Withania somnifera & GABA

The botanical known as Ashwagandha (Withania somnifera) is often used for its adaptogenic properties, which modulate general conditions like insomnia, stress, anxiety, and cognitive function. GABA is the inhibitory neurotransmitter in the central nervous system mediating pathological processes such as anxiety, depression, epilepsy, and other cognitive disorders.  The study completed by Candelario et al.(2015) aimed to examine the root extract of Ashwagandha and its constituents, and how they inhibit GABA receptors in the CNS. Results of the study suggest that the key constituents in Ashwagandha may beneficially influence the signaling dysfunction found in general anxiety disorders, sleep disorders, and cognitive disorders by targeting GABA in the CNS. 

Candelario M. et al.(2015) Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAa and GABAp receptors.  Journal of Ethnopharmacology, 171 (May 2015), 264-272. http://dx.doi.org/10.1016/j.jep.2015.05.058
   

Novel Mechanistic non-linear model & Circadian Oscillations of hormones in HPA-axis related to Depression

The etiology of depression is discussed in a study by Gudmand-Hoeyer et al. (2014).  While depression is associated with dysregulation of the HPA-axis many of the resulting hormones synthesized in this system are affected and downstream concentrations directly influence the energy in the brain and muscles. These hormones are synthesized at different rates and times during the day.  Utilizing a multi-scale modeling approach, this study was able to show both the circadian and ultradian oscillations of hormones as it is related to depression.  The three parameters varying between groups that were examined in this study reveal hypocortisolemic depressed, hypercortisolemic depressed, and non-depressed. The model utilized in this study allows for the complex interpretation of ACTH levels and the resulting synthesis of cortisol and associated depression. 

J. Gudmand-Hoeyer et al.(2014). Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations, Mathematical Biosciences, 257(September 2014), 23-32. http://dx.doi.org/10.1016/j.mbs.2014.07.013

Depression & HPA-Axis

Regulation of our internal environment involves three systems: the nervous system, immune system, and endocrine system. The hypothalamic-pituitary-adrenal (HPA) axis is integral to all three of these systems and is often disrupted and hyperactive in major depression (MD).  Neuroendocrine stimulation research suggests that negative coping strategies predicts the plasma cortisol response, which is controlled by the HPA-axis. Results of the study by N.Hohne et al.(2014) indicate that subjects with a lifetime history of major depression have HPA-axis dysregulation and negative coping strategies, compared to individuals that have never been depressed. 

N. Hohne et al.(2014). Increased HPA axis response to pyschosocial stress in remitted depression: the influence of coping style, Biological Psychology, 103 (September 2014), 265-267. http://dx.doi.org/10.1016/j.biopsycho.2014.09.008