Major Depressive Disorder (MDD) Epidemiology and Pathophysiology
📌 MDD affects females more than males, with an average age of onset in the early 20s and a significant genetic association.
🧠 The Monoamine Hypothesis suggests MDD results from the depletion of monoamines, specifically serotonin (5HT), norepinephrine (NE), and dopamine (DA), supported by the effectiveness of drugs that increase these neurotransmitters (e.g., SSRIs).
⚖️ The Stress Diathesis Model proposes that MDD arises when genetic predispositions are activated by significant environmental stressors.

DSM-5 Criteria for MDD
⏱️ Symptoms must be present for at least two weeks (contrasted with mania, which requires one week—"two blue weeks" for depression).
⭐ Diagnosis requires at least five SIGECAPS symptoms to be present for the required duration.
😴 SIGECAPS mnemonic components: Sleep, Interest (decreased), Guilt, Energy (decreased), Concentration, Appetite, Psychomotor retardation, and Suicidality.
🌗 Typical/Melancholic depression involves decreased sleep (insomnia) and decreased appetite, whereas atypical depression involves sleeping too much and increased appetite.

Differential Diagnoses for Depressive Symptoms
🔄 Depression in Bipolar I or II Disorder must be differentiated, as symptoms can mirror MDD.
⏳ Dysthymia (Persistent Depressive Disorder) is characterized by at least two years of depressive symptoms, but with fewer than five SIGECAPS symptoms met.
💊 Substance-induced depression often occurs during withdrawal from stimulants (like cocaine or methamphetamine), where the withdrawal state is the opposite of the intoxication state (e.g., stimulant intoxication is high energy; withdrawal is depression).
👤 Schizoaffective disorder (depressed type) involves psychosis that occurs only when the patient is depressed, contrasting with MDD with psychotic features, where psychosis only occurs during depressive episodes.

Treatment: SSRI Mechanism
💊 The first-line treatment for depression involves medications such as SSRIs (Selective Serotonin Reuptake Inhibitors) and SNRIs.
🔬 SSRIs work by inhibiting the serotonin reuptake channel located on the presynaptic neuron.
🌊 Blocking reuptake causes serotonin to remain in the synapse, continuously activating the postsynaptic serotonin receptor, thus alleviating depressive symptoms.
⬆️ SNRIs function similarly but block both the serotonin and norepinephrine reuptake channels.

Key Points & Insights
➡️ To meet MDD criteria, patients need $\ge 5$ SIGECAPS symptoms for a minimum duration of two weeks ("two blue weeks").
➡️ Differentiating typical vs. atypical depression hinges on the presence of hypersomnia/hyperphagia (atypical) versus insomnia/anorexia (typical).
➡️ SSRIs increase synaptic serotonin concentration by preventing its reuptake into the presynaptic neuron, sustaining receptor stimulation.

📸 Video summarized with SummaryTube.com on Jan 17, 2026, 14:03 UTC