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Relationship of Neuroanatomical Changes to Clinical and Neurobehavioral Measures

Raquel E. Gur, MD, PhD; Patricia Cowell, PhD; Bruce I. Turetsky, MD; Fiona Gallacher, MS; Tyrone Cannon, PhD; Warren Bilker, PhD; Ruben C. Gur, PhD

Arch Gen Psychiatry. 1998;55:145-152.

Background  Cross-sectional neuroanatomical studies have reported abnormalities in schizophrenia that relate to disease variables. Longitudinal neuroimaging investigations that integrate anatomical, clinical, and neurobehavioral measures may help clarify the pathogenesis of schizophrenia.

Methods  Magnetic resonance brain imaging and neurobehavioral studies were conducted at baseline and after 30.63±12.92 months (mean±SD) in 40 patients with schizophrenia (23 men and 17 women) and 17 healthy controls (13 men and 4 women). The schizophrenia group included 20 first-episode and 20 previously treated subjects. Volumes of whole-brain, cerebrospinal fluid, and frontal and temporal lobes were measured. The severity of negative and positive symptoms was assessed, medications were monitored, and neurobehavioral functioning in 8 domains was evaluated.

Results  Both first-episode and previously treated patients had smaller brains and frontal and temporal lobes than controls at intake. Longitudinally, reduction in frontal lobe volume was found only in patients, whereas temporal lobe reduction was also seen in controls. The association between volume reduction and symptom changes differed between patient groups, but volume reduction was associated with decline in some neurobehavioral functions in both groups. Exploratory analysis suggested that neuroleptic dose is correlated with changes in all 3 domains.

Conclusions  The existence of neuroanatomical and neurobehavioral abnormalities in patients with first-episode schizophrenia indicates that the brain dysfunction occurred before clinical presentation. However, there is also evidence of progression, in which anatomical changes may affect some clinical and neurobehavioral features of the illness in some patients.

From the Mental Health Clinical Research Center, Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia.

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