Depression Disease Background

Introduction

Depression is defined as a mood state indicating the absence of a positive affect or the feeling of sadness, despair, anxiety, discouragement or hopelessness. It is also defined as a mental disorder where depression is a manifestation (eg unipolar major depression, bipolar depression, minor depression or dysthymia, schizophrenia). 

Epidemiology

According to the World Health Organization (WHO), depression is estimated to affect 5% of adults globally and is a leading cause of disability. Approximately, 5.7% of adults >60 years are affected by depression. As of 2015, there are 322 million people living with depression, representing over 4% of the global population. Though the prevalence of depression varies by age, there is a noted peak during adulthood. It is also more common in women. It is also a major contributor to the overall global burden of disease and can result in poor functioning of an individual in various areas such as work, school and family life. Approximately 75% of affected individuals in low- and middle-income countries receive no treatment due to lack of resources, lack of trained healthcare providers and social stigma associated with mental disorders. At its worst, depression can lead to suicide. In 2015, 800,000 people died by suicide. Suicide is the second leading cause of death among 15- to 29-year-olds in 2015. Alarmingly, there is also a noted increase in prevalence of depression, with over an 18% increase between 2005 and 2015.

Depression is also the leading cause of disability in the South-East Asia Region, affecting 7% of the population. In South-East Asia, as much as 86 million people suffer from depression, with countries like Singapore and Malaysia having an overall prevalence of 6-12%.

Pathophysiology

Depression involves multiple factors including genetic, environmental, social, psychological, and neurobiological factors. It is believed to be related to the changes in neurotransmitter levels in the brain, particularly the neurotransmitters glutamate, γ-aminobutyric acid (GABA), serotonin, dopamine, and norepinephrine. All these neurotransmitters play a crucial role in regulating mood, emotion, and behavior. Patients with depression have been observed to have problems involving the hypothalamic-pituitary-adrenal (HPA) axis (eg hypercortisolemia and decreased rhythmicity). There is noted volumetric reductions in the hippocampus and other forebrain regions in patients with depression, supporting the contribution of decreasing neurotrophic factors that regulate neuronal plasticity in depression. Studies have also implicated the role of inflammation in depression. Treatment with antidepressants significantly decreased the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-10, and C-C motif ligand 2 chemokine. Recent studies have also linked the microbiota-gut-brain axis to the regulation of mood, behavior, and neuronal transmission, and its association with the development of depression. The gut microbiota can influence the brain through the HPA axis, neuroendocrine, autonomic, and neuroimmune systems.

Risk Factors

Depression results from a complex interaction between social, psychological, and biological factors. People who have gone through adverse life events (eg unemployment, bereavement, psychological trauma) are much more likely to develop depression. In turn, depression can lead to more stress and dysfunction, inevitably worsening the affected person's life situation and the depression itself. Lastly, hormonal factors may also play a role, contributing to the increased rate of depression seen in women.