Comparison of Cerebellar Grey Matter Alterations in Bipolar and Cerebellar Patients: Evidence from Voxel-Based Analysis

Abstract

The aim of this study was to compare the patterns of cerebellar alterations associated with bipolar disease with those induced by the presence of cerebellar neurodegenerative pathologies to clarify the potential cerebellar contribution to bipolar affective disturbance. Twenty-nine patients affected by bipolar disorder, 32 subjects affected by cerebellar neurodegenerative pathologies, and 37 age-matched healthy subjects underwent a 3T MRI protocol. A voxel-based morphometry analysis was used to show similarities and differences in cerebellar grey matter (GM) loss between the groups. We found a pattern of GM cerebellar alterations in both bipolar and cerebellar groups that involved the anterior and posterior cerebellar regions (p = 0.05). The direct comparison between bipolar and cerebellar patients demonstrated a significant difference in GM loss in cerebellar neurodegenerative patients in the bilateral anterior and posterior motor cerebellar regions, such as lobules I−IV, V, VI, VIIIa, VIIIb, IX, VIIb and vermis VI, while a pattern of overlapping GM loss was evident in right lobule V, right crus I and bilateral crus II. Our findings showed, for the first time, common and different alteration patterns of specific cerebellar lobules in bipolar and neurodegenerative cerebellar patients, which allowed us to hypothesize a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder.

Theory of mind profile and cerebellar alterations in remitted bipolar disorder 1 and 2: a comparison study

“…Among the behavioral alterations most commonly reported in these patients, changes in the emotional sphere are described, such as greater irritability, impulsivity, anxiety, dysphoria, emotional lability, difficulty in recognizing emotions, and attributing mental states of others, components that fall into the SC domain (Schmahmann and Sherman, 1998 ; Lupo et al, 2018a , b ; Clausi et al, 2019b ). On the other hand, several clinical studies have highlighted the presence of structural alterations of the cerebellum in subjects affected by various psychopathologies, such as schizophrenia (Okugawa et al, 2007 ), major depressive disorder (Bora and Berk, 2016 ), and bipolar disorder (Sani et al, 2016 ; Lupo et al, 2021 ), leading to the hypothesis that the cerebellum may be involved in the genesis of some typical symptoms of these disorders. Different studies aimed at analyzing the anatomical substrate of BD have found a significant pattern of atrophy involving cerebellar regions, such as the cerebellar vermis, the anterior lobule V and posterior lobules Crus I and Crus II (Mills et al, 2005 ; Lupo et al, 2021 ), which are known to be strictly connected to frontal, temporal, and limbic social brain regions.…”

Aberrant Cerebello-Cerebral Connectivity in Remitted Bipolar Patients 1 and 2: New Insight into Understanding the Cerebellar Role in Mania and Hypomania

“…As reported in the cerebellar cognitive-affective syndrome (CCAS) [ 9 ], cerebellar alterations have been related to mood disturbances following both pure cerebellar lesion and neurodegenerative cerebellar pathologies [ 14 , 39 ]. Cerebellar structural alterations have been extensively reported in BD [ 3 , 16 , 40 ]. From an anatomical point of view, this is supported by the close cerebellar connections with the prefrontal-striatal-circuits and limbic structures, i.e., the amygdala and the hippocampus [ 41 ].…”

“…Although the abnormal FC in BD patients has been consistently reported during acute mood episodes [18], a persistent FC vulnerability has been hypothesized also during euthymia when bipolar patients exhibit minimal symptoms by definition [19]. This is probably the result of over-reactive emotional brain networks (i.e., anterior limbic network) that would always leave patients at risk for mood and cognitive disturbances [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…Cerebellar structural alterations have been reported in earlier and later stages of BD [ 3 ] with no difference between BD1 and BD2 subtypes. Common and different alteration patterns of specific cerebellar lobules have been reported in a recent voxel-based morphometry study (VBM) [ 16 ] comparing mixed bipolar and neurodegenerative cerebellar patients, suggesting a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder.…”

The Role of the Posterior Cerebellum in Dysfunctional Social Sequencing

“…More importantly, we further suggest that the posterior cerebellum may play a central role in social dysfunctions observed in many clinical pathologies. Indeed, deficits in mentalizing at large, and in the posterior cerebellum in particular, may play a crucial role in the onset and maintenance of psychiatric disorders related to limited mentalizing and emotion recognition, such as autism spectrum disorder [12][13][14], depression [15,16], bipolar disorder [17], obsessive compulsive disorder [18][19][20][21], addiction [22][23][24][25], and schizophrenia [26][27][28][29][30].…”