PREMORBID PERSONALITY AS VULNERABILITY FACTOR IN THE DEVELOPMENT OF IMPULSE CONTROL DISORDERS AND PUNDING IN PARKINSON'S DISEASE M.Signorini* , A. Marchetto*, C. Volpato°, and D.Volpe #

Cognitive NeuroPsychology Lab. AFaR - Venice

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*AFaR, Cognitive Neuropsychology Lab. San Raffaele Fatebenefratelli Hospital, Venice, Italy; °IRCCS San Camillo, Venice, Italy # Neuro-rehabilitation Unit, San Raffaele Fatebenefratelli Hospital, Venice, Italy Correspondence to: [email protected]

INTRODUCTION Impulsive and repetitive behaviors, including pathological gambling (PG) and punding, have been recently described in Parkinson’s disease (PD) patients and related to the progression of the disease as well as the adverse effects of anti-parkinsonian treatment, in particular dopamine agonists, which are known to affect the dopaminergic system (Weintraub et al. 2006, Voon et al. 2006, Evans et al. 2004, Silveira-Moriyama et al. 2006). Some clinical features, such as high novelty seeking, age at PD onset and personal or family history of alcohol abuse (Voon et al, 2007), depressive mood, disinhibition, irritability, and appetite disturbances (Pontone et al. 2006) have been also associated to pathological impulsive and repetitive behaviors (PIRB) in PD. In the approach to the behavioral disturbances in PD, the role of the premorbid personality, however, has never been investigated (Stocchi 2005). MATERIALS AND METHODS Subjects included six PD patients with pathological impulsive and repetitive behaviors and 18 PD patients without pathological behaviors (see Tab 1 & 2), recruited at the Center for Rehabilitation of Parkinson's disease of Fatebenefratelli Hospital (Venice) between 2006 and 2009. Permission for the study was obtained from the local research ethical committee and all subjects consented to participate. PD was diagnosed according to conventional clinical signs and evaluated with the Unified Parkinson’s Disease Rating Scale (UPDRS) (Fahn et al. 1987) and the Hoehn–Yahr Scale (Hoehn and Yahr 1967). Patients with motor fluctuations were tested when they were in “on state” and, at the time of the testing, they were regularly taking anti-parkinsonian medications. PIRB weres diagnosed according to DSM-IV-TR criteria (American Psychiatric Association, 2000). Punding was assessed following the clinical characteristics described in literature (Evans et al. 2004). Patients were free of histories of other neurological and psychiatric illness, apart mild anxious and depressive symptoms assessed with Beck Depression Inventory (BDI) (Beck et al. 1961) and State and Trait Anxiety Inventory (STAI X1-X2) (Spielberger et al. 1970). In order to exclude the presence of cognitive deterioration all patients, included PIRB patients, were submitted to the Mini Mental State Examination (MMSE) (Magni et al. 1996) and the Milan Overall Dementia Assessment (MODA) (Brazzelli et al. 1994). Premorbid and current personality of PD patients were assessed as described elsewhere (Hubble et al. 1993, Mendelsohn et al. 1995, Glosser et al. 1995) asking the spouses of each patient to describe how the patient was before the onset of PD (Premorbid Personality) and at the moment of the evaluation (Current Personality) submitting the Big Five Adjectives check list (BFA) (Caprara et al. 2002), a personality assessment tool developed for hetero-evaluation according to the Five Factor Model of Personality (Digman 1990). BFA scores are expressed in T scores. Premorbid and current personality profiles of PD controls group have been compared using paired-samples t test. Scores on BFA PIRB patients have been compared to the PD control group applying the Crawford and Garthwaite modified independent-samples t test (Crawford and Garthwaite 2006). CASE REPORTS •Case #1: male 65 years old. PD diagnosed at age of 44 years. after 15 years of illness he developed a severe yuper-sexuality (HS). (He asked for sex to the wife 10-12 times a day). The onset of HS was not concomitant with dopamine agonist (pramipexole) assumption. The suspension of the dopamine-agonists did not result in remission of behavioral symptoms. •Case #2: female, 57 years old. PD diagnosed at age of 48 years. After 6 years of illness she developed a progressive Compulsive Shopping (CS), spending consistent sums of money, over her economic availability, becoming in debt with bank and friends. When developed CS she assumed levodopa and a dopamine agonist (pramipexole). The onset of CS was not concomitant with changes of anti-parkinsonian drugs. She suspended the dopamine-agonists without any effect on CS. Pathological behavior regressed only after administration of anti-depressive drugs. •Case #3: male, 54 years old. PD diagnosed at age of 40 years. after 13 years of illness she developed an unrestrained interest for embroidery transforming a simple hobby in an uncontrollable and pathological activity without awareness. The absence of anxiety or embarrassment related to excessive applying to embroidery to include this pathological repetitive behavior in the nosological category of punding. More over she developed severe PG playing -poker with significant loss of money. The awareness of this pathological behavior was well present with sense of guilt. onset of behavioral diseases was not concomitant with agonist (pramipexole) assumption. The administration of anti-depressant and anti-psychotic medications was not effective on punding but effective on PG. •Case #4: female, 55 years old. PD diagnosed at age of 45 years. after 8 years of illness she developed a severe PG. The onset of PG was not concomitant with dopamine agonist (pramipexole) assumption. She suspended the dopamine-agonists (Pramipexole) without any effect on PG. Pathological behavior regressed only after administration of anti-depressive (sertralina clorydhrate) drugs. •Case #5: female, 78 years old. She received diagnosis of PD at age of 59. Since the beginning of the disease she developed severe PG playing video-poker with significant loss of money. The awareness of her own pathological behavior was well present with sense of guilt, inadequateness and family conflicts, but she was unable to control this behavior. At the moment of development of PG she assumed a dopamine agonist (pergolide). She suspended the treatment with the dopamine agonist and began the assumption of levodopa without effects on psychopathological behaviors. At the moment of evaluation she assumed only levodopa. •Case #6: female, 59 years old, PD has been diagnosed when she was at age of 50. After 7 years of illness she start to spend a lot of time in modeling activity, producing an enormous quantity of plaster cherubs (more than 1200 in few months), spending all day in this “hobby”. At the moment of development of this behavior she assumed a dopamine agonist (pergolide). She suspended the treatment with the dopamine agonist and began the assumption of levodopa without effects on psychopathological behaviors.

PIRB PERSONALITY EVALUATION At the BFA assessment (see Graphs) showed, in comparison to the sample of PD controls, similar premorbid and current personality profiles in PIRB patients (the controls subjects showed a significant worsening in all dimensions of the personality), suggesting the persistence of a premorbid personality profile. •CASE #1: (very low scores on E, A, ES, OE factors; high scores on C factor). The patient described him self with high morality and conscientiousness, with low flexibility, low emotional stability and asocial traits. •CASE #2: (high scores on E, A, ES, OE factors; low scores on C factor). This profile represent the reverse of the Case 1 and described an idealized self image with low Conscientiousness, low sense of self and its limits, and sens of “grandeur” of self. •CASE #3: (low scores on E, OE factors; high scores on A, C, ES factors). This profile described an intellectualized self image as covering of depressive structure and self centered thoughts. •CASE #4: (high scores on E, A, ES, OE factors; low scores on C factor). This profile described an idealized self image with low conscientiousness, low sense of self and limits, and high need of confirmation and achievement. •CASE #5: (high scores on E, OE factors; low scores on ES factor). This pattern showed idealized self and depressive personality profile. •CASE #6: (high scores on C, ES, OE factors). This profile showed high conscientiousness, emotional stability and openess to experiences: Denial depressive symptoms.

PD CONTROL SUBJECTS BFA scores reported by PD control sample showed a well-balanced premorbid personality profile while the current personality profile was characterized by partial retirement with tendency to inactivity and apathy (Extraversion factor); inclination to act without method and order, low precision and perseverance (Conscientiousness factor); tendency to feel tension, irritability and anxiety (ES factor); low levels of originality and creativity, few culture interests and scarce openness for news (OE factorr). The comparison between premorbid and current personality profiles showed a significant lowering of the scores (paired-samples t test) in four current personality factors: E (t = 3.762, P = .002), Conscientiousness (t = 3.025, P = .008), ES (t = 3.351; P = .004) and OS (t = 2.481; P = .024) while no difference was observed in Agreeableness. The general worsening found in current BFA factors confirmed the results previously reported by Mendelsohn and colleagues (Mendelsohn et al. 1995). DISCUSSION In this study we describe premorbid and current personality profiles of six PD cases with PIRB and 18 PD patients without pathological behaviors as controls. In comparison with PD control group PIRB subjects showed peculiar premorbid personality profile congruent with pathological behavior. In all PIRB cases the pathological behavioral symptoms seemed to be not related to a specific drug effect or modification of the therapy: pathological behaviors remained unvaried when the dopamine agonist assumption was suspended, or after the substitution of dopamine agonists with levodopa. Moreover, all PD patients recruited as controls assumed anti-parkinsonian drugs, included dopamine agonists, but they did not present signs of pathological behaviors. These preliminary data suggest that premorbid personality traits, in concomitance with the progression of the disease, the anti-parkinsonian treatment and other clinical variables, might represent a further vulnerability factor for developing pathological impulsive and repetitive behaviours and might be considered in clinical practice. The retrospective nature of the information about premorbid personality and the limited number of cases here presented allow to advance only a suggestive hypothesis on the role of premorbid personality in developing pathological impulsive and repetitive behaviors in PD and further longitudinal and more extensive researches are needed.

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