Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Background: Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear. Objective: To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators. Methods: We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression. Results: Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency. Conclusions: Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

Associations of C-Reactive Protein, Free Triiodothyronine, Thyroid Stimulating Hormone and Creatinine Levels with Agitation in Patients with Schizophrenia: A Comparative Cross-Sectional Study.

PURPOSE: Agitation is prevalent among inpatients with schizophrenia. The aim of this study was to investigate whether biochemical parameters are associated with agitation in schizophrenia. PATIENTS AND METHODS: Agitation was evaluated by the Positive and Negative Syndrome Scale-Excited Component questionnaire (PANSS-EC). Fasting serum levels of C-reactive protein (CRP), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), uric acid (UA), creatinine, glucose and lipids were measured. RESULTS: The analysis included 154 inpatients with schizophrenia (71 with agitation, 83 without agitation) and 75 healthy control subjects. Patients with schizophrenia and agitation had higher serum levels of CRP, FT3, FT4 and UA as well as lower levels of serum TSH and creatinine than patients without agitation (all P < 0.05). Multivariate logistic regression analysis indicated that serum CRP (odds ratio [OR] = 1.470, P = 0.001), FT3 (OR = 13.026, P < 0.001), TSH (OR = 0.758, P = 0.033) and creatinine (OR = 0.965, P = 0.004) were significantly associated with agitation in schizophrenia. CRP, FT3, TSH and creatinine achieved an area under the ROC curve of 0.626, 0.728, 0.620 and 0.663 respectively in discriminating schizophrenia with or without agitation. CONCLUSION: Increased serum CRP and FT3 levels and decreased serum TSH and creatinine levels are independent risk factors for agitation in hospitalized patients with schizophrenia. Inflammation, thyroid hormones and renal function may be involved in the pathogenesis of agitation in schizophrenia.

The risk of male adult alcohol dependence: The role of the adverse childhood experiences and ecological executive function.

OBJECTIVE: To explore the association between male adult alcohol dependence and their adverse childhood experiences as well as ecological executive function. METHODS: The questionnaires of Adverse Childhood Experiences (ACEs) and Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) were adopted for the assessments of 102 alcohol dependent patients who were diagnosed according to the criteria defined by the International Classification of diseases and related health problems (ICD-10) and 106 healthy volunteers, and the differences between patients and healthy volunteers were analyzed. RESULTS: The percentage of adverse childhood experiences in alcohol dependent patients was significantly higher than that in healthy volunteers (χ(2)=17.28, P<0.01); and the incidences of emotional abuse, physical neglect, violence witness, and substance abuse were significantly higher in alcohol dependent patients than those in healthy volunteers (χ(2)=4.59, 4.46, 10.51, and 44.09 respectively; P<0.05). The ecological executive function analysis showed that the BRIEF total score and scores for each item were all significantly higher in alcohol dependent patients than those of healthy volunteers (P<0.01). CONCLUSIONS: The adult alcohol dependence was associated with their adverse childhood experiences and ecological executive function. Then physical neglect and substance abuse of parents in childhood, and emotional control defect in the ecological executive function showed strong association with adult alcohol dependence.

HIV transactivator of transcription enhances methamphetamine-induced Parkinson's-like behavior in the rats.

Abuse of methamphetamine (MA) increases the risk of infection of HIV-1, induces considerable neurotoxicity in several brain regions, and impairs the motor and cognitive function in individuals. HIV-1 transactivator of transcription (Tat) has also shown the potent capability to induce neuronal death and impaired brain function. The present study aims to study the synergistic effect of MA and Tat on cytokine synthesis in substantia nigra, striatal dopamine content, and behavioral performance in the rats. Although increased expression of cytokines (interleukin-1ß and tumor necrosis factor-α) was observed in the substantia nigra in the rats receiving either MA or Tat alone, a combination of MA and Tat induced a larger and more sustained upregulation of cytokines. In the rats receiving either MA or Tat alone, significant loss in striatal dopamine content was found, which was further exacerbated in the rats receiving both MA and Tat. In the rats receiving either MA or Tat alone, significantly lower performance in the rotarod test and open-field test was observed, whereas the rats receiving both MA and Tat showed more sustained behavioral impairments. These results suggested that Tat protein synergized with MA to induce central neuroinflammation and impair the dopaminergic transmission, thus leading to sustained Parkinson's-like behavior.