Peripheral biomarkers in bipolar disorder: a population-based study in young adults

Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative disease that leads to the motor neurons depletion in the spinal cord anterior horn and pyramidal tract. Several evaluations have been proposed in order to provide a better follow-up and management of secondary complications. However, the biggest difficulty is to select a single instrument to objectively assess the neurological deficit, the ABsTRACT Objective: The aim of this study was to confirm, in a sample of young adults from the general population, recent findings regarding the pathophysiology of bipolar disorder. The focus of this investigation was finding group differences in one neurotrophin, two markers of oxidative damage, two proinflammatory cytokines and one anti-inflammatory cytokine in participants with bipolar disorder, major depression and people without any mood episodes. Markers assessed here were brain-derived neurotrophic factor (BDNF), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Method: Individuals from the general population, previously included in a cross-sectional study (n=1560), with a positive screen for bipolar disorder were recruited, as well as two groups of controls. One had only depressive episodes and the other had no history of mood episodes. This yielded a sample of 231 participants that further underwent diagnostic confirmation with the Structured Clinical Interview for DSM-IV (SCID). All analyses included a check for bivariate associations, as well as an a priori multivariate model with sex, social class, current mood state, use of substances and SCID diagnoses as predictors. Results: The final sample included 55 participants with bipolar disorder, 82 with major depression and 94 healthy controls. Only a minority was using any psychiatric medications (9.6%). Bipolar disorder was associated with higher PCC and TNF-α levels when compared to the control group. Major depression was also associated with higher PCC levels when compared to the control condition. Use of psychiatric medication was associated with lower TNF-α levels. Correlations between the same markers were not as strong as in clinical samples. Conclusions: Two broad conclusions are called for from these results. The first is that early-stage bipolar disorder is already associated with a pro-oxidant, proinflammatory state. The second is that these changes appear more subtle than those observed in typical late-stage, chronic patients, supporting the notion that a form of illness progression takes place. The main caveat is that these data are cross-sectional, not longitudinal, which precludes causal inferences as factors other than the bipolar illness can conceivably induce systemic toxicity.