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A Longitudinal Magnetic Resonance Imaging Study

Daniel H. Mathalon, PhD, MD; Edith V. Sullivan, PhD; Kelvin O. Lim, MD; Adolf Pfefferbaum, MD

Arch Gen Psychiatry. 2001;58:148-157.

Background  We sought to determine whether the brain dysmorphology previously observed cross-sectionally in people with schizophrenia progresses over time and whether such progression is related to the severity of the illness course.

Subjects and Methods  Men with chronic schizophrenia (n = 24) and control men (n = 25) received 2 brain magnetic resonance imaging scans, on average 4 years apart. Changes in brain volume were adjusted for head-repositioning error and expressed as slopes (cubic centimeters per year). Clinical course severity for the schizophrenic patients was assessed using the mean of time 1 and time 2 Brief Psychiatric Rating Scale (BPRS) scores and the percentage of time the patient was hospitalized during the interscan interval.

Results  Schizophrenic patients exhibited faster volume decline than control subjects in right frontal gray matter and bilateral posterior superior temporal gray matter, as well as faster cerebrospinal fluid volume expansion in right frontal sulci, left lateral ventricle, and bilateral prefrontal and posterior superior temporal sulci. Faster rates of frontal sulcal expansion were related to greater BPRS total and positive symptom scores and longer time hospitalized. Prefrontal gray matter decline and sulcal expansion were associated with greater BPRS negative symptom scores and longer time hospitalized. Temporal lobe gray matter decline was associated with greater BPRS total and negative symptom scores.

Conclusions  This controlled study revealed that patients with chronic schizophrenia exhibited accelerated frontotemporal cortical gray matter decline and cortical sulcal and lateral ventricular expansion. Further, greater clinical severity was associated with faster rates of frontotemporal brain volume changes. These observations are consistent with a progressive pathophysiological process but need to be replicated in a larger sample.

From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif (Drs Mathalon, Sullivan, and Lim); the Psychiatry Service, VA Palo Alto Health Care System, Palo Alto, Calif (Dr Lim); and the Neuropsychiatry Program, Center for Health Sciences, SRI International, Menlo Park, Calif (Dr Pfefferbaum).

Corresponding author and reprints: Daniel H. Mathalon, PhD, MD, VA Connecticut Healthcare System, Psychiatry Service 116A, 950 Campbell Ave, West Haven, CT 06516 (e-mail: daniel.mathalon{at}yale.edu).

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