Impaired Cerebellar-Dependent Eyeblink Conditioning in First-Degree Relatives of Individuals With Schizophrenia

Consistent with reports of cerebellar structural, functional, and neurochemical anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is also present in schizotypal personality disorder, an intermediate p...

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Bibliographic Details
Published in:Schizophrenia bulletin 2014-09, Vol.40 (5), p.1001-1010
Main Authors: BOLBECKER, Amanda R, KENT, Jerillyn S, PETERSEN, Isaac T, KLAUNIG, Mallory J, FORSYTH, Jennifer K, HOWELL, Josselyn M, WESTFALL, Daniel R, O'DONNELL, Brian F, HETRICK, William P
Format: Article
Language:English
Subjects:
Adult
Adult and adolescent clinical studies
Association Learning - physiology
Biological and medical sciences
Blinking - physiology
Cerebellum - physiopathology
Conditioning, Eyelid - physiology
Electromyography
Female
Humans
Male
Medical sciences
Middle Aged
Nuclear Family
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Psychotic Disorders - genetics
Psychotic Disorders - physiopathology
Regular
Schizophrenia
Schizophrenia - genetics
Schizophrenia - physiopathology
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Summary:Consistent with reports of cerebellar structural, functional, and neurochemical anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is also present in schizotypal personality disorder, an intermediate phenotype of schizophrenia. The present work sought to determine whether dEBC deficits exist in nonpsychotic first-degree relatives of individuals with schizophrenia. A single-cue tone dEBC paradigm consisting of 10 blocks with 10 trials each (9 paired and 1 unpaired trials) was used to examine the functional integrity of cerebellar circuitry in schizophrenia participants, individuals with a first-degree relative diagnosed with schizophrenia, and healthy controls with no first-degree relatives diagnosed with schizophrenia. The conditioned stimulus (a 400ms tone) coterminated with the unconditioned stimulus (a 50ms air puff to the left eye) on paired trials. One relative and 2 healthy controls were removed from further analysis due to declining conditioned response rates, leaving 18 schizophrenia participants, 17 first-degree relatives, and 16 healthy controls. Electromyographic data were subsequently analyzed using growth curve models in hierarchical linear regression. Acquisition of dEBC conditioned responses was significantly impaired in schizophrenia and first-degree relative groups compared with controls. This finding that cerebellar-mediated associative learning deficits are present in first-degree relatives of individuals with schizophrenia provides evidence that dEBC abnormalities in schizophrenia may not be due to medication or course of illness effects. Instead, the present results are consistent with models of schizophrenia positing cerebellar-cortical circuit abnormalities and suggest that cerebellar abnormalities represent a risk marker for the disorder.
ISSN:0586-7614
1745-1701
DOI:10.1093/schbul/sbt112