Background: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. Methods: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. Results: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 ( P _Bonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 ( P _Bonferroni < 0.001). Amisulpride group had a higher treatment response rate ( P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group ( P _Bonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. Conclusion: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974

Background and Hypothesis: Psychiatric comorbidities suggest that symptoms overlap across different diagnoses; the transdiagnostic network approach is valuable for studying psychopathology. Childhood trauma is a common transdiagnostic risk factor for psychiatric disorders, but the complex relationship between childhood trauma and psychopathology has seldom been investigated using a large cross-sectional transdiagnostic sample. Study Design: This study recruited 869 patients with different diagnoses, including 418 schizophrenia, 215 bipolar disorder, and 236 major depressive disorder. Participants completed psychiatric interviews and self-report questionnaires. We constructed dimension- and item-level Least Absolute Shrinkage and Selection Operator-based (LASSO) networks to explore the relationship between childhood trauma, psychopathology, and duration of illness. Moreover, we constructed directed acyclic graphs (DAGs) to tentatively clarify the potential directions of associations among these variables. Network Comparison Tests (NCTs) were conducted for different diagnostic groups and gender-stratified groups. Study Results: The transdiagnostic LASSO networks showed that different types of childhood trauma exerted distinct impacts on various psychopathological dimensions. Emotional abuse was linked to depressive symptoms, physical abuse to excited symptoms, sexual abuse to positive and disorganized symptoms, emotional neglect to depressive symptoms and motivation and pleasure (MAP) deficits factor of negative symptoms, and physical neglect to MAP factor. The DAG findings generally concurred with the LASSO network. The NCT showed comparable networks. Conclusions: Our findings suggest that childhood trauma is significantly associated with the development of psychopathology across different diagnostic groups. The affective pathway model suggests that early identification and tailored interventions would be needed for people with a history of childhood trauma.

Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population. A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use. The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001). The cross-sectional design of this study precludes establishing causal relationships. Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD.

This study aims to compare the differences in clinical features and inflammatory factors between unipolar depression and bipolar depression, and to investigate potential clinical characteristics and peripheral blood biomarkers that could be used to differentiate between these two conditions. Furthermore, the study seeks to establish a predictive model. Inpatients from the Shanghai Mental Health Center, admitted between June 2022 and June 2024, were selected as study participants. Based on diagnosis records, 274 patients were assigned to the unipolar depression group, and 128 patients to the bipolar depression group. A total of 128 patients were matched between the two groups using the propensity score matching method. Demographic data, clinical characteristics, and biological indicators were compared between the two groups. The biological markers assessed included neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), serum triiodothyronine (T3), thyroxine (T4), free thyroid hormones (fT3, fT4), thyroid-stimulating hormone (TSH), complement 3 (C3), complement 4 (C4), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Binomial logistic regression analysis was employed to control for confounding factors and to explore the predictors of bipolar depression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of clinical features and biological markers for bipolar depression. Statistically significant differences were observed between the unipolar depression and bipolar depression groups with respect to life events (χ² = 15.397, P = 0.000), CRP (Z = 6.717, P = 0.000), TSH (Z = 1.988, P = 0.047), C3 (Z = 5.682, P = 0.000), C4 (Z = 4.216, P = 0.000), and IgM (Z = 2.304, P = 0.021). Logistic regression analysis indicated that life events (OR = 4.552, 95% CI = 2.238–9.257), CRP (OR = 13.886, 95% CI = 5.290-36.452), and IgM (OR = 0.561, 95% CI = 0.325–0.970) were associated with bipolar depression. ROC curve analysis revealed that the area under the curve (AUC) for the logistic regression model predicting bipolar depression was 0.806, with a sensitivity of 61.7% and a specificity of 85.9%. Compared to unipolar depression, bipolar depression was associated with the absence of life events, elevated CRP levels, and reduced IgM levels. The combined diagnostic model proved more effective in distinguishing bipolar depression from unipolar depression.

Background and Hypothesis: Schizo-obsessive comorbidity (SOC), defined as obsessive–compulsive symptoms (OCS) in schizophrenia (SCZ), is linked to severe psychopathology and poor prognosis. Schizophrenia and obsessive–compulsive disorder (OCD) share cognitive impairments, particularly in inhibition and cognitive flexibility, which may underlie SOC. However, little is known regarding the underlying neural mechanisms of SOC. We aimed to directly compare the inhibition- and cognitive flexibility-related neural activations between patients with SOC, SCZ, OCD, and healthy controls (HCs). Study Design: Twenty-eight patients with SOC, 33 SCZ patients, 30 OCD patients, and 33 HCs undertook fMRI while performing the combined shifting go/no-go task. We analyzed the shifting-related (shift vs go) and stopping-related (no-go vs go) activations among the different diagnostic groups. Study Results: Compared to HCs, the 3 clinical groups showed significant shifting-related hypoactivation in the left postcentral gyrus, left paracentral lobule, left supplementary motor area, and right superior frontal gyrus, with SOC exhibiting significantly lower activation than SCZ and OCD patients. Regarding stopping, OCD patients showed significant hyperactivation in the left precuneus compared with SCZ patients and HCs. Like OCD patients, SOC patients also exhibited greater hyperactivation than SCZ patients. Behaviorally, SOC and SCZ patients made significantly more commission errors than OCD patients, with SCZ also having more commission errors than HCs. Furthermore, SOC and SCZ made more shifting errors than HCs; and SOC made more shifting errors than SCZ and OCD patients. Conclusions: All 3 clinical groups shared cognitive inflexibility. Moreover, the presence of the 2 features appears to amplify the neural alterations, implicating “additive effects.”