Acta Psychiatrica Scandinavica最新文献

Introduction: Major depressive disorder (MDD) and bipolar disorder (BD) are often associated with persistent cognitive deficits that impair psychosocial functioning. While pro-cognitive interventions show promise, trial findings are inconsistent, potentially due to baseline factors influencing treatment response. This systematic review summarizes evidence on pre-treatment characteristics associated with cognitive improvement and offers methodological recommendations.

Methods: A systematic search was conducted in PubMed/MEDLINE, EMBASE, PsycINFO, and Cochrane Library from inception to February 28, 2025. Eligible studies included primary or secondary analyses of randomized controlled trials (RCTs) investigating predictors of cognitive response to pro-cognitive interventions in MDD and/or BD. Two researchers independently conducted study selection and risk of bias assessments. Findings were synthesized qualitatively.

Results: Forty studies (N = 3864) were identified, covering pharmacological treatments (k = 20; N = 2299), psychological therapies (k = 16; N = 1165), brain stimulation (k = 2; N = 168), and physical activity (k = 2; N = 232). Poorer baseline cognitive performance was the most consistent predictor of greater cognitive improvement, though the direction of the effect was not entirely uniform across all studies. Baseline depression severity showed no significant association with cognitive outcomes. Age, education, sex, IQ, diagnosis, and medication status were similarly non-predictive. Risk of bias was high in 77% of studies, mainly due to deviations from specified outcomes, poor randomization processes, and inconsistent handling of missing data. Considerable heterogeneity in interventions, outcome measures, and sample characteristics limited replicability and precluded meta-analysis.

Conclusion: Poorer baseline cognition emerged as the most reliable predictor of greater cognitive improvement across interventions. More rigorous, well-powered studies are needed to replicate these findings and identify robust predictors to guide personalized pro-cognitive treatment approaches in mood disorders.

Background: Cognitive deficits are common in individuals with bipolar disorder (BD), but there is considerable variability in cognitive functioning. Childhood maltreatment (CM), which is frequently reported in BD, has been linked to poorer cognitive performance, potentially through mechanisms such as inflammation. However, the relationship between CM and global cognition and the mediating role of inflammation in BD warrant further investigation.

Methods: The study sample consisted of 112 BD individuals and 83 healthy controls (HCs). Participants completed the MATRICS Consensus Cognitive Battery (MCCB), the Wisconsin Card Sorting Test, and the Childhood Trauma Questionnaire (CTQ). A composite inflammation index was created using blood levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α, and was used in primary analyses.

Results: The BD group, compared to HC, showed higher levels of inflammation and CM. Across the entire sample, higher total CM was associated with poorer global cognitive performance, with a medium effect size, even after accounting for diagnostic status. The associations were evident across all CM subscales. Specific cognitive domains affected included speed of processing, working memory, visual learning, and reasoning and problem solving. The association between CM and poorer global cognitive performance was partially mediated by inflammation (indirect effect: β = -0.048, CI = -0.10, -0.009). Within the BD group, higher total CM was similarly associated with worse global cognitive performance. The associations were evident across all CM subscales, except for physical neglect. Significant associations were observed between total CM and MCCB domains of speed of processing, attention and vigilance, working memory, visual learning, reasoning and problem solving, as well as cognitive flexibility. Within the HC group, only emotional neglect and physical neglect were associated with poorer global cognition.

Conclusions: This study provides evidence that total CM and its subscales are associated with poorer global cognitive performance in a sample of individuals with BD and HC, with stronger associations found within the BD group. In addition, inflammation partially mediated the relationship between CM and global cognition. These findings highlight the importance of trauma-informed and cognition-focused interventions aimed at enhancing cognitive outcomes and slowing cognitive decline in individuals with BD who have a history of CM. Furthermore, the results suggest that while inflammation plays a role in the CM-cognition link, its effects are complex and likely interact with other biological and environmental factors.

Background: Schizophrenia is characterized by positive, negative, and cognitive symptoms. Current pharmacological treatments often fail to address cognitive deficits. In this review of clinical trials, we aim to identify studies that explore neurobiological (non-psychological) strategies to address Cognitive Impairment Associated with Schizophrenia (CIAS).

Methods: A search of clinical trial databases was conducted through US National Institutes of Health's ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) on August 2, 2024, with complementary searches performed on July 4 and 10, 2025, for each respective database to update the results.

Results: We identified 510 relevant interventional studies that objectively measured cognitive performance. Most trials were conducted in the United States (36.4%) and focused on treatment (79%), with randomized designs (88%), investigating drugs (56%), devices (33%), and dietary supplements (10%). Of these trials, 17% reported positive pro-cognitive evidence. Glutamate modulators were the most studied drug category (63 trials), with positive results for sarcosine, BI425809 (Iclepertin), d-serine, d-cycloserine, and minocycline in small-scale trials, although the results were not replicated in larger studies. Nicotinic receptor modulators like ABT-126 and encenicline also showed some cognitive benefits. Device-based interventions, particularly rTMS and iTBS, demonstrated improvements in global cognition, working memory, attention, and processing speed in a subset of trials.

Conclusion: In this comprehensive overview of clinical trials on pro-cognitive agents in schizophrenia, we identify emerging opportunities but also acknowledge a lack of replicated evidence. Despite extensive attempts to address CIAS, it remains an undertreated domain, and future trials should explore better ways to treat this important condition.

Introduction: Bipolar disorder (BD) and schizophrenia (SZ) are serious mental illnesses (SMI) with overlapping symptoms but distinct differences in onset and course. Sex differences are an area of growing interest in SMI. This study aims to examine potential interactions between sex and diagnosis across a broad range of variables, to compare males and females within SZ and BD, and to investigate sex-specific group differences.

Methods: A total of 1516 individuals were included in a cross-sectional study using baseline data from the multicenter PsyCourse Study, including BD (n = 543), SZ (n = 517), and healthy controls (HC) (n = 456). Sociodemographic characteristics, clinical symptoms, psychosocial functioning, quality of life, neurocognitive performance, and somatic comorbidities were assessed. Generalized linear models were used to analyze differences between groups and sexes. False Discovery Rate (FDR) and Bonferroni post hoc comparisons were performed.

Results: Significant interactions were identified in age (p = 0.001), age at treatment (p = 0.05), illness duration (p = 0.03), illicit drug use (p = 0.01), and smoking (p = 0.05). Differences in substance use were observed across groups and sexes, with the highest rates found in males with SZ. The BD group showed better functioning and neurocognitive performance compared with the SZ group. Within the BD group, females reported better performance in verbal memory (p = 0.003) and psychomotor speed (p < 0.001) than males. Moreover, both females and males with SMI showed higher rates of thyroid alterations compared with HC (p = 0.01 for females and p = 0.002 for males).

Conclusions: Significant sex differences were observed in substance use and somatic comorbidities. Interactions between diagnosis and sex underscore the importance of considering both factors in clinical assessments. These findings highlight the need to tailor sex-specific treatment for each patient. Further research is needed to explore the role of sex hormones and other biological and societal factors in the presentation and course of these disorders.