Brain Morphology, Dopamine, and Eye-Tracking Abnormalities in First-Episode SchizophreniaPrevalence and Clinical Correlates
Jeffrey A. Lieberman, MD;
Darlene Jody, MD;
Jose Ma. J. Alvir, DrPH;
Manzar Ashtari, PhD, GD;
Deborah L. Levy, PhD;
Bernhard Bogerts, MD;
Gustav Degreef, MD;
David I. Mayerhoff, MD;
Thomas Cooper, MA
Arch Gen Psychiatry. 1993;50(5):357-368.
Abstract
Objective
To characterize the pathophysiology of schizophrenia and to identify biologic markers in first-episode patients with no or little prior treatment exposure.
Design
Prospective study of an inception cohort.
Setting
Psychiatric division of an academic medical center with a suburban metropolitan catchment area.
Patients
70 patients in their first episode of schizophrenia (77%) or schizoaffective disorder (23%) with no (70%) or limited prior neuroleptic exposure (30%), and 50 healthy volunteer control subjects.
Assessment Measures
Demographic and clinical evaluations of natural history and psychopathology; methylphenidate hydrochloride and apomorphine hydrochloride stimulation tests as measures of central nervous system dopamine activity; brain magnetic resonance imaging; eyetracking examinations.
Results
Preliminary analyses demonstrate that pathobiologic features previously identified in heterogeneous and primarily chronically ill patients are also present in subgroups during their first episode. These incude psy- chotogenic response to methylphenidate (59%), abnormal growth hormone (GH) secretion (50%), abnormal brain morphology (31%), and eye-tracking dysfunction (51%). An association of pathobiologic variables with increased symptom severity and earlier age of onset was observed but not statistically significant. The strongest associations among biologic variables were for the following: GH secretion and psychotogenic response to methylphenidate, which may reflect increased dopamine agonist neural activity; decreased GH response to apomorphine and thirdventricle enlargement, which may represent a neuropathologic correlate of anterior pituitary abnormalities; and morphologic abnormalities of the medial temporal lobe and third ventricle were associated with normal eye tracking, suggesting that these pathobiologic features are mediated by distinct processes.
Conclusions
These phenomena appear to be a consequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. It remains to be determined if these biologic phenomena will remain stable over time or change with disease progression. A companion article examines the clinical significance of these findings.
Author Affiliations
From the Department of Psychiatry, Hillside Hospital, Glen Oaks, NY.
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