What Is Depression?

Medically Reviewed and Compiled by Dr. [Adam N. Khan], MD.

Quick Clinical Definition

Depression, clinically termed major depressive disorder (MDD), is a common and serious mood disorder characterized by persistent sadness, loss of interest or pleasure, and impaired daily functioning. It affects emotional, cognitive, behavioral, and physical domains and can significantly increase morbidity and mortality if untreated.

Introduction: Understanding Depression

Depression is a leading cause of disability worldwide. It is not simply occasional sadness but a sustained clinical condition that affects thought patterns, behavior, and physical health. Globally, over 280 million people are affected by depressive disorders, with significant social, occupational, and health-related consequences.

Clinically, depression is heterogeneous, often coexisting with anxiety, chronic medical illnesses, and substance use disorders. Understanding its pathophysiology, risk factors, and treatment strategies is essential for optimal patient care.

Types of Depression

1. Major Depressive Disorder (MDD)

• Persistent depressed mood for at least two weeks
• Loss of interest or pleasure in activities
• Functional impairment

2. Persistent Depressive Disorder (Dysthymia)

• Chronic depressive symptoms lasting ≥2 years
• Lower intensity than MDD but functionally significant

3. Bipolar Depression

• Depressive episodes occurring within bipolar disorder
• Alternates with manic or hypomanic episodes

4. Seasonal Affective Disorder (SAD)

• Depression occurring seasonally, typically in winter
• Related to light exposure and circadian rhythm

5. Postpartum Depression

• Occurs after childbirth
• Affects maternal-infant bonding and maternal functioning

6. Atypical Depression

• Mood reactivity preserved
• Associated with hypersomnia, hyperphagia, and leaden paralysis

Core Symptoms of Depression

Emotional and Cognitive Symptoms

• Persistent sadness, emptiness, or irritability
• Feelings of guilt, worthlessness, or hopelessness
• Impaired concentration and decision-making
• Suicidal ideation or self-harm thoughts

Physical and Behavioral Symptoms

• Fatigue and low energy
• Sleep disturbances (insomnia or hypersomnia)
• Appetite and weight changes
• Psychomotor agitation or retardation
• Social withdrawal and loss of motivation

Functional Impairment

• Occupational underperformance
• Academic difficulties
• Strained interpersonal relationships
• Reduced quality of life

Causes and Risk Factors

Biological Factors

• Genetic predisposition: family history increases risk
• Neurotransmitter dysregulation: serotonin, norepinephrine, dopamine
• Neuroendocrine alterations: HPA axis hyperactivity, cortisol dysregulation
• Inflammatory pathways: chronic systemic inflammation linked to depression

Psychological Factors

• Negative cognitive styles (e.g., rumination, pessimism)
• Low self-esteem or maladaptive coping strategies
• Childhood adversity or trauma

Social and Environmental Factors

• Chronic stress or major life events
• Social isolation or poor support networks
• Socioeconomic hardship or unemployment

Medical and Comorbid Conditions

• Chronic pain, cardiovascular disease, diabetes
• Neurological disorders (stroke, Parkinson’s disease)
• Substance use disorders
• Postpartum or perimenopausal hormonal changes

Neurobiology of Depression

Brain Structures

• Prefrontal cortex: reduced activity associated with impaired executive function
• Amygdala: hyperactivity linked to negative emotion processing
• Hippocampus: volume reduction related to chronic stress

Neurotransmitters

• Serotonin: mood regulation, sleep, appetite
• Norepinephrine: arousal, energy, stress response
• Dopamine: reward processing, motivation

Neuroplasticity

• Chronic depression associated with impaired neurogenesis and synaptic connectivity
• Antidepressants and therapy promote neuroplasticity

Diagnosis of Depression

Clinical Assessment

• Structured psychiatric interview
• Symptom duration, severity, and functional impact
• Screening for suicidal ideation and safety

Diagnostic Tools

• PHQ-9 (Patient Health Questionnaire-9)
• Hamilton Depression Rating Scale (HAM-D)
• Beck Depression Inventory (BDI)

Differential Diagnosis

• Bipolar disorder (depressive vs. manic episodes)
• Generalized anxiety disorder
• Substance-induced mood disorders
• Medical conditions: hypothyroidism, anemia, chronic pain

Unique Clinical Takeaways

1. Depression and Physical Health

Chronic depression increases risk for cardiovascular disease, diabetes, and immune dysregulation.

Actionable insight: Screening for depression in patients with chronic medical illnesses improves overall prognosis and reduces morbidity.

2. Cognitive Distortions and Functional Disability

Depressed patients often experience pervasive cognitive biases affecting decision-making and workplace performance.

Actionable insight: Cognitive remediation therapy and structured cognitive-behavioral interventions can improve occupational and academic outcomes.

3. Heterogeneity in Treatment Response

Not all patients respond to first-line antidepressants; biological, psychological, and social factors influence treatment efficacy.

Actionable insight: Personalized treatment plans integrating psychotherapy, pharmacotherapy, and lifestyle modification optimize outcomes.

4. Early-Life Stress and Lifelong Vulnerability

Childhood trauma and adverse experiences are strong predictors of recurrent depressive episodes.

Actionable insight: Early identification and trauma-focused interventions reduce recurrence and severity.

Evidence-Based Treatment of Depression

Psychotherapy

Cognitive Behavioral Therapy (CBT)

• Targets negative thoughts and behaviors
• Effective for mild to moderate depression

Interpersonal Therapy (IPT)

• Focuses on relationship and role transitions
• Improves social functioning

Mindfulness-Based Cognitive Therapy

• Reduces relapse risk
• Enhances emotional regulation

Pharmacologic Treatment

First-Line Medications

• SSRIs (e.g., sertraline, escitalopram)
• SNRIs (e.g., venlafaxine, duloxetine)

Second-Line or Augmentation

• Atypical antidepressants (bupropion, mirtazapine)
• Psychotherapy augmentation
• Electroconvulsive therapy (ECT) for severe or treatment-resistant depression

Lifestyle and Non-Pharmacologic Interventions

• Regular physical exercise
• Sleep hygiene and circadian rhythm optimization
• Nutritional support
• Stress management and relaxation techniques
• Social engagement and support networks

Depression Across the Lifespan

Children and Adolescents

• Irritability more prominent than sadness
• School refusal and academic decline
• Early intervention improves long-term outcomes

Adults

• Chronic stressors and work-life imbalance
• Comorbid anxiety and substance use
• Functional impairment in personal and professional domains

Older Adults

• Often underdiagnosed due to comorbid medical conditions
• Cognitive changes can mask depressive symptoms
• Pharmacologic sensitivity requires careful dosing

Prognosis

• Untreated depression is associated with chronicity, functional impairment, and increased suicide risk.
• Early diagnosis and evidence-based treatment improve remission rates.
• Relapse prevention strategies, including maintenance therapy and psychotherapy, are essential for long-term management.

Prevention and Early Detection

• Routine screening in primary care
• Psychoeducation for at-risk populations
• Early intervention for childhood adversity
• Integration of lifestyle interventions and social support

When to Seek Medical Care

• Persistent sadness or irritability for >2 weeks
• Loss of interest or pleasure in daily activities
• Functional impairment in work, school, or relationships
• Thoughts of self-harm or suicide

Immediate evaluation is required for suicidal ideation or self-harm behaviors.

Frequently Asked Questions

Medical Disclaimer

This article is intended for educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Clinical decisions should be made by qualified healthcare professionals based on individual patient assessment.