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

Abstract

The literature on social cognition abilities in bipolar disorder (BD) is controversial about the occurrence of theory of mind (ToM) alterations. In addition to other cerebral structures, such as the frontal and limbic areas, the processing of socially relevant stimuli has also been attributed to the cerebellum, which has been demonstrated to be involved in the above-mentioned disorder. Nevertheless, the cerebellar contribution to ToM deficits in bipolar patients needs to be elucidated further. To this aim, two tests assessing different components of ToM were used to evaluate the ability to appreciate affective and mental states of others in 17 individuals with a diagnosis of BD type 1 (BD1) and 13 with BD type 2 (BD2), both in the euthymic phase, compared to healthy matched controls. Cerebellar gray matter (GM) volumes were extracted and compared between BD1 and controls and BD2 and controls by using voxel-based morphometry. The results showed that BD1 patients were compromised in the cognitive and advanced components of ToM, while the BD2 ToM profile resulted in a more widespread compromise, also involving affective and automatic components. Both overlapping and differing areas of cerebellar GM reduction were found. The two groups of patients presented a pattern of GM reduction in cerebellar portions that are known to be involved in the affective and social domains, such as the vermis and Crus I and Crus II. Interestingly, in both BD1 and BD2, positive correlations were detected between lower ToM scores and decreased volumes in the cerebellum. Overall, BD2 patients showed a more compromised ToM profile and greater cerebellar impairment than BD1 patients. The different patterns of structural abnormalities may account for the different ToM performances evidenced, thus leading to divergent profiles between BD1 and BD2.

The role of the cerebellum in sequencing and predicting social and non-social events in patients with bipolar disorder

“…Eighteen patients with BD [mean age/SD: 39/7.99; years of education/SD: 15.56/2.66; M/F: 6/12] were enrolled for this study. The present study involved BD individuals who were previously recruited for other studies from our group ( Lupo et al, 2021b ; Olivito et al, 2022a , b ). All patients were diagnosed with bipolar disorder by an expert clinical psychiatrist from the Department of Psychiatry, Policlinico Umberto I Hospital using the Italian version of the Structured Clinical Interview for DSM-5 – Clinician Version (SCID-5-CV) ( First et al, 2017 ).…”

“…For the present study, the sample size was calculated with a priori power analyses using G-power software and estimating the effect size from relevant data taken from a previous study ( Olivito et al, 2022b ). A total sample size of 42 individuals (18 BD patients and 24 HS) is required to obtain 95% power (alpha: 0.05) under the expectation of a large effect size (d = 1.09).…”

“…While diverse meta-analytic studies have currently proven the presence of structural changes in certain subcortical areas in BD, such as hippocampus, thalamus, and amygdala ( Rossi et al, 2013 ; Hibar et al, 2016 ; Ding and Hu, 2021 ), considerable inconsistency between studies still exists about cerebellar structural changes in BD ( Ding and Hu, 2021 ). However, the involvement of the cerebellum in this disorder is currently being investigated on the basis of clinical and scientific evidence suggesting its implication in the pathology ( Mills et al, 2005 ; Argyropoulos et al, 2021 ; Lupo et al, 2021b ; Olivito et al, 2022a , b ). For example, the overshoot and undershoot that characterize responses to external or internal stimuli following cerebellar alterations have been associated with the states of mania and depression typical of bipolar disorder ( Schmahmann et al, 2007 ).…”

“…In this regard, the interest in examining the neural and behavioral mechanisms underlying the phases of symptom remission in BD has grown. In BD patients in the euthymic phase, cognitive deficits, such as visuospatial and verbal difficulties, and affective and ToM impairments have been described, strongly impacting patients’ quality of life ( Martinez-Aran et al, 2007 ; Bora et al, 2009 ; Gogos et al, 2010 ; Osher et al, 2011 ; Samamé et al, 2015 ; de Siqueira Rotenberg et al, 2020 ; Olivito et al, 2022b ). Furthermore, decreased volumes in the gray matter (GM) of cerebellar vermian and posterior areas have been documented ( Mills et al, 2005 ; Lupo et al, 2021b ) as well as disrupted functional and structural connectivity, which likely represents chronic impairments that persist during periods of symptom remission ( Argyropoulos et al, 2021 ; Olivito et al, 2022a ).…”

“…Furthermore, decreased volumes in the gray matter (GM) of cerebellar vermian and posterior areas have been documented ( Mills et al, 2005 ; Lupo et al, 2021b ) as well as disrupted functional and structural connectivity, which likely represents chronic impairments that persist during periods of symptom remission ( Argyropoulos et al, 2021 ; Olivito et al, 2022a ). In addition, a recent study revealed specific patterns of GM decrease in cerebellar vermis and Crus I and II both in patients with bipolar disorder type 1 and 2 in the euthymic phase, likely to explain the occurrence of ToM deficits ( Olivito et al, 2022b ). It must be noted that sequential abilities and prediction abilities related to social and non-social functions have never been investigated in BD.…”