Lipid peroxidation biomarkers in adolescents with or at high-risk for bipolar disorder

Abstract

Background Prior work suggests that adult bipolar disorder (BD) is associated with increased oxidative stress and inflammation. This exploratory study examined markers of lipid and protein oxidation and inflammation in adolescents with and at varying risk for BD type I (BD-I). Methods Blood was obtained from four groups of adolescents (9–20 years of age): (1) healthy comparison subjects with no personal or family history of psychiatric disorders (n = 13), (2) subjects with no psychiatric diagnosis and at least one parent with BD-I (‘high-risk’, n = 15), (3) subjects with at least one parent with BD-I and a diagnosis of depressive disorder not-otherwise-specified (‘ultra-high-risk’, n = 20), and (4) first-episode patients exhibiting mixed or manic symptoms that received a diagnosis of BD-I (n = 16). Plasma levels of lipid peroxidation (LPH, 4-HNE, 8-ISO), protein carbonyl, and inflammation (IL-1α-β, IL-6, IL-10, IFN γ TNFα) were assessed using analysis of variance and covariance models. Results LPH was lower in adolescents with fully syndromal BD than controls, while LPH levels in the at-risk groups were between healthy controls and fully syndromal BD. Post-hoc analysis showed a non-significant increase in the (4-HNE+8-ISO)/LPH ratio suggesting a potential conversion of LPH into late-stage markers of lipid peroxidation. There were no significant differences among protein carbonyl content and inflammatory markers. Conclusions In adolescents, fully syndromal BD is associated with significant reductions in LPH levels, and LPH levels decrease along the spectrum of risk for BD-I. Quantifying lipid peroxidation in longitudinal studies may help clarify the role of LPH in BD risk progression.

The ups and downs of cellular stress: the “MAM hypothesis” for Bipolar disorder pathophysiology

“…In addition, higher protein carbonyl and lipid hydroperoxide content were determined in adults compared to adolescents with BD [101] and the increased levels of an early component of the peroxidation chain in euthymic older patients with BD support the hypothesis of a persistent effect of ROS in patients with BD into late life [102]. It was observed in a recent exploratory study that the plasma levels of oxidative stress markers were lower in adolescents with fully syndromal BD than controls, while levels in the at-risk groups were between healthy controls and fully syndromal BD supporting a role of oxidative stress in BD risk progression [103]. Furthermore, Andreazza and colleagues observed that superoxide dismutase activity was higher in manic and depressed patients compared to euthymic patients and controls [104].…”

The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: Knowledge to date and directions for future research

“…244 A study of adolescents with or at risk for PBD found that adolescents with PBD had significantly lower LPH vs controls, with non-symptomatic adolescents at familial risk falling between the other groups. 245 Finally, a study of 29 adolescents with PBD and 25 HCs found that LPH−BDNF correlations were significantly different between adolescents with PBD and HCs, and that, among adolescents with PBD in the top half of the distribution of BDNF levels, greater LPH levels were associated with poorer executive function. 246 …”

Neurobiology of Risk for Bipolar Disorder

“…Most recently, plasma levels of lipid peroxidation (lipid hydroperoxide and 4-hydroxy-2-nonenal, 8-isoprostane), protein oxidation (protein carbonyls), and inflammation (interleukin 1, interleukin 6, interleukin 10, interferon gamma, TNF alfa) were assessed in four groups of adolescents (9–20 years of age), consisting of high-risk offspring, ultrahigh-risk offspring, first-episode BD patients, and healthy controls [90]. The levels of lipid hydroperoxide, an early stage lipid peroxidation marker, showed a decreasing trend along the spectrum of risk for BD-I, while there was no difference in the late stage lipid peroxidation markers (4-hydroxy-2-nonenal, 8-isoprostane), protein carbonyls, and inflammatory markers among groups [90].…”

“…The levels of lipid hydroperoxide, an early stage lipid peroxidation marker, showed a decreasing trend along the spectrum of risk for BD-I, while there was no difference in the late stage lipid peroxidation markers (4-hydroxy-2-nonenal, 8-isoprostane), protein carbonyls, and inflammatory markers among groups [90]. …”