Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging

摘要

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups ( P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 ( P = .005) and interleukin-10 ( P = .002) compared with controls as well as increased levels of interleukin-6 ( p = 0.014) and CCL24 ( P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls ( P = .015), and a similar tendency was found in patients compared with controls ( P = .045). Glutathione peroxidase activity was decreased in patients compared with controls ( P = .006) and siblings ( P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted. bipolar disorder , siblings , biomarkers , telomere , aging. Significance Statement Bipolar disorder (BD) presents with progressive clinical and neurobiological changes probably associated with poor metabolic stress compensation. Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for BD. Aging and senescence processes could contribute to the search for new and promising molecular targets to help explain and ameliorate neuroprogression in BD. This study reinforces that aging is probably associated with the neuropathological processes seen in BD and shows that unaffected siblings may present senescence features. Prospective studies of the neurobiology and clinical features of those with a high familiar risk for BD may help researchers identifying heritable subphenotypes of the disorder and assess how this familial risk is clinically expressed. Furthermore, research with siblings of patients with BD may shed light on the pathophysiology of the condition.