Neurosteroids and Neurotrophic Factors: What Is Their Promise as Biomarkers for Major Depression and PTSD?

Abstract

Even though major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are among the most prevalent and incapacitating mental illnesses in the world, their diagnosis still relies solely on the characterization of subjective symptoms (many of which are shared by multiple disorders) self-reported by patients. Thus, the need for objective measures that aid in the detection of and differentiation between psychiatric disorders becomes urgent. In this paper, we explore the potential of neurosteroids and neurotrophic proteins as biomarkers for MDD and PTSD. Circulating levels of the GABAergic neuroactive steroid, allopregnanolone, are diminished in MDD and PTSD patients, which corroborates the finding of depleted neurosteroid levels observed in animal models of these disorders. The neurotrophic protein, brain-derived neurotropic factor (BDNF), is also reduced in the periphery and in the brain of MDD patients and depressed-like animals that express lower neurosteroid levels. Although the role of BDNF in PTSD psychopathology seems less clear and merits more research, we propose a causal link between allopregnanolone levels and BDNF expression that could function as a biomarker axis for the diagnosis of both MDD and PTSD.

Long Non-coding RNA LINC01119 Promotes Neuropathic Pain by Stabilizing BDNF Transcript

“…Our results also suggest that both LINC01119 and BDNF mRNA were interacted by ELAVL1 protein, however, the direct interaction between LINC01119 and BDNF mRNA were not observed, suggesting that ELAVL1 protein may function as a scaffold to form the LINC01119-ELAVL1-BDNF complex. Brain-derived neurotrophic factor (BDNF) is a well-studied growth factor that serves many critical functions within the central nervous system (Almeida et al, 2021). It is a member of a unique family of polypeptide growth factors, neurotrophies, which influence the proliferation, differentiation, survival, and death of neuronal and non-neuronal cells (Cappoli et al, 2020;Su et al, 2020).…”

Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics

“…It is important to emphasize that the dysregulation in basal and reactive HPA axis in PTSD is complex and may also involve a variety of steroid compounds, including the neuroactive steroids, such as dehydroepiandrosterone (DHEA), its sulphate ester dehydroepiandrosterone sulphate (DHEA-S), allopregnanolone and pregnanolone. Alterations in the synthesis of neuroactive steroids has been associated with increased PTSD symptoms in humans [ 141 , 142 , 143 ] and in animal studies [ 144 , 145 , 146 , 147 ]. A marked decrease in cerebrospinal (CSF) levels of allopregnanolone and its equipotent stereoisomer, pregnanolone has been found in women with PTSD, and is apparently due to a block in ALLO synthesis at 3α-HSD [ 141 ].…”

Effect of Allopregnanolone on Spatial Memory and Synaptic Proteins in Animal Model of Metabolic Syndrome

“…BDNF the neurotrophic factor that controls synaptic plasticity [ 52 , 53 ]. Several studies reported increased BDNF levels following Allopregnanolone administration [ 54 , 55 , 56 ].…”