Background: Depression is a common disorder in older adults (patients aged more than 65 years) that is associated with emotional suffering, increased disability, functional impairment/activity limitations and costs and negative health outcomes over time. Current research in the neuropsychiatric field is focusing no longer on a single substrate or neurotransmitter system (such as altered serotonin or catecholamine neurotransmission) but rather on integrating multiple parameters (as pro-inflammatory agents and oxidative stress), as a reflection of the physio-pathological complexity of mental disorders, seen as real neuroendocrine and systemic dysfunctions. Aim: to evaluate the clinical status in "over-65" patients affected by depression and anxiety through psychiatric scales; to measure in these patients and control subjects, matched by gender and age, 5 parameters of oxidative stress in plasma: the Advanced products of protein oxidation (AOPP), the Ferric reducing antioxidant power (FRAP), total thiols (-R-SH), Superoxide dismutase (SOD), or anion superoxide conversion to H2O2, Catalase (CAT), or H2O2 conversion to H2O and O2; to appraise the plasma levels of 3 pro-inflammatory cytokines secreted by innate immunity, IL-6, IL-8 and TNFa in recuited patients as possible correlates of clinical symptoms and the oxidative stress biomarkers under investigation; to apply inferential statistic to assess between-groups differences as well as to preliminarily correlate the different variables under investigation. Methods: A total of 60 subjects aged ≥ 65 years were enrolled. Elderly subjects suffering from depression were recruited during their hospitalization in a psychiatric ward (n=30). The control subjects (n=30), were matched by age and sex, among non-depressed patients, without psychiatric pathologies and in treatment for minor pathologies affecting the peripheral nervous system. All patients were evaluated with HAM-D; GDS; HAM-A; MMSE; YMRS; RFL; SSI; ADL; IADL. Each patient underwent a fasting blood sample. Blood sample (10 ml) was collected in two tubes: a K-EDTA tube for all dosage and a lithium-heparin tube for the parameter FRAP. AOPP: spectrophotometric assay; evaluation of oxidative damage to proteins; the assay follows the protocol by Witko-Sarsat et al. (1996); the change in absorbance is measured at λ = 340 nm. Total thiols: spectrophotometric assay; rating reducing power -SH groups; The assay follows the protocol indicated by Hu in 1994. FRAP:spectrophotometric assay; rating plasma antioxidant power; the assay follows the protocol by Benzie and Strain (1996). SOD:competitive colorimetric assay kit; rating enzyme activity. CAT:colorimetric assay kit; rating enzyme activity. The pro-inflammatory cytokines, IL-6, IL-8 and TNF-a, were measured in plasma samples of patients by means of a same type of Immuno-enzyme ELISA assay kit. Results: About half of the sample presented comorbidity with an anxiety disorder. The sample was composed by patients already under treatment with antidepressants, presenting two or three somatic heath concerns and comorbidities. For what concerns the HAM-D items and the corresponding clinical presentation, elderly depressed patients of our sample presented high scores in depressed mood - expressed in a non-verbal way -suicide, work and interests, psychic and somatic anxiety, gastrointestinal symptoms and somatic symptoms in general, hypochondria. First of all, we observed a strong increase (more than +50%, on average) of an index of oxidative stress, AOPP in depressed vs. non-depressed patients. Concurrently, we also reported a strong reduction of antioxidant compounds in plasma, in terms of levels of Total thiols and FRAP antioxidant power. Levels of IL6, IL8 and TNFa measured in patients fitted within values reported in other study. We observed that both TNFa, and SOD activity, were positively correlated with AOPP protein chlorination. Indeed, we also reported that Total thiols, were negatively correlated with SOD level. Interestingly, we could report a negative correlation between IL8 and AOPP. We found that subjects with familiarity for depression had lower levels of IL8 than those without familiarity. No significant correlation between biochemical parameters and HAM-D, GDS, HAM-A rating scale scores was found. A negative correlation found between Total thiol and IADL score in severe depressed aged subjects was found. Patients showing higher items for the SSI scale of suicidal ideation had respectively lower IL8 levels and higher SOD activity. CAT activity and H2O2 scavenging was instead inversely correlated with cognitive abilities, appraised by the MINI mental state interview. Finally, a higher antioxidant power in plasma, FRAP, was found in subjects with a higher scholar education. Conclusion: this study show preliminary data; with the expansion of the sample size it will be possible to obtain statistically more consistent results. We found relevant change of ROS scavenging system in severe geriatric depression. These results are in any case a starting point towards a deeper investigation on specific components of the inflammatory and immune response possibly altered in different forms of depression.
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