Schizophrenia Research. 6 (1992) 55-65 Q 1992 Elsevier Science Publishers B.V. All rights reserved 0920.9964/92/$05.00 55 SCHIZO 00196 Neuropsychological probes of fronto-limbic system dysfunction in schizophrenia Olfactory identification and Wisconsin Card Sorting Performance Larry J. Seidman 1,2-4,5, Nancy L. Talbot’,6, Anthony G. Kalinowski’,7, Robert W. McCarley 3,4 Stephen V. Faraone , 2,4, William S. Kremen234, John R. Pepplezt4 Ming T. Tsuang2*4 1 Neuropsycho1og.v Laboratory, Clinical Psychology Service. Department of P.sj,chiatrl, ‘Section qf Psychiatric Epidemiology and Genetics. ‘LahoratorJ of Neuroscience. Department of Psychiatry, Massachusetts Mental Health Center, Harvard Medical School, Boston, MA, U.S.A., 4P.yychiatry Service, Brockion,l West Ro.uhury VA Medical Center, Brockion, MA, U.S.A., ‘Department of Psychiatry, Boston University School zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Medicine, Boston, MA, U.S.A.. ‘Department of Psychiatry, Strong Memorial Hospital, University of Rochester Medical School, Rochester, NY. U.S.A.. and 7Department of Psychology, Clark Universit!, Worcester, MA. U.S.A. (Received 3 I December 1990, revised received 28 May 199 1, accepted 3 I May 1991) Schizophrenic patients and normal control subjects took the University of Pennsylvania Smell Identification Test (UPSIT) and Wisconsin Card Sorting Test (WCST) as dual neuropsychological ‘probes’ of orbitofron- tal (OF) and dorsolateral (DL) prefrontal function respectively. Patients were significantly impaired on both tasks compared to controls. UPSIT and WCST performance were uncorrelated in patients but were positively correlated in controls. The lack of correlation found in the patients suggests that the tasks may be tapping independent dysfunctions in schizophrenia reflecting differential impairment in fronto-limbic brain systems. Individual profiles of preserved and impaired performance on the UPSIT and WCST suggested that three schizophrenic patients had OF dysfunction, five had DL dysfunction and seven had a generalized (OF and DL) frontal system dysfunction. The reduced ability of schizophrenic patients to identify odors was largely independent of many deficits or confounds typically associated with schizophrenia and did not appear to be simply a function of generalized deficit. These data are preliminary and require replication with larger samples and validation with other measures of fronto-limbic system dysfunction. K~JJ words: Fronto-limbic system; Olfactory identification; Wisconsin Card Sorting test; (Schizophrenia) INTRODUCTION The aim of the present study is to confirm previous findings of olfactory impairments in schizophrenia and to assess their relationship to cognitive deficits associated with frontal lobe dysfunctions. Several investigations have demonstrated that schizophre- nia is accompanied by a reduced ability to identify Correspondence to: L.J. Seidman, Psychology Service (R511A), Massachusetts Mental Health Center, 74 Fenwood Road, Boston, MA 02115, U.S.A. odors, as measured by the University of Pennsylva- nia Smell Identification Test (UPSIT) (Doty et al., 1984; Hurwitz et al., 1988; Kopala et al., 1989; Hurwitz and Clark, 1990). These studies have indicated that the impairment is unrelated to neuroleptic use, overt psychopathology, and smok- ing, and is more common among male than female subjects. The deficit has been described as an olfactory ugnosiu because the identification impair- ment is present without acuity deficit in schizophre- nia (Kopala and Clark, 1990). The odor identification deficit is not unique to