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 male comes into the psychiatric clinic complaining of consistent sadness. He endorses feelings of worthlessness, anxiety, and anhedonia for the past couple months but denies feeling suicidal. He further denies any past episodes of feeling overly energetic with racing thoughts. Confident of the diagnosis, you recommend frequent talk therapy along with a long-term prescription of a known first-line medication for this disorder. What is the drug and what are some of the most frequently encountered side effects?

Selective serotonin reuptake inhibitor; anorgasmia, insomnia

Selective serotonin reuptake inhibitor; hypomania, suicidal thoughts

Tricyclic antidepressants; hypomania, suicidal thoughts

Monoamine oxidase inhibitors; Orthostatic hypotension, weight gain

Tricyclic antidepressants; Orthostatic hypotension, anticholinergic effects

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 27-year-old man comes to the physician for a follow-up examination. Paroxetine therapy was initiated 6 weeks ago for a major depressive episode. He now feels much better and says he is delighted with his newfound energy. He gets around 8 hours of sleep nightly. His appetite has increased. Last year, he had two episodes of depressed mood, insomnia, and low energy during which he had interrupted his job training and stopped going to the gym. Now, he has been able to resume his job at a local bank. He also goes to the gym three times a week to work out and enjoys reading books again. His temperature is 36.5°C (97.7°F), pulse is 70/min, and blood pressure is 128/66 mm Hg. Physical and neurologic examinations show no abnormalities. On mental status examination, he describes his mood as "good." Which of the following is the most appropriate next step in management?

Continue paroxetine therapy for 2 years

Switch from paroxetine to venlafaxine therapy

Continue paroxetine therapy for 6 months

Switch from paroxetine to lithium therapy

A 32-year-old woman presents with abdominal pain. She says that she has been experiencing a mild ‘tummy ache’ for about a week. On further questioning, the physician finds that she has been struggling to cope with her daily activities for the past month. She says that she is sad on most days of the week and doesn’t have much motivation to get up and do anything. She has difficulty concentrating and focusing on her job and, on many occasions, doesn’t have the urge to wake up and go to work. She has observed that on certain days she sleeps for 10-12 hours. She attributes this to the heaviness she feels in her legs which make it very difficult for her to get out of bed. Lately, she has also noticed that she is eating more than usual. Which of the following would most likely be another characteristic of this patient’s condition?

Inability to participate in social events she is invited to

An increased frequency of symptoms during winter

Guilt related to the way she treats others

A belief that people are secretly out to sabotage her

A 40-year-old man with a past medical history of major depression presents to the clinic. He is interested in joining a research study on depression-related sleep disturbances. He had 2 episodes of major depression within the last 2 years, occurring once during the summer and then during the winter of the other year. He has been non-compliant with medication and has a strong desire to treat his condition with non-pharmacological methods. He would like to be enrolled in this study that utilizes polysomnography to record sleep-wave patterns. Which of the following findings is likely associated with this patient’s psychiatric condition?

Associated with a seasonal pattern

A 24-year-old woman presents to her primary care physician for a wellness exam. She currently has no acute concerns but has been feeling hopeless, has a poor appetite, difficulty with concentration, and trouble with sleep. She says that she has poor self-esteem and that her symptoms have been occurring for the past 3 years. She has had moments where she felt better, but it lasted a few weeks out of the year. She currently lives alone and does not pursue romantic relationships because she feels she is not attractive. She has a past medical history of asthma. Her mother is alive and healthy. Her father committed suicide and suffered from major depressive disorder. On physical exam, the patient has a gloomy demeanor and appears restless and anxious. Which of the following is the most likely diagnosis?

Disruptive mood dysregulation disorder

A 32-year-old man comes to the physician because of a 2 month history of difficulty sleeping and worsening fatigue. During this time, he has also had difficulty concentrating and remembering tasks at work as well as diminished interest in his hobbies. He has no suicidal or homicidal ideation. He does not have auditory or visual hallucinations. Vital signs are normal. Physical examination shows no abnormalities. Mental status examination shows a depressed mood and flat affect with slowed thinking and speech. The physician prescribes sertraline. Three weeks later, the patient comes to the physician again with only minor improvements in his symptoms. Which of the following is the most appropriate next step in management?

Continue sertraline for 3 more weeks

Augment with aripiprazole and continue sertraline

Provide electroconvulsive therapy

Change medication to duloxetine

Augment with phenelzine and continue sertraline

Seasonal affective disorder — USMLE Lesson

Overview & Epidemiology - The Winter Blues

A subtype of Major Depressive Disorder (MDD) with a recurring seasonal pattern, typically starting in fall/winter and remitting in spring.
Linked to reduced sunlight exposure, which impacts circadian rhythms, serotonin, and melatonin levels.
Epidemiology:
- Affects ~5% of the U.S. population; more common in northern latitudes.
- Higher prevalence in women (F:M ratio ≈ 4:1).
- Typical age of onset is between 20-30 years.

⭐ For diagnosis, the seasonal depressive episodes must have occurred for at least 2 consecutive years, with seasonal episodes substantially outnumbering non-seasonal episodes over a lifetime.

Pathophysiology - Brain's Hibernation

Circadian Rhythm Disruption: Reduced sunlight exposure in autumn/winter disrupts the suprachiasmatic nucleus (SCN) of the hypothalamus.
Neurotransmitter Imbalance:
- ↑ Melatonin: Leads to lethargy and hypersomnia. The brain misinterprets dim light as a signal for prolonged nighttime.
- ↓ Serotonin (5-HT): Contributes to mood changes and carbohydrate cravings.

Circadian rhythm and melatonin regulation in SAD

⭐ Phase-Delay Hypothesis: A key theory suggests that in SAD, the circadian rhythm is delayed relative to the external clock, causing a mismatch between sleep-wake cycles and other bodily rhythms.

Diagnosis & Features - Spotting the Slump

Meets full criteria for Major Depressive Disorder (MDD) with a recurring seasonal pattern.
Key diagnostic timing:
- Onset and remission occur at characteristic times of the year for at least 2 consecutive years.
- Seasonal episodes must substantially outnumber any non-seasonal episodes.
Predominantly atypical depressive features:
- ↓ Energy (anergia) & leaden paralysis
- Hypersomnia (oversleeping)
- ↑ Appetite with carbohydrate craving
- Weight gain

📌 WINTER Mnemonic: Weight gain, Irritability, No energy, Tiredness, Eating carbs, Rejection sensitivity.

Seasonal Affective Disorder: Seasonal Mood Changes

⭐ To diagnose, the seasonal pattern must be observed for at least 2 years, with seasonal episodes being far more common than non-seasonal ones throughout the patient's life.

Management - Let There Be Light

First-Line Therapies:
- Light Therapy: Core treatment.
  - 10,000-lux broad-spectrum white light.
  - Daily morning exposure for 30-45 minutes.
  - Mechanism: ↓ melatonin, realigns circadian rhythm.
  - Side effects: Headaches, eye strain, nausea.
- Cognitive Behavioral Therapy for SAD (CBT-SAD):
  - Efficacy matches light therapy; longer-lasting effects.
  - Targets negative thoughts & behavioral inactivation.
Second-Line / Adjunctive:
- SSRIs (e.g., Fluoxetine, Sertraline) or Bupropion.
- Consider starting prophylactically in early autumn.

⭐ High-Yield: Screen for bipolar disorder before initiating light therapy, as it can precipitate hypomania/mania.

Woman using a light therapy box for SAD treatment

High‑Yield Points - ⚡ Biggest Takeaways

Seasonal Affective Disorder (SAD) is a subtype of major depressive disorder with a recurring seasonal pattern.

Episodes typically begin in the fall or winter and remit in the spring, occurring for at least 2 consecutive years.

Key features include atypical depressive symptoms like hypersomnia, increased appetite or weight gain, and carbohydrate craving.

Pathophysiology is linked to circadian rhythm disruption and altered melatonin metabolism.

First-line treatment is bright light therapy (phototherapy).

SSRIs and bupropion are effective pharmacotherapies.

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