Serum BDNF levels in unaffected first-degree relatives of patients with bipolar disorder

Abstract

Objective: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls. Methods: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies. Results: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls. Conclusion: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

Neurobiology of Risk for Bipolar Disorder

“…Serum BDNF levels were found to be decreased [91] or unchanged [92, 93] in BD-P and BD-FDR compared to healthy controls. Duffy et al reported that the BDNF genotype significantly moderates the association between high-risk status for both gene expression and protein levels in BD offspring [88].…”

A review on shared clinical and biological aspects of bipolar disorder and frontotemporal dementia

“…This process involves dysfunctions in several systems, potentially affecting cellular resilience and neural plasticity (Berk et al, 2011;Grande et al, 2016;Vavakova et al, 2015). This vulnerability seems to be related to increased inflammation, where cytokines seem to play a role, as well as a number of modifications caused by increased oxidative stress, mitochondrial dysfunction and a decrease in neurotropic factors (Cunha et al, 2006;Fernandes et al, 2011;Gigante et al, 2011;Kapczinski et al, 2010;Kapczinski et al, 2008;Nery et al, 2016). The concept of neuroprogression in BD also reflects neurodegeneration in these patients.…”

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

“…The study by Nery et al 2 recently published in Revista Brasileira de Psiquiatria was the first to examine peripheral brain-derived neurotrophic factor (BDNF) levels in unaffected siblings of patients with BD. Their ultimate goal was to investigate whether abnormal expression of this neurotrophin might represent an endophenotype of illness, i.e., a quantitative trait that is intermediate between the disease phenotype and its underlying biological process.…”

“…2 This places the regulation of immune responses as an important target in the pathophysiology of schizophrenia and BD. In this context, it should be noted that melatonin plays an important role in the regulation of both immune and glial cell reactivity, including through its autocrine effects, which worldleading work by Markus et al in Brazil has shown.…”

“…However, a plethora of recent data shows that melatonin is synthesized in many, if not all, mitochondria-containing cells. 2 As such, the genetic associations of melatonin with BD are likely to be linked to changes in a wide array of organs and tissues, including the gut, as well as in glia and immune cell regulation. Likewise, the general decrease in pineal melatonin levels in schizophrenia is likely to represent alterations in central and peripheral sites, as well as in circadian regulation.…”