ABSTRACT
INTRODUCTION: First-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. METHODS: Seventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60-70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. RESULTS: Participants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (-3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (-22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (-13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DISCUSSION: Regular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.
ABSTRACT
Much of the early research into AD relies on a neuron-centric view of the brain, however, evidence of multiple altered cellular interactions between glial cells and the vasculature early in AD has been demonstrated. As such, alterations in astrocyte function are widely recognized a contributing factor in the pathogenesis of AD. The processes by which astrocytes may be involved in AD make them an interesting target for therapeutic intervention, but in order for this to be most effective, there is a need for the specific mechanisms involving astrocyte dysfunction to be investigated. "α disintegrin and metalloproteinase" 10 (ADAM10) is capable of proteolytic cleavage of the amyloid precursor protein which prevents amyloid-ß generation. As such ADAM10 has been identified as an interesting enzyme in AD pathology. ADAM10 is also known to play a role in a significant number of cellular processes, most notable in notch signaling and in inflammatory processes. There is a growing research base for the involvement of ADAM10 in regulating astrocytic function, primarily from an immune perspective. This review aims to bring together available evidence for ADAM10 activity in astrocytes, and how this relates to AD pathology.
ABSTRACT
OBJECTIVE: To provide a comprehensive analysis of cytokine perturbations in antipsychotic-naïve first-episode psychosis (FEP) populations and assess the relationship between inflammatory biomarkers and negative symptom severity. METHODS: A systematic review and meta-analysis following PRISMA guidelines were conducted. A total of 1042 records were identified via systematic search of EMBASE, MEDLINE and APA PsycInfo databases. Sixteen studies met the inclusion criteria and were eligible for inclusion in the review. Ten of these studies had sufficient data for inclusion in a random effects, pooled-effect meta-analysis. RESULTS: A significant and large effect size was reported for IFN-γ, IL-6 and IL-12, and a moderate effect size reported for IL-17 (p = <0.05) in people with antipsychotic naive first episode psychosis, compared to healthy controls, suggesting a significant elevation in proinflammatory cytokine concentration. Non-significant effect sizes were reported for TNF-α, IL-1ß, IL-2, IL-4, IL-8 and IL-10 (p = >0.05). Regarding proinflammatory cytokines and relationships to negative symptomology, moderate positive relationships were reported for negative symptoms and IL-1ß, IL-2, IL-6 and TNF-α, across four studies. For anti-inflammatory cytokines, one strong and one weak-to-moderate negative relationship was described for IL-10 and negative symptoms. Contrastingly, a strong positive relationship was reported for IL-4 and negative symptoms. CONCLUSION: There is evidence of significantly elevated proinflammatory cytokines in antipsychotic-naïve FEP populations, alongside promising findings from cohort data suggesting an interaction between inflammation and primary negative symptomology. Future studies should seek to come to a consensus on a panel of cytokines that relate most specifically to negative symptoms, and consider longitudinal studies to investigate how cytokine fluctuations may relate to exacerbation of symptoms.
