuneus, inferior parietal lobule, right sub-gyral, right cuneus, right limbic lobe, and right posterior cingulate. Consistent hyperactivation was showed in the left cerebrum, including the lingual gyrus, posterior lobe, cuneus, temporal lobe, and fusiform gyrus. These identified brain regions as the seeds to construct WM network. The increased FC between the left declive and right sub-gyral, left cuneus and left lingual gyrus, and left cuneus and right post cingulate were found. Furthermore, the impaired WM performance negatively correlated with increased FC. Taken together, our findings highlight that the altered FC in WM network may be the underlying mechanisms of WM decline after acute SD.

Altered Functional Connectivity of Large-Scale Brain Networks in Psychogenic Erectile Dysfunction Associated with Cognitive Impairments.

Purpose: Several studies have demonstrated that psychogenic erectile dysfunction (pED) patients potentially suffer from cognitive dysfunction. Despite that previous neuroimaging studies have reported abnormal functional connections of brain areas associated with cognitive function in pED, the underlying mechanisms of cognitive dysfunction in pED remain elusive. This study aims to investigate the underlying mechanisms of cognitive dysfunction by analyzing large-scale brain networks. Patients and Methods: A total of 30 patients with pED and 30 matched healthy controls (HCs) were recruited in this study and scanned by resting-state functional magnetic resonance imaging. The Dosenbach Atlas was used to define large-scale networks across the brain. The resting-state functional connectivity (FC) within and between large-scale brain networks was calculated to compare pED patients with HCs. The relationship among cognitive performances and altered FC of large-scale brain networks was further explored in pED patients. Results: Our results showed that the decreased FC within visual network, and between visual network and default mode network, visual network and frontoparietal network, and ventral attention and default mode network were found in pED patients. Furthermore, there was a positive correlation between immediate memory score and FC within visual network. The visuospatial score was negatively correlated with decreased FC between ventral attention network and default mode network. Conclusion: Taken together, our findings revealed the relationship between cognitive impairments and altered FC between large-scale brain networks in pED patients, providing the new evidence about the neural mechanisms of cognitive dysfunction in pED patients.

Altered White Matter Structural Network Connectivity Associated with Cognitive Declines in Psychogenic Erectile Dysfunction.

It has been reported that individuals with psychogenic erectile dysfunction (pED) potentially suffer from cognitive declines. Despite that increasing neuroimaging studies have demonstrated abnormalities of cerebral structural changes in pED, the association between altered white matter (WM) structural network and cognitive impairments remains unclear. Hence, this study aimed to explore the relationship between WM structural network connectivity and cognitive performance in patients with pED. Forty pED patients and 33 healthy controls (HCs) were recruited to perform cognitive assessments, and diffusion tensor imaging scans. We firstly constructed the WM structural network and applied the machine learning method to identify the important features. Then, we examined group differences in cognitive assessments, WM structural network connectivity within the identified features, and associations between altered WM structural network connectivity and cognitive scores in pED patients. From 26,896 features of DTI data, 24 important features were identified by K-Nearest Neighbor classification with a satisfactory accuracy (78%). Compared with HCs, we found that pED patients showed higher fractional anisotropy (FA) values between left transverse temporal sulcus and left supramarginal gyrus, and lower FA values between left suborbital sulcus and left para-hippocampal part of the medial occipito-temporal gyrus in pED patients. Furthermore, the increased FA between left transverse temporal sulcus and left supramarginal gyrus was observed to be negatively associated with impaired delayed memory. Overall, our findings provide new insights into WM network alterations associated with impaired cognitive functions in pED, which may unravel the potential neural mechanisms underlying the cognitive impairments of pED patients.

Altered functional connectivity after acute sleep deprivation reveals potential locations for noninvasive brain stimulation techniques.

BACKGROUNDS: Non-invasive brain stimulation (NIBS) techniques are emerging as efficacious treatments for sleep deprivation (SD). However, the stimulation location of NIBS (e.g. transcranial magnetic stimulation and transcranial direct current stimulation) on intervening acute SD is limited in previous studies. In this study, we aimed to investigate potentially effective targets of NIBS on intervening acute SD. METHODS: We firstly performed a meta-analysis of 95 functional magnetic resonance imaging studies to find SD-related brain regions as regions of interest (ROI). Subsequently, we used resting-state functional connectivity analysis in 32 young individuals suffering from 24 h SD to identify brain surface regions associated with the ROIs. Finally, we applied 10-20 system coordinates to locate scalp sites for NIBS corresponding to the brain surface regions. RESULTS: We identified the bilateral dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, left supplementary motor area, precentral, right precuneus, bilateral inferior parietal gyrus, right middle temporal gyrus, and superior frontal gyrus as potential targets of NIBS for intervening SD. The 10-20 system coordinates corresponding to these brain surface regions were identified as potential sites for NIBS. CONCLUSIONS: In conclusion, we identified several potential targets which could provide alternative stimulation locations for the use of NIBS on young patients suffering from acute SD.

Preventive interventions for individuals at risk of developing bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to explore whether early interventions can reduce affective symptoms and have long-term benefits among individuals at risk of bipolar disorder (BD). METHODS: The PubMed, Embase, and Web of Science databases were searched. The primary outcome was continuous symptom scores before and after treatment. Random effects meta-analyses were conducted for each outcome arm studied and pooled mean difference estimates were calculated. RESULTS: The search identified 10 controlled studies involving 425 participants and 6 single-arm studies involving 90 participants. For controlled trials, meta-analysis showed that the interventions led to greater reduction in clinical global score than placebo (standardized mean differences (SMD) = -0.96, 95 % CI:-1.32, -0.60), and supported a long-term longitudinal effect for pharmacotherapy (SMD = -0.42, 95 % CI: -0.79, -0.05). For single-arm trials, both pharmacotherapy and psychotherapy showed efficacy for depressive symptoms, while pharmacotherapy only showed efficacy for hypomania symptoms (effect size (ES) = -9.16, 95 % CI:-11.29, -7.04). Discontinuation of pharmacotherapy due to adverse effects did not show a difference. LIMITATIONS: The primary limitations are the small number of RCTs and the influence of medication dosage. CONCLUSIONS: Based on the limited available data, early interventions show efficacy for individuals at risk of BD. Psychological therapy might be more beneficial for depressive symptoms and have long-term benefits for hypomania. Pharmacotherapy may be appropriate in situations of severe hypomanic symptoms and the poor functioning. Large, well-designed, double-blind -controlled trials are needed to make solid conclusions about the efficacy of early interventions.

Effect of Shi-Zhen-An-Shen herbal formula granule in the treatment of young people at ultra-high risk for psychosis: a pilot study.

Introduction: To date, there is no conclusive evidence for early interventions on ultra-high risk (UHR) for psychosis. The Chinese herbal medicine is confirmed to be beneficial in improving psychiatric symptoms and cognitive impairments for schizophrenia patients. However, the effect of Chinese herbal medicine on treating UHR patients remains unknown. Methods: Eighty UHR patients were recruited from the outpatient department. They were randomly assigned to receive either Shi-Zhen-An-Shen herbal formula granule (SZAS-HFG) combined with aripiprazole placebo or aripiprazole combined with SZAS-HFG placebo for a 12-week treatment. The psychiatric symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). The Trail Making Test part A (TMT-A), Brief Visuospatial Memory Test (BVMT), Hopkins Verbal Learning Test (HVLT), and Continuous Performance Test (CPT) were used to assess cognitive functions. we also employed the Global Assessment of Functioning (GAF) to evaluate social functioning. The linear mixed-effects models were performed to detect the difference in effectiveness between the two groups. Results: After 12-week treatment, both groups showed significant effects of time on SIPS, TMT-A, HVLT, BVMT, and GAF. There was a significant effect of group only on CPT. Moreover, we also found a significant interaction effect on GAF. Conclusion: SZAS-HFG can effectively alleviate psychosis symptoms, and improve cognitive impairments and overall functioning as well as aripiprazole.Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR-IOR-17013513.

Metabolic changes in patients with bipolar disorder in spring.

Bipolar disorder (BD) is a common mental condition with a seasonal pattern (SP) of onset. In the spring, there is a higher incidence rate of mania or mixed onset and suicide. However, the underlying mechanism of this SP remains unclear. In this study, targeted metabolomics was used to understand metabolic changes in patients with BD before and after the spring equinox. Nine patients with BD and matched healthy controls were tested for serum metabolomics at the spring equinox and 15 days before and after the spring equinox. The results showed that 27 metabolite levels changed significantly, three of which interacted between three time points and groups involving triglyceride (TG, 20:4_34:2), TG (20:4_34:3) and TG (16:0_36:6). The identified metabolic pathways mainly involved arginine biosynthesis, D-glutamine and D-glutamate metabolism, and nitrogen metabolism. Changes in solar radiation and lunar cycle during spring may be the external causes of metabolic changes. These findings help to further explore seasonal metabolic changes in patients with BD and provide insights into the mechanisms of patients' emotional changes in spring.

Variation in self and familiar facial recognition in bipolar disorder patients at different clinical stages.

Previous studies suggest a close relationship between self-disorders and schizophrenia or unipolar depression. However, few studies have explored the characteristics of self-processing in bipolar disorder (BD) during different clinical states. This study compared the differences in self-face recognition (SFR) among patients with bipolar mania (BPM), bipolar depression (BPD), bipolar remission (RM), and healthy controls (HC). Images of subject's own face, a familiar face, and an unfamiliar face were combined in pairs at a certain proportion to obtain three types of blended images. We then compared the tendency between BD and HC while judging two kinds of blended faces emerging from presentation software. The results showed that the BPM and BPD groups seemed to lack an advantage in self-recognition. Self-processing and familiarity processing were significantly enhanced in BPM patients, while only familiarity processing was enhanced in BPD. The severity of clinical symptoms was not significantly correlated with self-bias or familiarity bias in BD.

Cyclothymic Temperament, Physical Neglect, and Earlier Age of Onset Predict Poor Medication Adherence in Patients With Bipolar Disorder.

ABSTRACT: Individual-level risk factors may predict poor medication adherence (PMA) in bipolar disorder (BD). This study aimed to evaluate the association between affective temperament, childhood trauma, age of first onset, and PMA in patients with BD in China. A total of 168 patients completed the eight-item Morisky Medication Adherence Scale; the Short Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire; and the Childhood Trauma Questionnaire-Short Form. Scores were then compared between PMA and non-PMA groups. Binary logistic regression showed that age of first onset was negatively correlated with PMA ( ß = -0.106, p = 0.002), whereas physical neglect and cyclothymic temperament were positively correlated with PMA ( ß = 0.143, p = 0.029; ß = 0.19, p = 0.001, respectively). These findings indicate that cyclothymic temperament, physical neglect, and earlier onset are predictors of PMA in patients with BD and that such patients may require further attention to improve medical compliance.

An Experimental Study of Subliminal Self-Face Processing in Depersonalization-Derealization Disorder.

The self-perception or self-experience of patients with depersonalization/derealization disorder (DPD) is altered, leading to a profound disruption in self-awareness. The main aim of the study is to explore the characteristics of subliminal self-face processing in DPD patients. To our knowledge, this is the first experimental study that has measured and evaluated subliminal self-processing in DPD. To better understand this, we examined the ability of patients with DPD and healthy controls (HC) to identify pictures of faces using an experimental paradigm of breaking continuous flash suppression. There were 23 DPD outpatients from Beijing Anding Hospital, Capital Medical University and 23 matched HC who participated in this experiment. The time needed for a face to break into awareness was taken as the measure of participants' subliminal processing of that face. The results indicated that there were significant differences between the DPD patients and HC in subliminal reaction times to different faces. Under experimental conditions, the average reaction response of self-face recognition in the HC group was significantly faster than for a famous face. However, this difference was not observed in DPD patients, which means that DPD patients did not show the processing advantage of their own faces as did the HC. The results suggest a deficit in subliminal self-face processing in DPD.

Altered functional connectivity of cerebellar networks in first-episode schizophrenia.

Introduction: Abnormalities of the cerebellum have been displayed to be a manifestation of schizophrenia (SCH) which is a detrimental psychiatric disorder. It has been recognized that the cerebellum contributes to motor function, sensorimotor function, cognition, and other brain functions in association with cerebral functions. Multiple studies have observed that abnormal alterations in cerebro-cerebellar functional connectivity (FC) were shown in patients with SCH. However, the FC of cerebellar networks in SCH remains unclear. Methods: In this study, we explored the FC of cerebellar networks of 45 patients with first-episode SCH and 45 healthy control (HC) subjects by using a defined Yeo 17 network parcellation system. Furthermore, we performed a correlation analysis between cerebellar networks' FC and positive and negative symptoms in patients with first-episode SCH. Finally, we established the classification model to provide relatively suitable features for patients with first-episode SCH concerning the cerebellar networks. Results: We found lower between-network FCs between 14 distinct cerebellar network pairs in patients with first-episode SCH, compared to the HCs. Significantly, the between-network FC in N2-N15 was positively associated with positive symptom severity; meanwhile, N4-N15 was negatively associated with negative symptom severity. Besides, our results revealed a satisfactory classification accuracy (79%) of these decreased between-network FCs of cerebellar networks for correctly identifying patients with first-episode SCH. Conclusion: Conclusively, between-network abnormalities in the cerebellum are closely related to positive and negative symptoms of patients with first-episode SCH. In addition, the classification results suggest that the cerebellar networks can be a potential target for further elucidating the underlying mechanisms in first-episode SCH.

Protective Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment in MK801-Induced Schizophrenia Model.

BACKGROUND: Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. METHODS: Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. RESULTS: Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. CONCLUSIONS: Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.

Potential Targets for Noninvasive Brain Stimulation on Depersonalization-Derealization Disorder.

INTRODUCTION: Non-invasive brain stimulation seems to be beneficial for DPD patients. However, the sites used in previous studies were empirical. Exploring new stimulation locations via functional magnetic resonance imaging may improve the efficacy. OBJECTIVES: The objective was to find potential locations for non-invasive brain stimulation on the depersonalization-derealization disorder. METHODS: We explored the potential brain surface regions from three pipelines: pipeline 1: activation likelihood estimation meta-analysis (five studies with 36 foci included); pipeline 2: functional connectivity analysis based on DPD-network (76 subjects included); and pipeline 3: functional connectivity analysis based on DPD regions of interest from the meta-analysis. Potential targets were the 10-20 system coordinates for brain surface regions. RESULTS: We identified several potential brain surface regions, including the bilateral medial prefrontal cortex, dorsal lateral prefrontal cortex, superior parietal gyrus, superior temporal gyrus, and right ventrolateral prefrontal cortex as potential sites. CONCLUSION: Our findings of the potential stimulation targets might help clinicians optimize the application of non-invasive brain stimulation therapy in individuals with DPD.