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Recently, Weinberger and McClure¹ offered a provocative and cautionary perspective in connection with mounting longitudinal neuroimaging evidence of progressive brain volume decline in schizophrenia. Unfortunately, they confuse this increasingly well-documented phenomenon with a neurodegenerative hypothesis of schizophrenia. We agree with the authors that neurodegenerative processes involving inflammation and neuronal loss are unlikely based on the neuropathology literature, and that volumetric magnetic resonance imaging (MRI) data cannot elucidate the cellular or molecular mechanisms underlying progressive volume loss. This does not diminish the importance of longitudinal neuroimaging studies, whose rationale is to examine whether brain dysmorphology is static or progressive. This rationale is as valid today as it was in 1988² and 1994,³ when Dr Weinberger's group reported nonprogressive ventricular enlargement in schizophrenia and cited these findings as evidence that schizophrenia is a static neurodevelopmental encephalopathy.⁴ In contrast with these early studies, most of which used computed tomography, recent positive studies are . . . [Full Text of this Article]

Daniel H. Mathalon, PhD, MD
Department of Psychiatry
Yale University School of Medicine
Psychiatry Service 116A
Veterans Affairs Connecticut Healthcare System
950 Campbell Ave
West Haven, CT 06516
(e-mail: daniel.mathalon@yale.edu)

Judith L. Rapoport, MD
Bethesda, Md

Kenneth L. Davis, MD
New York, NY

John H. Krystal, MD
New Haven, Conn

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