May Non-antipsychotic Drugs Improve Cognition of Schizophrenia Patients?

Buoli, Massimiliano; Altamura, A.C.

doi:10.1055/s-0034-1396801

Cited by 16 publications

(9 citation statements)

References 98 publications

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“…Visual learning/memory, attention and executive function were the cognitive domains with significant changes in minocycline or pregnenolone augmentation trials. Although these results are promising in that attention, memory and executive function are the most damaged cognitive domains in schizophrenia (Buoli and Altamura, 2015), some caution seems justified as the cognitive scales used in each trial are quite heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials

Cho

Lee

Kwak

et al. 2019

Aust N Z J Psychiatry

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Objective: Recent evidence suggests that adjuvant anti-inflammatory agents could improve the symptoms of patients with schizophrenia. However, the effects of the adjuvant anti-inflammatory agents on cognitive function, general functioning and side effects have not yet been systematically investigated. The present meta-analysis aimed to explore the effects of anti-inflammatory agents in patients with schizophrenia comprehensively. Method: We performed a literature search in online databases, including PubMed, EMBASE and the Cochrane Database of Systematic Reviews. Randomized, placebo-controlled double-blind studies that investigated clinical outcomes including psychopathology, neurocognition, general functioning and extrapyramidal side effects were included. The examined anti-inflammatory agents included aspirin, celecoxib, omega-3 fatty acids, estrogen, selective estrogen receptor modulator, pregnenolone, N-acetylcysteine, minocycline, davunetide and erythropoietin. Results: Sixty-two double-blind randomized clinical trials studying 2914 patients with schizophrenia met the inclusion criteria for quantitative analysis. Significant overall effects were found for anti-inflammatory agents for reducing total, positive and negative symptom scores in the Positive and Negative Syndrome Scale. Cognitive improvements were significant with minocycline and pregnenolone augmentation therapy. General functioning was significantly enhanced by overall anti-inflammatory agents. There were no significant differences in side effects compared with placebo. Baseline total Positive and Negative Syndrome Scale score and illness duration were identified as moderating factors in the effects of anti-inflammatory augmentation on psychiatric symptom improvements. Conclusion: The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone. However, future studies could focus on patients with homogeneous clinical profile to figure out more detailed effects of anti-inflammatory therapy.

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Section: Discussionmentioning

confidence: 99%

Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials

Cho

Lee

Kwak

et al. 2019

Aust N Z J Psychiatry

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“…Interventions on the inflammatory and/or oxidative level seem to have a neuroprotective role (Keller et al, 2013), comparable to the neuroprotective effect of cognitive therapy (Eack et al, 2010; Thorsen et al, 2014) or physical exercise (Vakhrusheva et al, 2016). However, antioxidant and antiinflammatory strategies for the treatment of psychosis still give conflicting results, with little evidence for their efficacy in the management of some psychopathological dimensions such as cognition (Buoli and Altamura, 2015). The use of average values of inflammatory and oxidative markers for heterogeneous populations instead of using biomarkers to stratify patients may be one reason.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Inflammation in Early Onset First Episode Psychosis: A Systematic Review and Meta-Analysis

Fraguas

Díaz‐Caneja

Rodríguez-Quiroga

et al. 2017

International Journal of Neuropsychopharmacology

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Background:People with schizophrenia and other psychosis show increased proinflammatory and prooxidative status. However, the few studies that have specifically assessed oxidative and inflammatory markers in early onset psychosis (onset before age 18) have shown contradictory results.Methods:Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for systematic reviews and meta-analyses were used to conduct a systematic literature search to detect studies comparing inflammatory and oxidative markers in early onset psychosis patients and healthy controls.Results:Seven studies met criteria for the qualitative analysis. Four studies met criteria for meta-analysis, comprising an overall sample of 261 early onset psychosis patients and 246 healthy controls. Six independent meta-analyses were performed for catalase, glutathione, glutathione peroxidase, superoxide dismutase, total antioxidant status, and cell/DNA oxidative damage. No significant differences were found between early onset psychosis patients and controls in any of the parameters assessed. Heterogeneity among studies was high. Qualitative analysis of individual studies showed an association of inflammatory and oxidative markers with clinical, cognitive, and neurobiological outcomes, especially in longitudinal assessments.Conclusions:Despite the lack of significant differences between early onset psychosis patients and controls in the oxidative markers assessed in the meta-analyses, results based on individual studies suggest that greater inflammation and oxidative stress might lead to poorer outcomes in patients with first episodes of early onset psychosis.

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“…Yet these impairments are mostly resistant to available treatments (Buoli and Altamura, 2015; Lett et al, 2014; Millan et al, 2012); greater understanding of their underlying neurobiology could facilitate the development of novel therapies (Arguello and Gogos, 2010). To this end, we have studied the neural basis of cognitive deficits in Df(16)A +/− mice, which model a microdeletion on chromosome 22q11.2 that accounts for up to 1%–2% of sporadic schizophrenia cases (Karayiorgou et al, 1995; Xu et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Developmental Inhibition of Gsk3 Rescues Behavioral and Neurophysiological Deficits in a Mouse Model of Schizophrenia Predisposition

Tamura

Mukai

Gordon

et al. 2016

Neuron

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SUMMARY While the genetic basis of schizophrenia is increasingly well-characterized, novel treatments will require establishing mechanistic relationships between specific risk genes and core phenotypes. Rare, highly-penetrant risk genes such as the 22q11.2 microdeletion are promising in this regard. Df(16)A+/− mice, which carry a homologous microdeletion, have deficits in hippocampal-prefrontal connectivity that correlate with deficits in spatial working memory. These mice also have deficits in axonal development that are accompanied by dysregulated Gsk3β signaling and can be rescued by Gsk3 antagonists. Here, we show that developmental inhibition of Gsk3 rescues deficits in hippocampal-prefrontal connectivity, task-related neural activity, and spatial working memory behavior in Df(16)A+/− mice. Taken together, these results provide mechanistic insight into how the microdeletion results in cognitive deficits, and suggest possible targets for novel therapies.

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May Non-antipsychotic Drugs Improve Cognition of Schizophrenia Patients?

Cited by 16 publications

References 98 publications

Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials

Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials

Oxidative Stress and Inflammation in Early Onset First Episode Psychosis: A Systematic Review and Meta-Analysis

Developmental Inhibition of Gsk3 Rescues Behavioral and Neurophysiological Deficits in a Mouse Model of Schizophrenia Predisposition

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