Bipolar Spectrum Disorders in Patients With Cerebellar Lesions A Comparison With Parkinson's Disease Roberto Delle Chiaie, MD,* Amedeo Minichino, MD,* Massimo Salviati, MD,* Samantha Fiorentini, MD,† Angelo Tonini, MD,‡ Francesco Saverio Bersani, MD,* Francesco De Michele, MD,* Maria Caredda, MD,* and Massimo Biondi, MD* Abstract: Nonmotor functions of the cerebellum are well known. Within this frame, the aim of this study was to compare psychiatric morbidity rates among patients affected by cerebellar diseases or Parkinson's disease (PD). Forty-seven patients (27 cerebellar and 20 PD) underwent a comprehensive psychiatric eval- uation (psychopathological rating scales and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders). Psychiatric disorders were slightly more frequent among cerebellar than among PD patients (89% vs. 75%; p = 0.21). Mood disor- ders were more frequent in the cerebellar than in the PD group (90% vs. 55%; p < 0.01). Among those subjects with no psychiatric history prior to the onset of neurological disease, bipolar spectrum disorders were more frequent within the cerebellar group (p < 0.01). These results confirm high rates of psychiatric disorders among cerebellar patients. The higher frequency of bipolar spectrum presentations found in the cerebellar group may suggest a specific involvement of cortico-cerebellar circuits in the pathophysiology of mood dysregulation. Key Words: Bipolar disorder, bipolar spectrum, cerebellum, cerebellar lesions, Parkinson's disease (J Nerv Ment Dis 2015;203: 725–729) T he cerebellum, beyond its role in the control of voluntary move- ments, seems to play a critical role in fine regulation of nonmotor mental processes, such as cognition and emotion (Benson et al., 2008; Berman, 1997; Liotti et al., 2000). A growing body of literature suggests a causal relationship between cerebellar functional and struc- tural abnormalities and psychiatric disorders (Konarski et al., 2005). While most of the evidence investigating this link regards schizophrenia (Picard et al., 2008) and autism (Nayate et al., 2005), less is known about cerebellum involvement in mood disorders. Cerebellar atrophy (Lippmann et al., 1982; Nasrallah et al., 1981), cerebellar gray matter reduction (Moorhead et al., 2007), and smaller vermal subregion V2 and V3 have been found in patients with bipolar disorder when com- pared to healthy subjects (Baldaçara et al., 2011; DelBello et al., 1999; Mills et al., 2005; Monkul et al., 2008). Available evidence points to limbic-related structures being interconnected through the pons with the cerebellar vermis and fastigial nucleus, thus providing a potential neurobiological explanation of these findings (Schmahmann et al., 2004). The aim of the present study has been to investigate the associ- ation between cerebellar disease and psychiatric disorders, trying to focus on whether the development of the mental illnesses in patients with cerebellar dysfunctions may be considered a consequence of the disruption of specific cerebello-cortical circuits or, more simply and specifically, represents a psychological reaction to the persis- tence of long-lasting symptoms associated with the presence of a chronic and disabling neurological disease. METHODS Subjects Forty-seven adult neurological patients (age, 18–65 years) have been recruited at the “Fondazione Santa Lucia” hospital and the “Policlinico Umberto I” University Hospital in Rome. The study group consisted of two groups of patients: 27 with cerebellar lesions (mean age: 50.48 ± 16.09; 51.85% males, 48.15% females; mean duration of illness: 41 ± 12 months) and 20 affected by Parkinson's disease (PD) (mean age: 55.20 ± 12.29; 55% males, 45% females; mean dura- tion of illness: 38 ± 10 months). Cerebellar patients were affected by several types of cerebellar lesions (see Table 1). Inclusion criteria were considered an illness duration of at least 2 years of neurological disease, while exclusion criteria were the existence of a current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV TR) diagnosis of substance use or dependence or having used drugs or alcohol in the 48 hours prior to the examination. Other exclu- sion criteria included: (1) evidence of magnetic resonance imaging (MRI)–documented lesions in cerebral area other than cerebellum and, in particular, MRI-detectable lesions in brain areas typically asso- ciated with major mood disorders, i.e. prefrontal cortex, hippocampus, and amygdala; (2) history of exposure to metabolic or toxic factors known to affect the cerebellum, such as long-term phenytoin use, vita- min B 12 deficiency, or untreated thyroid disease. The study protocol was approved by the institutional review board of Sapienza, University of Rome, and written informed consent was given by all patients before being enrolled. Psychiatric and Neurological Evaluation The diagnoses of cerebellar pathology or PD were based on a thorough clinical and MRI evaluation and were made by a well- trained neurologist specialized in movement disorders (AT). The Berthel Index (Collin et al., 1988), used to assess levels of neurological dis- ability in cerebellar and PD patients (Berthel Index score cerebellar pa- tients: 76.61 ± 16.02; Bethel Index score PD patients: 72.41 ± 13.08), showed that levels of disability in the two subgroups were comparable. Pa- tients were then screened for their present and past psychiatric symptoms, personal, social, and family history. In order to obtain reliable psychiatric diagnoses according to DSM-IV-TR criteria, the Structured Clinical Inter- view for DSM-IV-TR Axis I Disorders (SCID) (First et al., 2002) was ad- ministered to each subject. Psychiatric symptoms, when present, were differently classified whether their onset could be identified as prior or sub- sequent to that of the neurological symptoms. To stratify the experimental sample in psychopathological ho- mogenous subgroups, brief recurrent depressive disorder, minor de- pressive disorder, and dysthymia were grouped together as “not-major unipolar depressions, ” while bipolar and cyclothymic disorders were grouped together as “bipolar spectrum disorders. ” Clinical information about psychiatric symptoms in patients of both groups was obtained with the Hopkins Symptom Checklist (HSCL-90) (Derogatis et al., 1974). *Department of Neurology and Psychiatry, Sapienza University of Rome, Rome; †Dipartimento Salute Mentale, ASL Latina 3, Latina; and ‡IRCCS Fondazione S. Lucia, Rome, Italy. Send reprint requests to Roberto Delle Chiaie, MD, Dipartimento di Neurologia e Psichiatria, “Sapienza” Università di Roma, Via Leone IV 38, (00192) – Roma, Italy. E-mail: r.dellechiaie@centrokahlbaum.it. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0022-3018/15/20309–0725 DOI: 10.1097/NMD.0000000000000359 BRIEF REPORT The Journal of Nervous and Mental Disease • Volume 203, Number 9, September 2015 www.jonmd.com 725 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.