A 55-year-old woman with chronic stable angina presents with fatigue, difficulty concentrating, and depressed mood that began 2 weeks after her cardiologist started metoprolol succinate 100 mg daily for rate control. She denies suicidal ideation, prior psychiatric history, recent stressors, or substance use. Vital signs show HR 52 bpm, BP 110/70 mmHg, RR 14/min, SpO2 98% on room air. Physical examination is unremarkable with no thyroid enlargement. Labs show TSH 2.1 mIU/L (normal), B12 340 pg/mL (low-normal), CBC normal, and BMP unremarkable. Which of the following best explains the temporal relationship between her medication initiation and symptom onset?

1. A)Lipophilic beta-blockers penetrate the blood-brain barrier and reduce central noradrenergic activity, which is necessary for mood and cognitionGABARITO
2. B)Metoprolol inhibits hepatic metabolism of concurrent medications, leading to toxic accumulation
3. C)Beta-blockade reduces cerebral blood flow below the autoregulatory threshold, causing diffuse CNS hypoperfusion
4. D)Metoprolol-induced bradycardia causes hyperkalemia, which depolarizes neuronal membranes and impairs synaptic transmission
5. E)The medication depletes central serotonin stores by competitive inhibition of monoamine reuptake