- Also known as clinical [[depression]] - Common and serious mental disorder characterized by persistent low mood, loss of interest or pleasure in normally enjoyable activities (anhedonia), and impaired functioning - Typically involves at least two weeks of pervasive depressed mood or [[Anhedonia]], along with other emotional, cognitive, and physical symptoms - Significantly impacts personal, social, occupational, and physical health domains - Affects about 18% of people at some point in life, more common in women and younger adults - Diagnosis requires ruling out episodes of mania or hypomania to exclude bipolar disorder - Episodes can be single or recurrent, with varying severity (mild, moderate, severe) ## Signs and Symptoms - Persistent sadness, emptiness, or hopelessness - Loss of interest or pleasure in most activities - Feelings of worthlessness, excessive guilt, or self-blame - Difficulty concentrating, making decisions, or remembering things - Fatigue, lack of energy; slowed or agitated movements and speech - Sleep disturbances: insomnia, early awakening, or hypersomnia - Appetite or weight changes (loss or gain) - Irritability or frustration even over minor matters - Recurrent thoughts of death, suicidal ideation, or suicide attempts - Physical complaints such as headaches, digestive problems, or unexplained pain - In children and adolescents, may present as irritability or academic decline ## Clinical Features and Diagnosis - Diagnosis based on DSM-5 criteria requiring 5 or more symptoms present nearly every day for at least two weeks, with at least one being depressed mood or anhedonia - Subtypes ("specifiers") include melancholic, atypical, catatonic, with anxious distress, peripartum onset, and seasonal pattern - Severity impacts degree of social or occupational dysfunction - Can co-occur with anxiety disorders; anxiety can worsen prognosis and [[Suicide|suicide]] risk ## Causes and Risk Factors - Multifactorial: genetic, environmental, and [[Psychology|psychological]] components - Family history increases risk (~40% genetic contribution) - Triggers include major life changes, childhood [[trauma]], chronic medical conditions, substance use, and certain medications - Environmental factors like lead exposure may contribute ## Treatment and Management - Main treatments: [[psychotherapy]], antidepressant medications - Hospitalization required in severe cases with risk of harm or self-neglect - Other treatments include [[electroconvulsive therapy (ECT)]], [[ketamine]], esketamine, and [[psilocybin]] for treatment-resistant [[depression]] - Neurofeedback and attention-training interventions may be adjunctive - Ongoing research into individualized predictions of response and [[Brain Networks|brain network]] dysfunctions linked to MDD ## Impact - Second leading cause of disability worldwide by years lived with disability - Negatively affects work, school, relationships, and overall quality of life - High risk for recurrent episodes and chronicity without treatment - Contributes to cognitive and physical health complaints, increasing overall health burden