Cerebellar–Subcortical Circuits and Mania in Cerebellar Disease

SIR: Recently Rapoport and colleagues¹ selectively reviewed the role of the cerebellum in cognition and behavior. Although cerebellar relationships with the cerebral cortex via the thalamus were cited, I wish to add to the discussion by calling attention to cerebellar connections to subcortical structures of significance in neuropsychiatric disorders.

Whereas the hippocampus and fornix project to the cerebellum, the cerebellum projects to the septum, amygdala, hippocampus, locus ceruleus, ventral tegmental area, substantia nigra, striatum, globus pallidus, pedunculopontine nucleus, and thalamus (including mediodorsal, intralaminar, and pulvinar nuclei).² Thus, the cerebellum may exert influence over critical subcortical pathways in neuropsychiatry, including limbic circuits, hippocampus, and temporal lobe connections, monoamine projections, and basal ganglia–thalamocortical circuits influencing temporal and prefrontal cortex.

Furthermore, these connections appear to have functional significance. Cerebellolimbic discharges are observed in primate manic-like aggression (Harlow and Harlow 1962;² Dow et al. 1974²), human mood has been influenced by cerebellar stimulation (Cooper et al. 1974²), cerebellar lesions affect contralateral basal ganglia and bilateral frontal blood flow (Rousseaux and Steinling 1992²), and dentatothalamoprefrontal circuits are thought to mediate the frontal readiness potential (Shibasaki et al. 1978²). The potential importance of cerebellar connections with these subcortical structures is therefore worth further consideration.

Although study of the cerebellum in primary bipolar disorders has not as yet led to clear findings, the study of secondary bipolar disorders after isolated lesions may provide supplemental evidence for cerebellar relevance in mood disorders. We have described 3 bipolar cases associated with cerebellar hypoplasia, cerebellar atrophy (associated with rapid-cycling bipolar disorder), and a dentatorubrothalamic tract lesion (associated with mixed-type bipolar disorder) among 15 patients screened for isolated cerebellar lesions. This 20% rate was significantly greater than normative population rates (P<0.005) and rates in control subjects with isolated focal subcortical cerebral hemispheric lesions (P<0.05), perhaps suggesting an important effect of cerebellar lesions in relation to mania. Moreover, there have been a number of other reports describing manic features in the context of cerebellar pathology (Cutting 1976;² Hamilton et al. 1983;² Yadalam et al. 1985;² Endo 1986²). Kalayam et al.³ have reported 3 cases of SCID-diagnosed DSM-III-R mania associated with acoustic neuromas. The cerebellum was retracted and manipulated in 2 of these cases, and the other case was associated with cerebellar atrophy.

Taken together, these findings provide additional preliminary evidence of association between cerebellar lesions and the development of mania. It is possible that cerebellosubcortical circuits are involved in mediating mood disturbances.