Major depressive disorder (MDD) is the most frequent cause of disability, affecting almost 16% of the world's population. Despite this, little is known about the condition's underlying mechanism. According to publicly available estimates from the World Health Organization (WHO), MDD is anticipated to be a significant contributor to disability globally by 2030. At any given time, depression affects 14 million Americans, or 10% of the country's total population.
Depressed mood (lack of drive or hope), anhedonia (lower capacity for pleasure-seeking behavior such as eating, sex, and social contacts), anergia, irritability, difficulties focusing, disturbed sleep, appetite, and cognition, and propensity toward suicide are the core symptoms of MDD. Not only are anxiety disorders and depression commonly co-morbid, but depression is also intimately linked to other conditions like dementia, type 2 diabetes, coronary artery disease, Parkinson's disease, epilepsy, pain, malignancies, ageing, osteoporosis, and irritable bowel syndrome. Unfortunately, the persistent and crippling nature of depression complicates the prognosis of many chronic illnesses and worsens the global situation of disease and incapacity (Dr. Hill).
The aetiologies of depression are not well cleared, despite the fact that this multifaceted and heterogeneous condition has received a lot of research. The genuine "depression genes," which are responsible for the onset and cure of depression and may be altered to produce models of depression in rodents, have not yet been identified by genetic study, but risk loci for many other common diseases have. However, it is still believed that a combination of external environmental factors (particularly stressful events like losing loved ones or employment) and hereditary factors (approximately 40%) have a role in the development of depression. Endocrine problems (hyper- or hypothyroidism), malignancies (such as pancreatic adenocarcinoma and breast cancers), and negative pharmacological side effects (such recombinant interferons) are among the environmental risk factors linked to depression.
The HPA axis (hypothalamic-pituitary-adrenal) and sympathetic nervous system may be activated as a result of stressful life experiences, causing a variety of psychological and physiological changes that are sometimes referred to as psychological stress responses. Here, we will provide a summary of recent methods and findings that shed light on the relationships between psychological stress and depression. Due to terrorism, conflict, divorce, and unemployment, psychological stress has become more prevalent in scientific works as well as in popular media like the internet, newspapers, and TV. An array of physiological reactions, including those of the neurological, endocrine, and immunological systems, can be brought on by psychological stress, which is an adaptation to the fight-or-flight response developed during evolution. According to studies conducted over the past 40 years, among these reactions, hyperactivity of the HPA axis is one of the neuro-biological changes that affect depressive patients the most frequently (HPA axis dysfunction is present in around 70% of patients with depression) (Dr. Stephan).
Psychological stresses can be divided into two categories based on how long they last: acute psychological stress (such as anxiety during a surgery or an exam) and chronic psychological stress (like worry about children, financial difficulties, or reoccurring headaches), which can be further divided into disconnected and persistent psychological stress. The limbic system transmits impulses from the upper cortical regions of the brain to the hypothalamus in reaction to psychological stress. The release of neurotransmitters including serotonin, nor-epinephrine (NE), and acetylcholine occurs along with the activation of specific paraventricular nucleus (PVN) cells in the hypothalamus that produce and secrete corticotrophin releasing factor (CRF). The corticotrophs at the anterior pituitary gland are then stimulated by CRF when it enters the hypothalamic portal venous system to produce proopiomelanocortin (POMC). The polyprotein POMC then splits to produce adreno-corticotropic hormone (ACTH) and alpha melanocyte-stimulating hormone (-MSH), just as proinsulin cleaves to produce insulin and C-peptide. The release of arginine vasopressin (AVP) from parvocellular neurons is likewise stimulated by CRF from parvo-cellular neurons, and AVP and CRF work synergistically to stimulate the release of ACTH (Dr Miller).
To create and release glucocorticoids (GCs, or cortisol and corticosterone in human and rodent, respectively), which together with catecholamine produced by the sympathetic nervous system (SNS) are the principal stress hormones, ACTH stimulates the zone fasciculate and reticularis of the adrenal cortex. GCs have an impact on a variety of elements of brain function, including immunology and peripheral processes like metabolism. These include the survival of neurons, neurogenesis, hippocampus size, and emotional events. These GCs inhibit the activity of the HPA axis through a negative feedback mechanism by interacting with glucocorticoid receptors (GRs) in the hypothalamus, pituitary, and medial prefrontal cortex (mPFC), which will lead to a reduction in CRF secretion and subsequently reduced release of ACTH from the pituitary.