Major Depressive Disorder

Overview

Major Depressive Disorder (MDD) is a serious mental health condition characterized by persistent sadness, loss of interest in activities, and a range of emotional and physical symptoms that significantly interfere with daily life. Unlike normal sadness or grief, depression is a pervasive condition lasting weeks, months, or years.

MDD affects more than 280 million people worldwide and is the leading cause of disability globally. In the United States, 21 million adults (8.4% of the population) experience at least one major depressive episode annually.

Symptoms

The DSM-5-TR requires five or more of the following symptoms to be present during the same two-week period, with at least one symptom being depressed mood or loss of interest:

• Depressed mood — feeling sad, empty, or hopeless most of the day, nearly every day
• Loss of interest or pleasure — markedly diminished interest in all or almost all activities
• Weight changes — significant weight loss or gain (>5% body weight in a month)
• Sleep disturbances — insomnia or hypersomnia nearly every day
• Psychomotor changes — agitation or retardation observable by others
• Fatigue — loss of energy nearly every day
• Worthlessness or guilt — feelings of worthlessness or excessive/inappropriate guilt
• Cognitive difficulties — diminished ability to think, concentrate, or make decisions
• Suicidal thoughts — recurrent thoughts of death, suicidal ideation, or suicide attempt

Causes & Risk Factors

Depression arises from a complex interaction of genetic, biological, environmental, and psychological factors.

Genetic Factors

Twin studies estimate heritability at approximately 40%, indicating moderate genetic contribution. First-degree relatives of individuals with MDD have a 2-3 times higher risk. Genome-wide association studies have identified over 100 genetic loci associated with depression risk.

Neurobiological Factors

Neuroimaging studies show structural and functional changes in depression:

• Reduced hippocampal volume (associated with stress and cortisol)
• Prefrontal cortex dysfunction (affecting emotion regulation)
• Amygdala hyperactivity (heightened negative emotional processing)
• Disrupted default mode network connectivity

Neurotransmitter Dysregulation

Environmental Risk Factors

• Childhood adversity — abuse, neglect, parental loss (2-3x increased risk)
• Chronic stress — work, financial, relational
• Trauma — physical or emotional traumatic events
• Social isolation — lack of social support
• Medical illness — chronic pain, cancer, cardiovascular disease, diabetes
• Substance use — alcohol, cannabis, stimulants

Epidemiology

• Prevalence: 8.4% of US adults (21 million) experience MDD annually
• Lifetime prevalence: Approximately 20% (1 in 5 people will experience depression in their lifetime)
• Gender: Women are twice as likely as men (10.5% vs 5.5%)
• Age: Highest rates in 18-25 age group (17.0%)
• Comorbidity: 75% of people with MDD have at least one other psychiatric disorder

Diagnosis

Clinical diagnosis involves structured interview, DSM-5-TR criteria assessment, and screening instruments:

• PHQ-9 (Patient Health Questionnaire-9) — Most widely used screening tool. Score ≥10 indicates moderate-to-severe depression.
• Hamilton Depression Rating Scale (HAM-D) — Clinician-administered, 17-21 items. Gold standard in research.
• Beck Depression Inventory (BDI-II) — 21-item self-report measuring severity.

Medical workup should rule out thyroid disorders, vitamin deficiencies (B12, D), anemia, and other conditions that can mimic depression.

When to Seek Help

Seek professional evaluation if:

• Symptoms persist for more than two weeks
• Depression interferes with work, relationships, or daily activities
• You have thoughts of self-harm or suicide
• You're using alcohol or drugs to cope