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

Introduction: Advances in the operational mode of the cerebellum indicate a role in sequencing and predicting non-social and social events, crucial for individuals to optimize high-order functions, such as Theory of Mind (ToM). ToM deficits have been described in patients with remitted bipolar disorders (BD). The literature on BD patients' pathophysiology reports cerebellar alterations; however, sequential abilities have never been investigated and no study has previously focused on prediction abilities, which are needed to properly interpret events and to adapt to changes. Methods: To address this gap, we compared the performance of BD patients in the euthymic phase with healthy controls using two tests that require predictive processing: a ToM test that require implicit sequential processing and a test that explicitly assesses sequential abilities in non-ToM functions. Additionally, patterns of cerebellar gray matter (GM) alterations were compared between BD patients and controls using voxel-based morphometry. Results: Impaired ToM and sequential skills were detected in BD patients, specifically when tasks required a greater predictive load. Behavioral performances might be consistent with patterns of GM reduction in cerebellar lobules Crus I-II, which are involved in advanced human functions. Discussion: These results highlight the importance of deepening the cerebellar role in sequential and prediction abilities in patients with BD.

The Cerebellum Gets Social: Evidence from an Exploratory Study of Cerebellar, Neurodevelopmental, and Psychiatric Disorders.

Social prediction is a key feature of social cognition (SC), a function in which the modulating role of the cerebellum is recognized. Accordingly, cerebellar alterations are reported in cerebellar pathologies, neurodevelopmental disorders, and psychiatric conditions that show SC deficits. Nevertheless, to date, no study has directly compared populations representative of these three conditions with respect to SC and cerebellar alterations. Therefore, the present exploratory study aimed to compare the SC profiles of individuals with cerebellar neurodegenerative disorders (CB), autism (ASD), bipolar disorder type 2 (BD2), or healthy subjects (HS) using a battery of social tests requiring different degrees of prediction processing. The patterns of cerebellar gray matter (GM) alterations were compared among the groups using voxel-based morphometry. Compared to HS, the clinical groups showed common SC deficits in tasks involving a moderate to high level of prediction. The behavioral results of the clinical groups are consistent with the presence of overlapping GM reduction in cerebellar right Crus II, an area notably involved in complex social processing and prediction. Although exploratory and preliminary, these results deepen the cerebellar role in social prediction and highlight the transdiagnostic value of the cerebellum in social functioning and prediction in pathologies of different aetiologies, forecasting novel possibilities for shared interventions.

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

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.

Differential diagnosis of borderline personality disorder and bipolar disorder: Self-concept, identity and self-esteem.

Symptoms of borderline personality disorder (BPD) and bipolar disorder (BD) often overlap. In some cases, it is difficult to conduct a differential diagnosis based only on current diagnostic criteria Therefore, it is important to find clinical factors with high discriminatory specificity that, used together with structured or semi-structured interviews, could help improve diagnostic practice. We propose that a clinical analysis of identity, self-concept and self-esteem may help distinguish the two disorders, when they are not co-morbid. Our review of the studies that analyse these constructs in BD and BPD, separately, points in the direction of qualitative differences between the two disorders. In BPD, there is a well-documented identity diffusion, and the self-concept appears predominantly negative; shifts in self-concept and self-esteem are often tied to interpersonal triggers. In BD, patients struggle with their identity, but narrative identity might be less compromised compared with BPD; the shifts in self-concept and self-esteem appear more linked to internal (i.e. mood and motivational) factors. We end the paper by discussing the implications for clinicians and ideas for future comparative research.

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

Bipolar disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD, 38.64/13.48; M/F, 9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD, 41.42/14.38; M/F, 6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD, 45.65/14.15; M/F, 15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia.

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

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.

Cross-sectional similarities and differences between schizophrenia, schizoaffective disorder and mania or mixed mania with mood-incongruent psychotic features.

BACKGROUND: The cross-sectional clinical differentiation of schizophrenia or schizoaffective disorder from mood-incongruent psychotic mania or mixed mania is difficult, since pathognomonic symptoms are lacking in these conditions. AIMS OF THE STUDY: To compare a series of clinical variables related to mood and cognition in patient groups with DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, mood-incongruent psychotic mania and mood-incongruent psychotic mixed mania. METHODS: One hundred and fifty-one consecutive patients were evaluated in the week prior to discharge by using the structured clinical interview for DSM-III-R-patient edition (SCID-P). Severity of psychopathology was assessed by the 18-item version of the brief psychiatric rating scale (BPRS) and negative symptoms by the scale for assessment of negative symptoms (SANS). Level of insight was assessed with the scale to assess unawareness of mental disorders (SUMD). RESULTS: There were no differences in rates of specific types of delusions and hallucinations between subjects with schizophrenia, schizoaffective disorder, psychotic mania and psychotic mixed mania. SANS factors scores were significantly higher in patients with schizophrenia than in the bipolar groups. Patients with mixed state scored significantly higher on depression and excitement compared to schizophrenia group and, to a lesser extent, to schizoaffective group. Subjects with schizophrenia showed highest scores on the SUMD indicating that they were much more compromised on the insight dimension than subjects with psychotic mania or mixed mania. CONCLUSION: Negative rather than affective symptomatology may be a useful construct to differentiate between schizophrenia or schizoaffective disorders from mood-incongruent psychotic mania or mixed mania.

Awareness of illness in patients with bipolar I disorder with or without comorbid anxiety disorders.

BACKGROUND: The present study examined whether specific types of comorbid anxiety disorders, namely panic disorder (PD), social phobia (SP) and obsessive-compulsive disorder (OCD) are differentially associated with course variables and insight into bipolar illness. METHOD: The sample consisted of 151 consecutively hospitalized patients with bipolar I disorder. They were assessed in the week prior to discharge using the Structured Clinical Interview for DSM-III-R (SCID-P), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale (GAF) and the Hopkins Symptom Checklist (HSCL-90). Level of insight was assessed with the Scale to assess Unawareness of Mental Disorders (SUMD). RESULTS: Of the 151 bipolar subjects, 92 had no PD, SP and OCD comorbidity, 35 had PD and 24 had SP and/or OCD. The three groups differed significantly on the current awareness of illness and treatment response scores and the retrospective awareness of illness and treatment response scores. Post-hoc analyses revealed that, compared with bipolar patients without PD/SD/OCD and those with comorbid PD, patients with comorbid SP and/or OCD had better insight on current awareness of illness, current awareness of treatment response, retrospective awareness of illness and retrospective awareness of treatment response. The regression analysis showed that the presence of no panic type anxiety comorbidity was a predictor of good insight. CONCLUSIONS: These data indicate the value of identifying comorbid anxiety disorders in patients with bipolar illness. The results could be interpreted as evidence of discrete disorders within the bipolar spectrum, one that is characterized by, among other things, SP and/or OCD with good insight, another characterized by PD with poor insight.

Insight into illness in patients with mania, mixed mania, bipolar depression and major depression with psychotic features.

BACKGROUND: Poor insight into illness is a common feature of bipolar disorder and one that is associated with poor clinical outcome. Empirical studies of illness awareness in this population are relatively scarce with the majority of studies being published over the previous decade. The study reported here sought to replicate previous report findings that bipolar patients frequently show high levels of poor insight into having an illness. We also wanted to examine whether group differences in insight exist among bipolar manic, mixed and unipolar depressed patients with psychotic features. METHODS: A cohort of 147 inpatients with DSM-III-R bipolar disorder and 30 with unipolar depression with psychotic features, were evaluated in the week prior to discharge using the Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P), the Brief Psychiatric Rating Scale (BPRS) and the Scale to assess Unawareness of Mental Disorder (SUMD). RESULTS: Insight into specific aspects of the illness was related to the polarity of mood episode: patients with mania showed significantly poorer insight compared with those with mixed mania, bipolar depression and unipolar depression. A linear regression analysis using SUMD score as the dependent variable and symptoms of mania as the independent variable found that specific manic symptoms did not account for level of insight. Similar results were obtained when the mean insight scores of patients with and without grandiosity were contrasted. CONCLUSIONS: We hypothesize that the lack of association between level of insight and total number of manic symptoms or with specific manic symptoms may be related to the persistence of subsyndromal symptoms in patients remitting from a manic episode.

Social anxiety spectrum: gender differences in Italian high school students.

Gender differences in the social anxiety spectrum and their correlation with other psychopathological features were analyzed in 520 students by using two questionnaires: the Social Anxiety Spectrum Self-Report (SHY-SR), which explores social anxiety spectrum, and the General Spectrum Measure (GSM), which explores panic-agoraphobia, mood, obsessive-compulsive, and eating-behavior features. Mean SHY-SR total score was significantly higher in women than in men, and gender differences were particularly pronounced for interpersonal sensitivity domain. Likewise, GSM scores were higher in women, except for the manic section. The SHY-SR domains correlated significantly with all GSM sections, except for the manic section. In conclusion, women reported more symptoms than men (who belonged to different psychopathologic dimensions) and displayed a profile of social anxiety spectrum that differs quantitatively but not qualitatively from the men's profile. The correlation between social anxiety spectrum and other psychopathological features mirrors previous findings concerning the high comorbidity of axis-I social anxiety disorder.

Measuring social anxiety and obsessive-compulsive spectra: comparison of interviews and self-report instruments.

The present report analyzes the agreement between the interview and the self-report formats of the instruments Structured Clinical Interview for Social Anxiety Spectrum (SCI-SHY) and Structured Clinical Interview for Obsessive Compulsive Spectrum (SCI-OBS), already validated, in three psychiatric patient samples and controls. Thirty patients (10 with obsessive-compulsive disorder [OCD], 10 with social anxiety disorder [SAD], 10 with recurrent unipolar depression in remission) and 20 control subjects (10 university students, 10 ophthalmologic patients) were assessed using the SCI-SHY, the SCI-OBS, and the self report version of the two instruments. Agreement between the two versions was very good for the seven SCI-OBS domains (with intraclass correlation coefficients [ICCs] ranging from 0.80 to 0.96) and the four SCI-SHY domains (ICCs from 0.74 to 0.90). When items were analyzed individually, subjects tended to under-report some phobia-related problems in the interview. The total number of items endorsed in the SCI-SHY, but not in the SCI-OBS, was affected by the order of administration: when the SCI-SHY interview was administered first, subjects reported a median of five more symptoms; when the self-report was administered first, there was no significant difference in the number of symptoms endorsed in the two formats. However, this difference is not clinically important, given the large number of items comprising the instruments, and might be explained by the fact that subjects are likely to overemphasize occasional symptoms or behaviors when they are asked by the interviewer to answer a long series of "new" questions as accurately as possible. Given the high agreement between domain scores in the two formats of the instruments and the fact that scores are virtually identical when the self-report is administered first, we recommend the use of the self-report versions in clinical and research settings.