Rotations 2.0 Episode 74 Generalized Anxiety Disorder

Episode 74 Generalized Anxiety Disorder

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Intro Music: KI Instrumental (Rock Celtic) by Lyrium-2025

Outro Music: Blues Rock by Alex Grohl

Courtesy of Pixabay under Creative Commons non-commercial use.

 Produced by: Todd Fredricks DO MSS 

Edited by: Todd Fredricks DO MSS

 Answers for Episode 73 Depression

Question 1 

A 34‑year‑old woman with major depressive disorder has persistent depressed mood, anhedonia, poor sleep, and impaired concentration. She completed two antidepressant trials (an SSRI followed by an SNRI), each at adequate dose and duration, with good adherence, but reports minimal improvement. She asks what this means and what options exist beyond “just trying another similar medication.”Which of the following is the best next step and most accurate characterization?

C. Identify treatment‑resistant depression (TRD) and discuss/referral for non‑monoaminergic options such as rTMS, ECT, or ketamine/esketamine.

Question 2 

 A neuroscience team uses a chronic unpredictable mild stress (CUMS) rodent model to study antidepressant mechanisms of repetitive transcranial magnetic stimulation (rTMS). They compare 5 Hz stimulation with 1 Hz stimulation and measure hippocampal endocannabinoid signaling. Which finding most strongly supports that rTMS’s antidepressant‑like effects are mediated through enhanced endocannabinoid signaling via CB1?

C. 5 Hz (high‑frequency) rTMS improves depressive‑like behavior, normalizes synaptic DAGLα and CB1 expression, increases hippocampal 2‑AG, and these effects are blocked by CB1 antagonists or by DAGLα/CB1 knockdown. 

Question 3 

A 56‑year‑old man with TRD begins electroconvulsive therapy (ECT) and reports significant mood improvement but develops new memory impairment. He asks if there is any known strategy to reduce cognitive side effects without eliminating benefit. You recall a preclinical depression model discussed in a review where a mechanistic intervention mitigated ECT‑associated memory problems while preserving antidepressant‑like effects. Which of the following best matches the findings summarized in the review?

C. Pharmacologically block CB1 receptors to reduce ECT‑induced memory deficits while maintaining antidepressant‑like efficacy.

Paper for Next Week:

Singh, Balwinder, Holly A. Swartz, Alfredo B. Cuellar-Barboza, Ayal Schaffer, Tadafumi Kato, Annemieke Dols, Sarah H. Sperry, Andrea B. Vassilev, Katherine E. Burdick, and Mark A. Frye. “Bipolar Disorder.” The Lancet 406, no. 10506 (August 30, 2025): 963–978. https://doi.org/10.1016/S0140-6736(25)01140-7.

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