Schizophrenia in a Patient With Spinocerebellar Ataxia 2: Coincidence of Two Disorders or a Neurodegenerative Disease Presenting With Psychosis?

SCA2 is an autosomal dominant neurodegenerative disease caused by a pathological expansion of a CAG repeat sequence on chromosome 12q24 (MIM 183090). It is believed that the resultant mutated ataxin2 protein gains a toxic function leading to neuronal cell death and neurodegeneration (2), primarily in the cerebellum, brainstem, and spinal cord but also affecting the basal ganglia and cerebral cortex (3) . Typically, SCA2 develops in adulthood with slowed saccadic eye movements, peripheral neuropathy, decreased tendon reflexes, parkinsonism, myoclonus, and dementia. While most of the 28 types of autosomal dominant SCA reported to date involve some degree of neuropsychological deficit (4 – 6), including depression and personality change (7), psychosis appears to be less common. There is some evidence that SCA17 may appear with psychosis with or without chorea (8) ; however, to our knowledge, there are no cases of SCA2 in which psychosis was either the presenting symptom or a development during the course of the disease. A possible association exists between trinucleotide repeat expansions of the gene believed to cause SCA8 and susceptibility to major psychosis (9, 10) ; however, no such association has been reported for the repeat expansion that causes SCA2. In this case, we must ask whether SCA2 can account for the full spectrum of psychiatric, cognitive, and neurological symptoms or whether the concomitant diagnosis of schizophrenia is warranted.

Neurodegenerative disorders primarily affecting the striatum, such as Huntington’s disease and chorea-acanthocytosis, may present initially as movement disorders and/or psychiatric disturbances (11, 12) . When psychiatric symptoms develop in cerebellar disorders, they are often associated with neurological symptoms suggestive of striatal involvement (13) . This association suggests the possibility that psychosis in cerebellar disorders may be due to striatal involvement rather than to cerebellar pathology.

Alternatively, cerebellar dysfunction may account for psychiatric disease. In addition to the disorders of motor coordination and eye movements classically associated with cerebellar dysfunction, cerebellar abnormalities have been implicated in psychiatric disorders, including psychosis (14, 15) . It may be hypothesized that the co-occurrence of motor and psychiatric impairment in this case reflects the relative involvement of motor and cognitive domains that are known to be mediated by the frontal lobes and subserved by parallel circuits synaptically linking the frontal cortex, striatum, and thalamus (16) . Each of these frontostriatal circuits receives modulatory input from the cerebellum (17) . Within the cerebellum, the various functional domains, e.g., motor, vestibular, limbic, and cognitive, are topographically segregated (15) and form parallel interfaces with the frontostriatal circuits (17) . The diffuse atrophy of the cerebellum that our patient exhibited could conceivably contribute to dysfunction across multiple domains.

The etiology of our patient’s dementia is unclear because his neuropsychological deficits are consistent both with the type of subcortical dementia seen in a subset of schizophrenic patients (18) and with that seen in SCA2 (19, 20) . Although the precise chronology of the patient’s cerebellar disease is difficult to determine, the apparent temporal co-occurrence of the marked cognitive decline with the appearance of the first cerebellar motor impairments suggests that SCA2 accounts for the dementia.

Arguing against the hypothesis that SCA2 is responsible for our patient’s psychiatric disease is the fact that his age at presentation was typical for schizophrenia. In contrast, in SCA2, a repeat size in the range of that of our patient is typically associated with a slightly older age of onset, i.e., mid-20s to mid-50s (21) . Moreover, the development of somatic delusions, paranoia, and auditory hallucinations that resulted in the diagnosis of schizophrenia in our patient predated the appearance of chorea and other neurological symptoms by 6 years. In retrospect, however, one must question whether the physical complaints present from age 21 and interpreted as somatic delusions were in fact psychotic elaboration of sensations due to the emergence of a neurodegenerative disorder.

It is not possible to determine the etiology of our patient’s psychiatric disease or its relationship, if any, to his molecular diagnosis of SCA2. However, this case illustrates the importance of considering the possibility of neurodegenerative disease in patients who present with psychiatric symptoms. In particular, clinicians should be quick to evaluate unexpected cognitive or neurological symptoms that may be interpreted mistakenly as psychiatric in origin or as side effects of neuroleptics and anticholinergic medications. Correct and prompt diagnosis is essential for appropriate management, assessment of prognosis, and genetic counseling.

Received Feb. 25, 2008; revision received April 27, 2008; accepted April 28, 2008 (doi: 10.1176/appi.ajp.2008.08020285). From the Department of Neurology and the Department of Psychiatry, James J. Peters Veterans Affairs Medical Center; the Department of Neurology and the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the Department of Psychiatry and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore. Address correspondence and reprint requests to Dr. Walker, Department of Neurology (127), James J. Peters Veterans Affairs Medical Center, 130 West Kingsbridge Rd., Bronx, NY 10468; [email protected] (e-mail).

Dr. Margolis is a consultant for AstraZeneca and receives research support from Amaron and Forest. Dr. Sano is a consultant/advisor for Aventis, Bayer, Forest, GlaxoSmithKline, Janssen, Martek, Medivation, Novartis, Pfizer, Bristol-Myers Squibb, Ortho McNeil, Takeda, Voyager, Esai, and Elan. The remaining authors report no competing interests.