USMLE® Step 1 Question of the Day: Depression

This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today's case focuses on a 38-year-old man who got laid off from work and could no longer concentrate long enough to write poems, which he loved doing in the past, decreased in appetite, and has difficulty going back to sleep. Can you figure it out?

A 38-year-old man comes to a clinic for evaluation of low energy and fatigue. He has been stressed since being laid off from work 6 months ago, but he feels he has no motivation to look for new employment. He used to write poetry, but he no longer enjoys it, stating, “I just can’t concentrate long enough to write anything of substance, and every time I try my mind wanders.” His appetite has also decreased, and he has lost 5.4-kg (12-lb) over this time. He awakes early in the morning and has difficulty going back to sleep. Vitals are within normal limits. Physical examination reveals a guarded adult male with slow speech. Which of the following abnormalities is most likely present in this patient?

A. Increased REM sleep latency

B. Decreased serum levels of c-reactive protein

C. Decreased neural transmission of monoamines

D. Increased hippocampal volume

E. Decreased serum cortisol

Scroll down to find the answer!

The correct answer to today's USMLE® Step 1 Question is...

C. Decreased neural transmission of monoamines

Before we get to the Main Explanation, let's look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

The incorrect answers to today's USMLE® Step 1 Question are...

A. Increased REM sleep latency

Incorrect: Depression can significantly alter sleep architecture; changes include decreased rapid eye movement sleep latency and slow-wave sleep.

B. Decreased serum levels of c-reactive protein

Incorrect: Hormonal and inflammatory factors have been suggested as potentially influencing a depressive state and depressive symptoms, which explains why many patients with unipolar major depression have increased mean serum levels of peripheral inflammatory markers such as cytokines and c-reactive protein.

D. Increased hippocampal volume

Incorrect: Depressive episodes are associated with higher levels of cortisol, which has been associated with damage to hippocampal neurons followed by atrophy. Some studies suggest that reduced hippocampal volumes precede the onset of depression.

E. Decreased serum cortisol

Incorrect: An indicator of chronic stress is elevated HPA-axis activity, typically measured by the presence of elevated serum cortisol levels. Increased, not decreased, serum cortisol levels have been found to be associated with depression.

Main Explanation

This patient meets the criteria for major depressive disorder (MDD), as indicated by his depressed mood, low energy, anhedonia, early-morning awakening, weight loss, and psychomotor depression. A major depressive episode is characterized by a period lasting at least two weeks with five or more of the following symptoms: depressed mood, anhedonia, insomnia or hypersomnia, change in appetite or weight, psychomotor retardation or agitation, low energy, poor concentration, thoughts of worthlessness or guilt, and recurrent thoughts of death or suicide; at least one of the symptoms must be depressed mood or anhedonia. Neuroendocrine studies in patients with MDD have demonstrated multiple clinical and subclinical alterations of normal human physiology including:

• Decreased neural transmission of monoamines (serotonin, norepinephrine, and dopamine), which can be recalled via the mnemonic “SuNDays are depressing.” 

• HPA-axis overactivity, resulting in subclinical hypercortisolemia with various neurotoxic effects, including volume loss in the frontal lobe and hippocampus. 

• Alterations in sleep architecture, most notably decreased rapid eye movement (REM) sleep latency and slow-wave sleep. 

P.S. If you or someone you know needs this, here's the number for the National Suicide Prevention Lifeline 1-800-273-8255 or text HOME to the Crisis Text Line at 741741. 

Major Takeaway

Neuroendocrine studies in patients with MDD have demonstrated both clinical and subclinical alterations in normal physiology, including decreased neural transmission of monoamines (serotonin, norepinephrine, and dopamine), hypercortisolemia, and changes in sleep architecture.

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596  

Keller, J., Gomez, R., Williams, G. et al. HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition. Mol Psychiatry 22, 527–536 (2017). https://doi.org/10.1038/mp.2016.120

Bremner, J. D., Narayan, M., Anderson, E. R., Staib, L. H., Miller, H. L., & Charney, D. S. (2000). Hippocampal Volume Reduction in Major Depression. American Journal of Psychiatry, 157(1), 115–118. doi:10.1176/ajp.157.1.115

Sharpley CF, Bitsika V, McMillan ME, Jesulola E, Agnew LL. The association between cortisol:C-reactive protein ratio and depressive fatigue is a function of CRP rather than cortisol. Neuropsychiatr Dis Treat. 2019;15:2467-2475. Published 2019 Aug 27. doi:10.2147/NDT.S213839