FORT MYERS, FLA— The function of the cerebellum has undergone significant reassessment during the past several years. Although the structure traditionally has been known for its role in movement and balance, increasing evidence points to involvement in cognition and emotion, as well. For example, recent studies indicate that patients with cerebellar damage show impairment in executive function, language, and other cognitive abilities; one neuroimaging study has demonstrated that the cerebellum is activated when transient sadness is induced in psychiatrically normal individuals (though other regions are also activated).

At the annual meeting of the American Neuropsychiatric Association, investigators from Johns Hopkins School of Medicine reported yet another intriguing finding: a remarkably high rate of psychopathology in patients with cerebellar degeneration. In a sample of 31 patients with spinocerebellar ataxia (SCA), multiple system atrophy (MSA), or other types of cerebellar degeneration, 78% had a diagnosable psychiatric disorder, and two thirds met criteria for a DSM-IV mood disorder. Moreover, the patients showed widespread impairment on a battery of neuropsychologic tests, with one in five having either dementia or a cognitive disorder.

These findings may surprise even neurologists and other clinicians who regularly treat this population, said Iracema Leroi, MD, an Assistant Professor of Psychiatry at Johns Hopkins. “The motor aspects of cerebellar disease are so prevalent, so obvious, that often the psychiatric and cognitive aspects get less attention.” In addition, she said, the findings provide further evidence that “we need to start including the contribution of the cerebellum in our understanding of cognition and emotion.”

A HETEROGENEOUS SAMPLE

In the study, 31 patients with cerebellar degeneration, 21 with Huntington’s disease (HD), and 29 matched controls underwent an extensive psychiatric, neurologic, cognitive, and functional assessment that included a structured psychiatric interview and eight measures of psychopathology. The cerebellar degeneration group included 15 subjects with familial SCA, four with sporadic SCA, five with MSA involving predominantly cerebellar degeneration, and seven with cerebellar degeneration that did not meet criteria for SCA or MSA. Disease duration was at least five years (mean, 12) for both the cerebellar and HD patients, and all three groups had a mean age of about 52.

Perhaps the most remarkable finding from these detailed evaluations was that 21 of the cerebellar degeneration patients (68%) met criteria for a mood disorder, including 11 (35%) with major depression and 10 (32%) with either dysthymia or a brief depressive episode. In contrast, only 43% of HD patients and 31% of controls had a mood disorder. The fact that affective changes were more common in cerebellar patients than in the HD group is “striking,” said Dr. Leroi, “because Huntington’s disease patients are generally recognized as a very psychiatrically vulnerable group—particularly with regard to mood—and have very high suicide rates. Yet this hasn’t been recognized with cerebellar patients.”

Personality changes were also far more common in patients with cerebellar degeneration (26%) than in controls (0%), though more common still in HD patients (48%). Rates of anxiety (13%) and psychotic disorders (10%) were higher in cerebellar patients than in controls as well, though neither difference was statistically significant. Overall, 78% of cerebellar degeneration patients and 81% of HD patients had one or more psychiatric disorders, compared to only 41% of those in the control group.

Could the increased rate of depression in cerebellar patients be due to a reactive phenomenon? Not entirely, the investigators believe. For one thing, although the rate of depressive disorders among caregivers of cerebellar patients (40%) was higher than the norm, it fell far short of the rate for the patients themselves, suggesting that stress alone does not account for the mood problems. Moreover, several studies have found evidence of cerebellar involvement in depression, including one report of cerebellar atrophy in depressed bipolar patients. Finally, from a neuroanatomic standpoint, the cerebellum is not only connected to the dorsolateral prefrontal cortex, the anterior cingulate, and other regions involved in behavior and cognition, but it receives noradrenergic, serotonergic, and dopaminergic inputs from the brainstem nuclei, suggesting mechanisms by which cerebellar changes might influence psychiatric and cognitive function.

IMPAIRED COGNITION

The clinical picture for cerebellar degeneration patients was also grim with respect to cognitive function. “Across all aspects of the battery of cognitive and psychomotor tasks, the cerebellar patients performed worse than controls,” Dr. Leroi reported. Although the deficits were sometimes severe—three patients (10%) actually had full-fledged dementia—in a clinical setting these cognitive problems are largely overshadowed by the neurologic aspects of the disease. “Often patients have already stopped working and are on disability because of the motor problems, so they are not in situations where the cognitive deficits would be very obvious,” Dr. Leroi observed.

The high prevalence of cognitive impairment among patients with HD is a well-known phenomenon, of course, and the current study bears this out. Not only did HD patients perform even worse than cerebellar patients did on most neuropsychologic tests, but 71% had dementia or a cognitive disorder, compared with 19% of patients with cerebellar disease.

Functional impairment was similar and substantial in both disease groups. As one might expect, a patient’s degree of motor disability was a major predictor of functional impairment, although scores on the apathy scale of the Neuropsychiatric Inventory also correlated highly with daily functioning.

“PURE” CEREBELLAR DISEASE?

Most patients with SCA or MSA also have some degree of abnormality in noncerebellar brain regions. Thus, Dr. Leroi suggested that it would be particularly interesting to focus attention on patients with SCA type 6, whose neuroanatomic defects are almost exclusively confined to the cerebellum. “If you’re trying to define the relative contribution of the cerebellum to the cognitive and psychiatric aspects of the disease, it’s nice to have a pure cerebellum group.” Unfortunately, only two patients in the current study had the SCA6 genotype, precluding any useful analysis.

However, the Johns Hopkins group does have plans for several studies that may further elucidate the role of the cerebellum in cognition and emotion. One is a comparison between cerebellar degeneration patients and persons with a similarly disabling non-neurodegenerative chronic disease; this would help sort out the relative role of cerebellar physiology and psychosocial factors in the etiology of depressive disorders. Unfortunately, finding an ideal control group has proven somewhat elusive; persons with spinal cord injuries, for example, would be appropriate in many respects but tend to be much younger. The researchers are currently considering using rheumatoid arthritis patients as a comparison group. They also plan to enlarge their sample of cerebellar patients and follow them longitudinally.

In the meantime, Dr. Leroi noted, the realization that psychopathology is so prevalent in cerebellar degeneration has important implications for the 150,000 patients with the disease. “At this point, we can’t treat the motor aspects at all,” she said. “But if we can treat the depression and enhance people’s quality of life and overall ability to function, that’s significant.”

Dr. Leroi’s coauthors included Russell L. Margolis, MD, Elizabeth O’Hearn, MD, Jason Brandt, PhD, Constantine Lyketsos, MD, MHS, and Christopher Ross, MD, PhD, all of Johns Hopkins School of Medicine.

—Peter Doskoch

Suggested Reading
Rapoport M, van Reekum R, Mayberg H. The role of the cerebellum in cognition and behavior: a selective review. J Neuropsychiatry Clin Neurosci. 2000;12:193-198.

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