To the Editor Regarding an original investigation by Zaremba et al1 and accompanying editorial by Phillips2 recently published in JAMA Psychiatry, I fully appreciate the mounting interest in neural markers to identify the future course and relapse in patients with major depressive disorder (MDD). Undoubtedly, robust neuroanatomical correlates to patients’ individual trajectories will help advance breakthroughs in personalized treatments and research. However, I call for a certain degree of prudence, or even a reservation, based on the cognitive reserve hypothesis.3