25.2 TELOMERE LENGTH AND PRO-INFLAMMATORY CHEMOKINE AS PATHOLOGICAL AGING BIOMARKERS IN SCHIZOPHRENIA: RELATIONSHIP WITH EPISODIC MEMORY PERFORMANCE AND TOTAL GRAY VOLUME

Abstract

Background: Schizophrenia (SZ) is associated with increased somatic morbidity typically related to processes of aging, such as cardiovascular disease and metabolic abnormalities. Furthermore, individuals with SZ have increased mortality and reduced life span. These observations of increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, may indicate that subjects with SZ have a pathological accelerated aging However, although there is evidence supporting this hypothesis, the neurobiological underpinnings are still unclear. Therefore, this presentation aims to suggest possible mechanisms to this hypothesis. A suggested biomarker of aging is the length of telomeres (TL), which are DNA-protein structures that protect the ends of chromosomes and progressively shorten with each cell division. Inflammatory processes, such as dysregulation in cytokines, may influence TL. The pro-inflammatory chemokine CCL11, a type of cytokine, was described as an age-related systemic factor associated with decreased neurogenesis in hippocampus and impaired memory in mice, that was increased in chronic but not in recent onset individuals with SZ. Thus, these biomarkers could be associated with brain volume loss and memory impairments, which might be behavioral and structural outcomes of aging. Methods: We included 48 individuals with SZ and 64 healthy subjects (HC). Participants had the same socioeconomic and educational background. They underwent clinical and memory assessments, structural T1 MRI 1.5T, and had their peripheral blood drawn for biochemical analysis. Comparisons of group means and correlations were performed. We aimed to evaluate the relationships of TL and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume, and episodic memory performance in individuals with SZ compared to HC. Results: Our results showed that SZ had shorter TL and increased CCL11 compared to HC. Additionally, individuals with SZ had reduced GM volume and worse episodic memory performance than HC. In SZ, shorter TL was related to increased CCL11, and both biomarkers were related to reduced GM volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. TL mediated the effects of duration of illness to memory performance. In HC, there were no significant correlations except for the expected relationship between memory and GM. Conclusions: We saw associations between increased CCL11, shorter TL, reduced GM volume, and decreased episodic memory in SZ, which were all related to longer duration of illness. These results suggest that it is not age itself, but the impact of the disease associated with a pathological aging that might lead to a worse outcome. Chronic pro-inflammatory processes could influence the body's capacity to absorb damage over time. This could have impacts on the brain that might lead to structural and functional consequences, such as loss of GM, which in turn could elicit behavioral impairments, such as memory deficits. Although preliminary, our data point to potentially important mechanisms related to neural and cognitive impairment associated with psychosis consistent with the hypothesis of accelerated aging in SZ.