Major Depressive Disorder

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MDD Basics - Deep Dive Diagnosis

  • Definition: Persistent low mood or anhedonia causing significant distress/impairment; common, often recurrent.
  • DSM-5 Criteria: $\ge$ 5 of 9 symptoms in same 2-week period; must include (1) depressed mood or (2) anhedonia (loss of interest/pleasure).
    • 📌 SIGECAPS:
      • Sleep disturbance (insomnia/hypersomnia)
      • Interest decreased (anhedonia)
      • Guilt or worthlessness
      • Energy decreased (fatigue)
      • Concentration difficulties
      • Appetite change (↑/↓) or weight change ($\ge$ 5%/month)
      • Psychomotor agitation/retardation
      • Suicidal ideation/thoughts
  • Symptoms cause clinically significant distress or functional impairment.
  • Not attributable to substance use or another medical condition. Episode not better explained by a psychotic disorder. No history of manic/hypomanic episode.

⭐ MDD is approximately twice as common in women as in men, a finding consistent across many cultures and countries.

Etiopathogenesis - Brain's Blue Notes

  • Biological Factors:
    • Monoamine Hypothesis: ↓ Serotonin (5-HT), ↓ Norepinephrine (NE), ↓ Dopamine (DA).
    • Neuroendocrine:
      • Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity: ↑ Cortisol; Dexamethasone Suppression Test (DST) non-suppression.
      • Thyroid dysfunction (e.g., hypothyroidism).
    • Neuroinflammation: ↑ Pro-inflammatory cytokines (e.g., IL-6, TNF-α).
    • Genetics:
      • Heritability approx. ~37%.
      • Gene-environment interaction (e.g., 5-HTTLPR polymorphism & stress).
    • Brain Structural & Functional Changes: ↓ Hippocampal volume; altered Prefrontal Cortex (PFC), amygdala, Anterior Cingulate Cortex (ACC) activity. Coronal MRI showing hippocampal atrophy in MDD
  • Psychosocial Factors:
    • Stressful life events (e.g., loss, trauma, abuse).
    • Early life adversity.
    • Personality traits (e.g., neuroticism, introversion).
    • Cognitive theory (Beck's cognitive triad: negative view of self, world, future).

⭐ HPA axis dysregulation, particularly hypercortisolemia and non-suppression on the Dexamethasone Suppression Test (DST), is a well-documented biological finding in many patients with MDD.

Clinical Features & Diagnosis - Symptom Spotlight

  • Core Criteria (DSM-5):5 of 9 symptoms for ≥2 weeks; must include (1) depressed mood OR (2) anhedonia.
  • 📌 SIGECAPS Mnemonic:
    • Sleep disturbance (↑/↓)
    • Interest loss (↓, anhedonia)
    • Guilt (excessive, worthlessness)
    • Energy loss (↓, fatigue)
    • Concentration difficulties (↓, indecisiveness)
    • Appetite change (↑/↓, weight change >5%/month)
    • Psychomotor agitation/retardation (observable)
    • Suicidal thoughts/ideation
  • Key Exclusions: Symptoms not due to substance, other medical condition, or better explained by other psychotic disorders. Crucially, no history of mania/hypomania.
  • Common Specifiers:
    • Atypical features (mood reactivity, weight gain, hypersomnia, leaden paralysis, rejection sensitivity)
    • Melancholic features (severe anhedonia, early morning awakening, diurnal variation worse AM, guilt)
    • Psychotic features (delusions/hallucinations)
    • Anxious distress

⭐ MDD with psychotic features often requires combination treatment with an antidepressant and an antipsychotic, or Electroconvulsive Therapy (ECT).

Management - Mood Menders

  • Principles: Stepped care; aim for remission. Combine pharmacotherapy & psychotherapy.
  • Pharmacotherapy:
    • SSRIs (e.g., Fluoxetine): 1st line; SEs: GI, sexual.
    • SNRIs (e.g., Venlafaxine).
    • TCAs (e.g., Amitriptyline): Cardiotoxic, anticholinergic.
    • MAOIs (e.g., Phenelzine): Hypertensive crisis risk.
    • Augment/switch if poor response.
  • Psychotherapy: CBT, IPT.
  • Somatic Therapies:
    • ECT: Severe, treatment-resistant, psychotic MDD, catatonia, high suicide risk.
    • rTMS: For non-response.
  • Duration: Continue antidepressants 6-9 months post-remission.

⭐ ECT is the most effective treatment for severe MDD, especially with psychotic features or high suicide risk. It is considered the safest psychotropic intervention during pregnancy.

High‑Yield Points - ⚡ Biggest Takeaways

  • Core symptoms: Depressed mood or anhedonia for ≥2 weeks is essential for diagnosis.
  • Use SIGECAPS mnemonic for common associated symptoms.
  • SSRIs (e.g., Fluoxetine, Escitalopram) are first-line pharmacotherapy.
  • ECT is indicated for severe/treatment-resistant depression, active suicidality, or catatonia.
  • Key risk factors include female gender, family history, and stressful life events.
  • Suicide risk assessment is paramount in all patients with MDD.
  • Differentiate from Persistent Depressive Disorder (chronic depression, ≥2 years).

Practice Questions: Major Depressive Disorder

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What is the definition of "double depression" in the context of mental health?

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Flashcards: Major Depressive Disorder

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There is a(n) _____ in the activity of the prefrontal cortex during a cognitive activity in depression

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There is a(n) _____ in the activity of the prefrontal cortex during a cognitive activity in depression

decrease

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