Functional Biomarkers of Depression: Diagnosis, Treatment, and Pathophysiology

Abstract

Major depressive disorder (MDD) is a heterogeneous illness for which there are currently no effective methods to objectively assess severity, endophenotypes, or response to treatment. Increasing evidence suggests that circulating levels of peripheral/serum growth factors and cytokines are altered in patients with MDD, and that antidepressant treatments reverse or normalize these effects. Furthermore, there is a large body of literature demonstrating that MDD is associated with changes in endocrine and metabolic factors. Here we provide a brief overview of the evidence that peripheral growth factors, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of MDD and antidepressant response. Recent preclinical studies demonstrating that peripheral growth factors and cytokines influence brain function and behavior are also discussed along with their implications for diagnosing and treating patients with MDD. Together, these studies highlight the need to develop a biomarker panel for depression that aims to profile diverse peripheral factors that together provide a biological signature of MDD subtypes as well as treatment response.

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

“…Although it is now firmly established that BDNF signaling plays an important role in the mechanism of action of antidepressant drugs, yet the role of BDNF in the pathophysiology of depression is less clear (Castren and Rantamaki, 2010). Furthermore, there is strong evidence that peripheral growth factors, including BDNF, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of major depressive disorder and antidepressant response (Schmidt et al, 2011). As a matter of fact BDNF levels are decreased in the blood of depressed patients and can be normalized with successful antidepressant treatment (Sen et al, 2008), although the origin and role of serum BDNF is unclear (Karege et al, 2005).…”

Personalized medicine in major depressive disorder — Opportunities and pitfalls

“…The constellation of symptoms also varies across patients. This hampers diagnosis and suggests that MDD is a heterogeneous disorder with possibly clinically distinct subpopulations or endophenotypes [11]. As no biologically based diagnostic tests are available, the subtypes of depression (e.g., seasonal affective disorder, postpartum, etc.)…”

“…The association between these various biochemical domains and MDD has sparked interest in the development of a serum-based, multi-analyte biomarker panel utilizing a composite score rather than the traditional single analyte approach. Such panels remain under development [11,24].…”

A review of the relationship between proinflammatory cytokines and major depressive disorder

“…Critically, research into the etiology of MDD needs to take into account the heterogeneous nature of the illness, and requires the development of methods by which to characterize and assess objectively severity of depression, response to treatment, and to classify MDD into its different subtypes (Schmidt et al, 2011). In this respect, central nervous system (CNS) inflammation has been suggested to play a significant role in MDD pathogenesis due to findings of increased proinflammatory cytokines levels in patients with neurodegeneration and symptoms of depression such as anhedonia, depressed mood, and lethargy .…”