A 33-year-old woman is brought to the physician by her husband because of persistent sadness for the past 2 months. During this period, she also has had difficulty sleeping and an increased appetite. She had similar episodes that occurred 2 years ago and 9 months ago that each lasted for 4 months. Between these episodes, she reported feeling very energetic and rested after 3 hours of sleep. She often went for long periods of time without eating. She works as a stock market trader and received a promotion 5 months ago. She regularly attends yoga classes on the weekends with her friends. On mental status examination, she has a blunted affect. She denies suicidal thoughts and illicit drug use. Which of the following is the most likely diagnosis?

Major depressive disorder with seasonal pattern

Major depressive disorder with atypical features

A 25-year-old woman comes to the physician because of sadness that started 3 weeks after her daughter was born. Her daughter is now 9 months old and usually sleeps through the night, but the patient still has difficulty staying asleep. She has not returned to work since the birth. She is easily distracted from normal daily tasks. She used to enjoy cooking, but only orders delivery or take-out now. She says that she always feels too exhausted to do so and does not feel hungry much anyway. The pregnancy of the patient's child was complicated by gestational diabetes. The child was born at 36-weeks' gestation and has had no medical issues. The patient has no contact with the child's father. She is not sexually active. She does not smoke, drink alcohol, or use illicit drugs. She is 157 cm (5 ft 1 in) tall and weighs 47 kg (105 lb); BMI is 20 kg/m2. Vital signs are within normal limits. She is alert and cooperative but makes little eye contact. Physical examination shows no abnormalities. Which of the following is the most likely diagnosis?

Depression with peripartum-onset

Disruptive mood dysregulation disorder

A 38-year-old man comes to the physician because of persistent sadness and difficulty concentrating for the past 6 weeks. During this period, he has also had difficulty sleeping. He adds that he has been “feeling down” most of the time since his girlfriend broke up with him 4 years ago. Since then, he has only had a few periods of time when he did not feel that way, but none of these lasted for more than a month. He reports having no problems with appetite, weight, or energy. He does not use illicit drugs or alcohol. Mental status examination shows a depressed mood and constricted affect. Which of the following is the most likely diagnosis?

Adjustment disorder with depressed mood

A 24-year-old woman comes to the physician because she feels sad and has had frequent, brief episodes of crying for the last month. During this period, she sleeps in every morning and spends most of her time in bed playing video games or reading. She has not been spending time with friends but still attends a weekly book club and continues to plan her annual family reunion. She stopped going to the gym, eats more, and has gained 4 kg (8.8 lb) over the past 4 weeks. Three weeks ago, she also started to smoke marijuana a few times a week. She drinks one glass of wine daily and does not smoke cigarettes. She is currently unemployed; she lost her job as a physical therapist 3 months ago. Her vital signs are within normal limits. On mental status examination, she is calm, alert, and oriented to person, place, and time. Her mood is depressed; her speech is organized, logical, and coherent. She denies suicidal thoughts. Which of the following is the most likely diagnosis?

Persistent Depressive Disorder (Dysthymia)

A 42-year-old female presents to her primary care provider for an annual checkup. She reports feeling sad over the past few months for no apparent reason. She has lost interest in swimming, which she previously found enjoyable. Additionally, she has had trouble getting a full night’s sleep and has had trouble concentrating during the day. She has lost 15 pounds since her last visit one year prior. Which of the following sets of neurotransmitter levels is associated with this patient’s condition?

Decreased norepinephrine, decreased serotonin, decreased dopamine

Decreased acetylcholine, normal serotonin, normal dopamine

Decreased GABA, decreased acetylcholine, increased dopamine

Increased norepinephrine, decreased serotonin, decreased GABA

Increased acetylcholine, increased serotonin, decreased dopamine

A previously healthy 56-year-old woman comes to the family physician for a 1-month history of sleep disturbance and sadness. The symptoms have been occurring since her husband died in a car accident. Before eventually falling asleep, she stays awake for multiple hours and has crying spells. Several times she has been woken up by the sound of her husband calling her name. She has lost 3 kg (6.6 lb) over the past month. She has 3 children with whom she still keeps regular contact and regularly attends church services with her friends. She expresses feeling a great feeling of loss over the death of her husband. She has no suicidal ideation. She is alert and oriented. Neurological exam shows no abnormalities. Which of the following is the most likely diagnosis for this patient's symptoms?

Adjustment disorder with depressed mood

Major depressive disorder diagnostic criteria for USMLE Step 3: High-Yield Psychiatry Lessons

MDD Dx Criteria - SIGECAPS in a Nutshell

Diagnosis requires ≥5 of 9 symptoms for ≥2 weeks, causing significant distress/impairment. One symptom must be (1) depressed mood or (2) anhedonia.

📌 SIGECAPS + Depressed Mood

Sleep: Insomnia or hypersomnia
Interest: ↓ Anhedonia (loss of interest or pleasure)
Guilt: Feelings of worthlessness, inappropriate guilt
Energy: ↓ Fatigue or loss of energy
Concentration: ↓ Diminished ability to think or concentrate
Appetite: ↓ or ↑, or weight change (>5% in 1 month)
Psychomotor: Agitation or retardation (observable by others)
Suicidal Ideation: Recurrent thoughts of death

⭐ Exam Favorite: MDD symptoms in the context of bereavement can still be diagnosed as MDD. The bereavement exclusion is no longer a strict rule if full criteria are met, especially with functional impairment or suicidal ideation.

Clinical Specifiers - Flavoring the Blues

With Anxious Distress: At least 2 symptoms like tension, restlessness, worry, or fear of losing control.
With Mixed Features: At least 3 manic/hypomanic symptoms present during depressive episodes.
With Atypical Features: Mood reactivity (brightens to positive events).
- 📌 CRASH: Carbohydrate craving/weight gain, Rejection sensitivity, Anhedonia-reversed, Sleep increase (hypersomnia), Heavy/leaden feelings.
With Melancholic Features: Severe anhedonia, lack of mood reactivity, depression worse in the morning, early morning awakening, significant weight loss.
With Psychotic Features: Delusions and/or hallucinations.
- Mood-congruent: Content aligns with depressive themes (guilt, death).
With Peripartum Onset: During pregnancy or within 4 weeks postpartum.
With Seasonal Pattern (SAD): Onset and remission at characteristic times of the year.

Mood state fluctuations in affective disorders

⭐ Atypical features are a classic predictor of preferential response to Monoamine Oxidase Inhibitors (MAOIs).

Exclusion Criteria - What It's Not

Symptoms are not better accounted for by:

Substance/Medication-Induced Depressive Disorder
- Not due to direct effects of drugs (e.g., alcohol, cocaine) or medications (e.g., steroids, interferon).
Depressive Disorder Due to Another Medical Condition
- Not a direct result of conditions like hypothyroidism, Huntington's, or traumatic brain injury.
Bipolar I or II Disorder
- Crucially, there has never been a manic or hypomanic episode.
Psychotic Disorders
- Not better explained by schizophrenia, schizoaffective disorder, or other primary psychotic illnesses.

Bipolar vs. Major Depressive Disorder Comparison

⭐ A single lifetime manic episode is sufficient to diagnose Bipolar I Disorder, which permanently rules out a diagnosis of MDD.

High‑Yield Points - ⚡ Biggest Takeaways

Core criteria: depressed mood or anhedonia (loss of interest/pleasure) is mandatory.

Requires ≥ 5 of 9 classic "SIGECAPS" symptoms for ≥ 2 weeks.

Symptoms must cause clinically significant distress or functional impairment.

Always rule out substance abuse or another medical condition as the primary cause.

Watch for key indicators like sleep disturbances, feelings of worthlessness, and fatigue.

Presence of suicidal ideation is a critical and high-yield diagnostic point.

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