Epigenetic Influences on Anxious and Depressive Behaviors: BDNF Links

The identification of genetic biomarkers facilitates the staging of brain disorders, their prognosis, choice of treatments and interventions, prediction of response, and prognosis of outcomes over a wide spectrum of symptoms associated with affective states, possibly optimizing clinical practice treatments and procedures. In this regard, epigenetic mechanisms mediate the effects of the environment on human-animal neurodevelopment of behavioral repertoires and imply also that employing the sensitivity of laboratory animals to environmental cues may be applied usefully for the consideration of long-term health and welfare of individuals [26]. Epigenetic mechanisms regulating primary brain signals, e.g., serotonin, noradrenaline and hypothalamic-pituitary-adrenal axis functioning, as well as factors governing neurotransmitter metabolism seem implicated in the participation of neurotrophic factors that are indispensable for neurogenesis, survival, restoration and functional maintenance of ongoing brain systems, structurally and functionally [2]. The maladaptive response to stress-induced hypothalamic-pituitary-adrenal (HPA) axis dysregulation, over neurodevelopmental phases but most especially during earlylife, consisting of exposure to glucocorticoids and stress in various forms, durations, and intensities gives rise to persistent epigenetic changes in the function of HPA axis-associated genes that govern homeostatic levels of glucocorticoids thereby focusing genes for brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase (TH) intimately involved in healthy and unhealthy affective conditions [6,19]. Greater levels of BDNF promoter methylation status, an emerging genetic biomarker for mood dysfunction, were associated significantly with a history of earlier suicidal attempt, suicidal ideation during treatment, and suicidal ideation during final evaluation in addition to higher Beck Scale for suicide ideation scores as well as poorer treatment outcomes for suicidal ideation [16]. Nevertheless, the influence of physical exercise as an intervention to alleviate symptoms and biomarkers of anxiety and depressiveness, accompanied by an increase in BDNF, has been shown to offer several benefits [1,27].