M176. INTESTINAL PERMEABILITY AND LOW-GRADE CHRONIC INFLAMMATION IN SCHIZOPHRENIA: DO THEY INFLUENCE COGNITION AND COGNITIVE RESERVE?

BACKGROUND: Higher intestinal-permeability is known to cause low-grade chronic inflammation, which seems to participate in the development and worsening of psychotic disorders both in first-episode psychosis (FEP) and schizophrenia (SCZ) patients. Moreover, in psychotic disorders, inflammation has been linked to cognition and cognitive reserve (CR). The aim of this study is to assess the relation between intestinal-permeability, low-grade chronic inflammation, cognition and cognitive reserve in psychotic disorders. METHODS: Observational, cross-sectional and multisite study including four centers in Spain (Grant from Fondo de Investigación Sanitaria, PI17/00246). A total of 500 adult patients with DSM-5 SCZ-spectrum disorder at any stage of the disease were recruited. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Disease severity was assessed using the Clinical Global Impression (CGI) scale and functioning was assessed using the Global Assessment of Functioning (GAF) scale. The intestinal-permeability was estimated with the “Permeable-Intestine-syndrome questionnaire”. The diet was assessed with the “Mediterranean-diet-adherence questionnaire”. Exercise was measured with the “International Physical Activity Questionnaire (IPAQ)”. Cognition was measured with the SCIP-S scale. CR was assessed with the Cognitive Reserve Assessment Scale in Health (CRASH), which is a scale developed to measure CR specifically for patients with severe mental illness. Correlations between CRASH scores and the remainder variables were performed. RESULTS: For the present study we included only the subjects who had CRASH score, a total of 112 patients, 42.7% female, aged 40.61±12.4 (mean±SD). Substance use was present in 44.3%. The CRASH score was 33.30±15.72 (mean±SD) and was associated with negative (but not positive) psychotic symptoms assessed by PANSS (PANSS negative; rp=-3.98; p=0.001, PANSS general; rp=-2.13; p=0.038, GAF; rp=0.410; p<0.0001, CGI; rp=-0.30; p=0.002, IPAQ; rs=0.224; p=0.025 and the permeability-scale; rs=-0.266; p=0.008. All cognitive domains (assessed by SCIP-S) were associated to CRASH: verbal learning immediate (rp=0.584; p<0.0001) and differed (rp=0.515; p<0.0001), working memory (rp=0.539; p<0.0001), verbal fluency (rs=0.485; p<0.0001) and processing speed (rp=0.584; p<0.0001). No significant associations were found with Mediterranean-diet scale (rs=0.195; p=0.056), IMC (rs=-0.192; p=0.063), C-reactive protein (rs=-0.104; p=0.278) and the IPAQ-resting scale and permeability-scale (rs=0.119; p=0.244). DISCUSSION: 1. High CR in SCZ-spectrum disorders is associated with low intestinal permeability, probably mediated by low-grade chronic inflammation through exercise and diet, although the latter was not significantly associated in this analysis. 2. A higher CR in SCZ-spectrum disorders may contribute to less negative psychotic symptoms, better functioning, a lower severity of illness, and better cognitive outcomes. 3. The complex inflammation-intestinal-permeability may play a role in the pathophysiology of SCZ-spectrum disorders, mediated by daily-life factors (exercise and diet). 4. Focused interventions on the modification of daily-life factors could reduce the influence of the complex inflammation-intestinal-permeability and secondarily reduce symptoms, and improve cognition, CR and functioning in SCZ-spectrum disorders. 5. Specific programs addressed to improve CR and functioning conducted at the early stages of the psychotic illness may be helpful in order to prevent cognitive and functional decline.