Clinical characteristics of 217 Chinese cases with depersonalization/derealization disorder.

Depersonalization/derealization disorder (DPD) is a prevalent yet inadequately understood clinical condition characterized by a recurrent or persistent sense of unreality. This study aims to provide insight into DPD through descriptive and comparative analyses involving a large group of Chinese participants. The socio-demographic details (age, gender proportion, education, occupational status, marital status), depersonalized and dissociative symptom characteristics (symptomatic factors or subscales of the Cambridge Depersonalization Scale and the Dissociative Experiences Scale), development trajectory (age of onset, potential precipitating factors, course characteristics), treatment history (duration of delayed healthcare attendance, duration of delayed diagnosis, previous diagnoses), and adverse childhood experiences of the DPD patients are presented. Comparisons of anxiety and depressive symptoms, alongside psychosocial functioning, between DPD participants and those diagnosed with generalized anxiety disorder, bipolar disorders, and major depressive disorder were conducted. The analysis highlights a higher male preponderance and early onset of DPD, symptomatology marked by derealization, notable impairment in psychosocial functioning, and prolonged periods of delayed healthcare attendance and diagnosis associated with symptom severity. Furthermore, noteworthy relationships between adverse childhood experiences and symptom levels were identified. The findings substantiate the view that DPD is a serious but neglected mental disorder, urging initiatives to improve the current condition of DPD patients.

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.

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.

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.

Shi-Zhen-An-Shen Decoction, a Herbal Medicine That Reverses Cuprizone-Induced Demyelination and Behavioral Deficits in Mice Independent of the Neuregulin-1 Pathway.

Shi-Zhen-An-Shen decoction (SZASD), a Chinese herbal medicine that is a liquor extracted from plants by boiling, has been reported to be effective in treating schizophrenia. However, the mechanism is unclear. Abnormal demyelination has been implicated in schizophrenia. The aim of this study was to investigate the effect of SZASD on myelin in demyelinated mice exhibiting schizophrenia-like behaviors. Sixty male C57BL/6 mice were randomly divided into six groups (n = 10 per group): (1) control group, (2) cuprizone (CPZ, a copper chelator that induced demyelination, 0.2% w/w)+saline, (3) CPZ+low-dose SZASD (8.65 g·kg-1·d-1), (4) CPZ+medium-dose SZASD (17.29 g·kg-1·d-1), (5) CPZ+high-dose SZASD (25.94 g·kg-1·d-1), and (6) CPZ+quetiapine (QTP, an atypical antipsychotic that served as a positive treatment control, 10 mg·kg-1·d-1). Mice in groups 2-6 were treated with CPZ added to rodent chow for six weeks to induce demyelination. During the last two weeks, these mice were given an oral gavage of sterile saline, SZASD, or quetiapine. Behavioral tests and brain analyses were conducted after the last treatment. The brain expression of myelin basic protein (MBP) and neuregulin-1 (NRG-1) was assessed using immunohistochemistry and Western blots. CPZ induced significant schizophrenia-like behaviors in the mice, including reduced nest-building activity and sensory gating deficits. Hyperlocomotor activity was accompanied by significant reductions in MBP expression in the corpus callosum, hippocampus, and cerebral cortex. However, both QTP and SZASD significantly reversed the schizophrenia-like behaviors and demyelination in CPZ-fed mice. The QTP and medium-dose SZASD resulted in better therapeutic effects compared to the low and high SZASD doses. Reduced NRG-1 expression was observed in CPZ-fed mice compared with controls, but neither QTP nor SZASD showed significant influence on NRG-1 expression in the hippocampus. Together, SZASD showed a therapeutic effect on demyelinated mice, and the improvement of demyelination might not be through the NRG-1 pathway.

Disruptions of frontoparietal control network and default mode network linking the metacognitive deficits with clinical symptoms in schizophrenia.

The metacognitive deficit in awareness of one's own mental states is a core feature of schizophrenia (SZ). The previous studies suggested that the metacognitive deficit associates with clinical symptoms. However, the neural mechanisms underlying the relationship remain largely unknown. We here investigated the neural activities associated with the metacognitive deficit and the neural signatures associated with clinical symptoms in 38 patients with SZ using functional magnetic resonance imaging with a perceptual decision-making task accompanied with metacognition, in comparison to 38 age, gender, and education matched healthy control subjects. The metacognitive deficit in patients with SZ was associated with reduced regional activity in both the frontoparietal control network (FPCN) and the default mode network. Critically, the anticorrelational balance between the two disrupted networks was substantially altered during metacognition, and the extent of alteration positively scaled with negative symptoms. Conversely, decoupling between the two networks was impaired when metacognitive monitoring was not required, and the strength of excessive neural activity positively scaled with positive symptoms. Thus, disruptions of the FPCN and the default mode network underlie the metacognitive deficit, and alternations of network balance between the two networks correlate with clinical symptoms in SZ. These findings implicate that rebalancing these networks holds important clinical potential in developing more efficacious therapeutic treatments.

Deficits of subliminal self-face processing in schizophrenia.

Most studies show that self-processing in schizophrenia is impaired at the supraliminal level. Schizophrenic patients generally lack the ability to prioritize the processing of self-related information, such as their own face. However, some evidence suggests that schizophrenic patients may retain intact subliminal processing abilities even though their conscious experiences are compromised. We conducted the first study exploring schizophrenic patients' subliminal self-face processing. Using a breaking continuous flash suppression (bCFS) paradigm, we interocularly suppressed face images (self, famous, and unknown faces). Participants' reaction times to detect the faces when they broke the suppression were recorded as an index for the subliminal processing of faces. Unlike the healthy controls, schizophrenic patients did not demonstrate a processing advantage for their own face when it broke interocular suppression; only a face familiarity effect was found. These findings contribute to the understanding of self-processing deficits in schizophrenia.

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.

Altered Functional Connectivity of the Thalamus Subregions Associated with Impaired Attention After Sleep Deprivation.

Objective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD. Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects. Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the "somatosensory" thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and "somatosensory" thalamic seed was negatively associated with the change in orienting effect of the participants. Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.

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.

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.

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.

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.

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.

[Case constitution and medication intention of bipolar disordered outpatients at two grade IIIa hospitals in Beijing].

OBJECTIVE: To acquire the case constitution of bipolar disordered (BPD) in mood disordered (MD) outpatients at two local Beijing hospitals to understand the case constitution and medication intention of clinical psychiatrists in terms of differentiation and treatment of BPD. METHODS: All psychiatrists at Anding Hospital and neurological physicians at Xuanwu Hospital were surveyed by self-rated questionnaires and the analysis focused on the composition of proportions of BPD cases out of MD patients. The items included estimated ratio of BPD cases, doctors' intention of drug prescription and clinical therapeutic regimen for treatment of BPD. RESULTS: (1) BPD ratio in MD outpatients of two hospitals were 41.79% and 12.24% respectively; (2) Doctor's ratio who estimated BPD ratio in MD cases < 40% were 60% and 100% respectively; (3) 100% psychiatrists at Beijing Anding Hospital and 72.22% neurological physicians at Beijing Xuanwu Hospital prescribed antidepressant to BPD cases; (4) Doctor's ratio who adopted therapeutic schedule of 'antidepressant + mood stabilizer' or 'antidepressant + mood stabilizer + antipsychotic' agents for BPD were 100% and 66.67% respectively. CONCLUSION: Regardless of mental specialized hospital or general hospital, the physicians should pay great attention to the differentiation of BPD and the rationality of drug prescription.

[Treatment of refractory depression patients of yin deficiency inner heat syndrome by jieyu granule combined paroxetine: an efficacy observation].

OBJECTIVE: To explore the efficacy of jieyu granule (JG) combined Paroxetine in treating refractory depression (RD) patients of yin deficiency inner heat syndrome (YDIHS). METHODS: Seventy RD patients of YDIHS were randomly assigned to the experimental group (JG combined Paroxetine) and the control group (Chinese medical placebo combined Paroxetine), 35 cases in each group. Hamilt Depression Rating Scale and Hamilton Anxiety Scale were used before treatment, and at the weekend of the 2nd, 4th, and 8th week, respectively. RESULTS: In the experimental group, 32 patients completed the trial and 3 patients dropped out. In the control group, 33 patients completed the trial and 2 patients dropped out. At the end of the 8th week of the treatment, the total score of Hamilt Depression Rating Scale was (14.75 +/- 7.85) in the experimental group, lower than that of the control group (19. 06 +/- 8. 31, P <0.05). At the end of the 2nd, 4th, and 8th week of the treatment, the score of Hamilton Anxiety Scale was 17.03 +/- 4.25, 14.50 +/- 5. 13, and 11.03 +/- 4.88, respectively in the experimental group, lower than that of the control group at each corresponding time point (19. 60 +/-3. 96, 17. 12 +/- 4.14, 14.64 +/- 4.47, P <0.05, P <0.01). CONCLUSION: The efficacy of JG combined Paroxetine for treating RD patients of YDIHS was superior to that of using Paroxetine alone.

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.

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.

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.

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.