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

Abstract

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.

BDNF Integrity in Ageing and Stress

“…For example, in a sample of bipolar patients and their siblings, telomere length was different between the three groups studied, patients, siblings and healthy volunteer controls with both patients and siblings showing a shorter telomeric length, T/S ratio, compared with the healthy controls. 40 Further, patients showed also increased levels of interleukin-6 and interleukin-10, pro-inflammatory cytokines, compared with the controls as well as increased levels of interleukin-6 and CCL24, myeloid progenitor inhibitory factor 2 encoded by the CCL24 gene, compared with their siblings. The C-C motif chemokine 11 levels were increased in siblings compared with the controls with similar tendencies found in the patients compared with the controls.…”

Biomarkers in first-degree relatives of patients with bipolar disorder: what can they tell us?

“…This finding was recently replicated in another population of high-risk siblings. 4 The concept and investigation of endophenotypes has emerged as a strategy to overcome methodological difficulties inherent to the classical investigation of complex heterogeneous disorders, such as BD. The traditional definition of endophenotypes states that: i) they should be associated with the illness in the population; ii) they should be heritable and state-independent (i.e., detectable regardless of whether the illness is active); iii) they should co-segregate within families; and iv) they should be detectable in unaffected relatives of patients at a higher rate than in the general population.…”

“…The recent development of alpha-7 nicotinic receptor agonists as cognitive enhancers in schizophrenia, as well as in Alzheimer's disease, may also require the careful regulation of melatonin synthesis, given that melatonin regulates the levels and activity of this nicotinic receptor, again as shown by Markus et al 4 The alpha-7 nicotinic receptor is also a significant inhibitor of glial and immune cell reactivity, suggesting that its interaction with levels of melatonin is likely to modulate its clinical utility.…”

Investigação do comprimento telomérico em famílias com vários afetados pelo transtorno bipolar

“…O que se têm visto mais recentemente são evidências apoiando a existência de anormalidades clínicas e neurobiológicas progressivas em indivíduos com TB, provavelmente associadas a um envelhecimento celular acelerado nesses pacientes (Vasconcelos-Moreno et al, 2017). Observou-se que há uma grande quantidade de integração e sobreposição entre os mecanismos neurobiológicosincluindo alterações progressivas em nível molecular e celular, e na estrutura e função do sistema nervoso centralpresentes tanto no TB como nas doenças associadas ao envelhecimento (Rizzo et al, 2014;Lindqvist et al, 2015;Jacoby et al, 2016;Vasconcelos-Moreno et al, 2017).…”

“…As doenças clínicas que são mais frequentes no TB são aquelas mais comumente vistas em pessoas de idades avançadas, relacionadas com o envelhecimento, como, por exemplo, doenças cardiovasculares, osteoporose, câncer e demência que têm instigado alguns pesquisadores a caracterizarem o TB como um distúrbio do envelhecimento acelerado (Simon et al, 2006;Rizzo et al, 2014). Sugere-se, assim, que um envelhecimento patológico pode ser componente da doença, evidenciado pelas alterações neurobiológicas e neuroprogressivas similares tanto no TB como no envelhecimento, como: alterações a nível cerebral (diminuição do volume cerebral), bem como alterações a nível imunológico (aumento de citocinas inflamatórias e de células T CD8 + CD28 − circulantes, do inglês cluster of differentiation); alterações mitocondriais; estresse oxidativo (aumento de óxido nítrico, por exemplo) e também senescência celular (encurtamento dos telômeros) (Jacoby et al, 2016;Vasconcelos-Moreno et al, 2017).…”