Cognitive Enhancers in Schizophrenia: a Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms

Background: Schizophrenia is a severe and enduring disease and is one of the leading causes of disability worldwide. Cognitive impairment is a core clinical symptom that plays a crucial role in functional outcomes and prognosis, thus making it a relevant treatment target. The aim of this study was to assess the efficacy of alpha-7 nicotinic acetylcholine receptor agonists (alpha 7 nAChR) as adjunctive treatment to enhance cognition and ameliorate negative symptoms in patients with schizophrenia. Methods: A search strategy was developed for MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to May 2019. We included randomized controlled trials (RCTs) that compared antipsychotic treatment plus alpha 7 nAChR agonists with antipsychotic treatment plus placebo and determined their effects on the main cognitive domains proposed by the MATRICS initiative and on negative symptoms. Two authors independently reviewed study eligibility and data extraction and assessed the risk of bias of the studies included. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, we used a random-effects model and assessed the quality of the evidence. Results: Thirteen studies were included in the quantitative analysis. No differences were found in any of the cognitive domains assessed in four RCTs (n = 414). In contrast, nine RCTs (n = 978) presented a small effect in support of alpha 7 nAChR agonists for negative symptoms [standardized mean difference -0.28, 95% CI (-0.56 to -0.00); P = 0.05], even though the confidence to support this evidence is low according to the GRADE system. Conclusions: Current evidence is too weak to consider alpha 7 nAChR agonists as an effective add-on treatment to antipsychotics to enhance cognition and negative symptoms.The work conducted at the University of the Basque Country was funded by public grants GIU14/27, PPGA18/03, and IT1232-1

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females

BackgroundDeficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset.Materials and methodsThe initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up.ResultsFEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning.ConclusionOur data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended