Cerebellar-dependent eyeblink conditioning deficits in schizophrenia spectrum disorders

Accumulating evidence suggests that abnormalities in neural circuitry and timing associated with the cerebellum may play a role in the pathophysiology of schizophrenia. Schizotypal personality disorder (SPD) may be genetically linked to schizophrenia, but individuals with SPD are freer from potential research confounds and may therefore offer insight into psychophysiological correlates of schizophrenia. The present study employed a delay eyeblink conditioning (EBC) procedure to examine cerebellar-dependent learning in schizophrenia, SPD, and healthy control subjects (n = 18 per group) who were matched for age and gender. The conditioned stimulus was a 400-ms tone that coterminated with a 50 ms unconditioned stimulus air puff. Cognitive performance on the Picture Completion, Digit Symbol Coding, Similarities, and Digit Span subscales of the Wechsler Adult Intelligence Scale--Third Edition was also investigated. The schizophrenia and SPD groups demonstrated robust EBC impairment relative to the control subjects; they had significantly fewer conditioned responses (CRs), as well as smaller CR amplitudes. Schizophrenia subjects showed cognitive impairment across subscales compared with SPD and control subjects; SPD subjects showed intermediate performance to schizophrenia and control subjects and performed significantly worse than controls on Picture Completion. Impaired EBC was significantly related to decreased processing speed in schizophrenia spectrum subjects. These findings support the role of altered cortico-cerebellar-thalamic-cortical circuitry in the pathophysiology of schizophrenia spectrum disorders.