Exercise as a promoter of neurocognitive improvement in people with psychiatric disorders and comorbid obesity: A randomized controlled trial

•The psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation.•Exercise is crucial to improve and maintain healthy lifestyles.•Aerobic exercise could be an effective promoter of neurocognitive improvement across psychiatric disorders with comorbid obesity.•Physical activity programs may have positive impact on neurocognitive and functional performance in individuals with psychiatric disorders and comorbid obesity.•Exercise influences inflammatory, oxidative, vascular, and cardio-metabolic pathways, and modulate cognition. The psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation. Exercise is crucial to improve and maintain healthy lifestyles. This randomized controlled trial tested the efficacy of aerobic exercise as promoter of neurocognitive improvement across psychiatric disorders with comorbid obesity (OB). Patients with major depressive disorder, bipolar disorder and, schizophrenia and with comorbid OB (n = 29) received brief healthy lifestyle counseling and were randomized into two groups: guided physical activity group (GPAG) (n = 10) which included 12 weeks of guided-exercise of moderate intensity and frequency, and incentive of autonomous physical activity proposals by the specialist. Standard physical activity group (SPAG) (n = 19) continue with their usual daily physical activity, without guidance or incentives, over 12 weeks. Peripheral blood biomarkers of inflammation, oxidative stress, vascular mechanisms, and metabolic activity, as well as neurocognitive and functional performance were assessed twice, before and after intervention. Mixed one-way analysis of variance and linear regression analyses were performed. Individuals in GPAG showed better neurocognitive and functional performance than individuals in SPAG after physical activity training (p < 0.05; η²p = 0.14 to 0.15). A significant improvement in cognition before and after the physical activity training in the GPAG group was found (p < 0.0001; η²p = 0.29). In all cases, the effect size was from moderate to large. Inflammatory activity (interleukin [IL-6]), oxidative (mitochondrial reactive oxygen species [mROS] and mitochondrial membrane potential [ΔΨm]) and inter cellular adhesion molecule 1 [ICAM1], leukocyte-endothelium adhesion [LEPMN], and p-selectin [PSEL]) levels, and cardio-metabolic (low-density lipoprotein [LDL], systolic blood pressure [SBP], and insulin) processes were significan