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Effects of bilateral stimulation of the subthalamic nucleus on the mean Temperament and Character Inventory–Revised (TCI-R) score in 20 patients with Parkinson disease, 1 month before and 6 and 24 months after surgery.

Effects of bilateral stimulation of the subthalamic nucleus on the mean Temperament and Character Inventory–Revised (TCI-R)23,24 score in 20 patients with Parkinson disease, 1 month before and 6 and 24 months after surgery.

Table 1. Effects of Bilateral Stimulation of the STN on Parkinsonian Disability and Psychiatric and Cognitive Status, 6 and 24 Months After Surgery in 20 PD Patients*
Effects of Bilateral Stimulation of the STN on Parkinsonian Disability and Psychiatric and Cognitive Status, 6 and 24 Months After Surgery in 20 PD Patients*
Table 2. Patients With Psychiatric Disorders According to DSM-IV Criteria Assessed With the MINI*
Patients With Psychiatric Disorders According to DSM-IV Criteria Assessed With the MINI*
Table 3. Effects of Bilateral Stimulation of the STN on PDQ-39 Scores 6 and 24 Months After Surgery in 20 PD Patients*
Effects of Bilateral Stimulation of the STN on PDQ-39 Scores 6 and 24 Months After Surgery in 20 PD Patients*
Table 4. Effects of Continuous Bilateral Stimulation of the STN on SAS Scores 6 and 24 Months After Neurosurgery in 20 PD Patients*
Effects of Continuous Bilateral Stimulation of the STN on SAS Scores 6 and 24 Months After Neurosurgery in 20 PD Patients*
Original Contribution
August 2006

Subthalamic Stimulation in Parkinson Disease: Behavior and Social Adaptation

Author Affiliations

Author Affiliations: Centre d’Investigations Cliniques (Drs Houeto, Mesnage, Gargiulo, Torny, Welter, and Agid and Ms Béhar), Research Unit 7593 (Drs Mallet and Pelissolo), and Service de Biostatistiques et Information Médicale (Dr Tezenas du Montcel), Hôpital de la Salpêtrière, Paris, France; and Service de Neurologie, Poitiers University Hospital, Poitiers, France (Drs Houeto and Mesnage).

Arch Neurol. 2006;63(8):1090-1095. doi:10.1001/archneur.63.8.1090

Background  Bilateral subthalamic high-frequency stimulation significantly improves motor functions in patients with advanced forms of Parkinson disease (PD). This favorable effect contrasts with a growing number of reports that the treatment may result in psychiatric complications.

Objective  To analyze the presence of behavioral disorders and social maladjustment in PD patients successfully treated with continuous bilateral subthalamic stimulation.

Design  Prospective study.

Setting  University hospital.

Methods  Twenty PD patients underwent prospective evaluation for behavioral and personality changes, quality of life, and social functioning, 6 and 24 months after surgery to implant bilateral stimulating electrodes within the subthalamic nucleus.

Results  At 6 and 24 months after surgery, parkinsonian motor disability (on-stimulation/off-medication) was improved by 81% and 67%, respectively, and the severity of levodopa-related motor complications was improved by 84% and 70%, respectively. Levodopa-equivalent dosage was decreased by 79% and 66%, respectively; severity of depression was improved by 21% and 33%, respectively; and severity of anxiety was improved by 43% and 64%, respectively. The patients' personality traits were unmodified. Twenty-four months after surgery, the global score for quality of life was improved by 28%, whereas scores for social adjustment remained stable.

Conclusions  Provided that patients with PD are rigorously selected for neurosurgery, subthalamic stimulation (1) improves mood, anxiety, and quality of life; (2) does not result in severe permanent psychiatric disorders or modify patients' personality; and (3) does not ameliorate social adaptation.

Bilateral high-frequency stimulation of the subthalamic nucleus (STN) is recognized as the treatment of choice for advanced levodopa-responsive forms of Parkinson disease (PD).1 This technique leads to a reduction in the severity of parkinsonian motor disability and levodopa-induced motor complications by 60% to 80%, enables the daily dosage of levodopa to be reduced by 40% to 80%,1-3 and has little or no effect on cognitive function,4,5 provided patients are correctly selected.6 This favorable effect on motor and cognitive functions contrasts with a growing number of reports that the treatment may result in psychiatric complications. Transient mania,7,8 depression with increased suicidal risk,9,10 pseudobulbar crying,11 anxiety, and severe behavioral disorders12 have been reported. However, the retrospective nature of the studies, the limited number of patients undergoing analysis, and the lack of systematic psychiatric assessments make it difficult to draw any general conclusions from these reports. The present study was undertaken to prospectively analyze the effects of bilateral stimulation of the STN on personality, quality of life, the behavioral profile, and social adaptation in a selected sample of 20 levodopa-responsive patients with PD (hereafter referred to as PD patients).


We prospectively studied 20 PD patients (13 women and 7 men; mean ± SD age, 54.9 ± 10.3 years) who consecutively underwent surgery between January 1, 2001, and March 31, 2002, for bilateral placement of stimulating electrodes within the STN. Selection criteria for surgery6 included an advanced form of the disease (Hoehn and Yahr13 score after ≥12-hour interruption of antiparkinsonian medication therapy [off-medication condition], >3; mean ± SD Unified Parkinson's Disease Rating Scale [UPDRS] part III score,14 42.4 ± 15.4; and mean ± SD disease duration, 13.7 ± 6.1 years); levodopa-induced improvement in the motor disability score of more than 50% (mean ± SD improvement in the UPDRS part III score, 83% ± 10%); presence of severe levodopa-induced motor complications (mean ± SD UPDRS part IV score, 8 ± 2) despite optimized medical treatment (mean ± SD levodopa-equivalent15 daily dosage, 1320 ± 560 mg/d); and absence of cognitive impairment (score for the Mattis Dementia Rating Scale,16 ≥135). Patients with the following psychiatric disorders were excluded: severe Axis II disorders (as shown by a nonstandardized psychiatric interview), substance abuse, psychosis predating the levodopa or dopamine agonist treatment, bipolar I disorder, and untreated severe depression.

All the patients received a bilateral stereotactic STN implant, as previously described.17,18 Clinical evaluation was performed 1 month before (ie, at baseline) and 6 and 24 months after surgery. One patient was no longer living in France at the end of the study and could not be examined.

Evaluation of motor disability (UPDRS part III)14 was performed in the off-medication state, as defined by the Core Assessment Program for Intracerebral Transplantations,19 and in the best on-medication condition after the administration of a single suprathreshold dose of levodopa. After surgery, parkinsonian motor disability (UPDRS part III) was evaluated in the on-stimulation/off-medication condition using the long-term stimulation variables. The severity of levodopa-related complications was evaluated using the UPDRS part IV.14 Cognitive functions were assessed using the Mattis Dementia Rating Scale for global cognitive assessment16 and a 50-point frontal lobe dysfunction scale, including the Wisconsin Card Sorting Test, verbal fluency, and motor and graphic sequences.5

Psychopathological features were assessed by 2 different investigators, as described elsewhere.12 A semistructured psychiatric interview (Mini-International Neuropsychiatric Inventory20), which explored the principal psychiatric disorders, was performed by one of us (C.B.), along with the evaluation of mood and anxiety using the Montgomery Asberg Depressive Rating Scale21 and the Brief Scale for Anxiety.22 To further evaluate the behavior and psychiatric profile of each patient, a nonstandardized psychiatric interview was performed by another investigator (L.M.), who was blinded to the results of the Mini-International Neuropsychiatric Inventory. The results of these examinations were compared to determine whether the responses were reliable and to make a tentative diagnosis. In addition, personality was assessed using a French version23 of the Temperament and Character Inventory–Revised, a 260-item, self-administered, true-false questionnaire24 to assess the dimensions of personality (novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence).

Quality of life was evaluated using a validated French version25 of the 39-item Parkinson's Disease Questionnaire26; social adaptation was evaluated using the Social Adjustment Scale.27 The Social Adjustment Scale is a semistructured interview, performed in the presence of the spouse, that evaluates current social adjustment in terms of 44 items. These are classified into the following 5 main sections: work, social life and leisure activities, family life, marital relations, and interaction with children. Each item, rated from 1 to 5 (excellent to bad), permits an estimation of “efficiency,” “interpersonal behavior,” and “disagreement-conflict.” An additional section explores the global adjustment score according to the opinion of the interviewer (M.G.).

We compared scores at baseline and 24 months after surgery using a paired Wilcoxon rank sum test. We chose this nonparametric test because of the small sample size and the nonnormally distributed data. P<.05 was considered statistically significant. Data obtained at 6 months are included in Tables 1, 2, 3, and 4. Statistical analyses were performed using SAS statistical software, version 8.1 (SAS Institute Inc, Cary, NC).


Twenty-four months after neurosurgery, the severity of parkinsonian motor disability (on-stimulation/off-medication condition) was decreased by 67%, the severity of levodopa-related motor complications was decreased by 70%, and the levodopa-equivalent daily dosage was decreased by 66% compared with the preoperative state (Table 1). The cognitive status (Mattis Dementia Rating Scale and frontal lobe dysfunction scale scores) was not significantly modified. Compared with the preoperative state, bilateral STN stimulation significantly improved the Montgomery Asberg Depressive Rating Scale score by 33% and the Brief Scale for Anxiety score by 64%, 24 months after neurosurgery (Table 1).

Nine of 20 patients had experienced depressive episodes during the course of the disease before surgery (Table 2). During the 6 months after surgery, a depressive episode was observed in 4 patients, 2 of whom had no history of depression. The first, a 54-year-old man with an 8-year history of PD (levodopa-equivalent dosage, 1800 mg/d), developed sad mood, loss of initiative, and dissatisfaction, despite a 95% improvement of his parkinsonian motor disability. Depression resolved within 3 weeks after levodopa therapy (500 mg/d) was reintroduced. The second patient, a 59-year-old woman, developed a severe depressive state after the death of her caregiver and was still depressed 24 months after stimulation.

Two patients had a history of hypomania, one of whom experienced a transient episode of hypomania at the time of the surgery. In 2 other patients with no history of mood disorders, a transient hypomanic state was observed, 6 months after surgery in one case (which resolved with reduction of the daily dosage of dopamine agonists) and 24 months after surgery in the other (which resolved spontaneously).

Agoraphobia, which was present in 4 patients before surgery, had disappeared 6 months after surgery in 2 cases. Agoraphobia recurred 24 months after surgery in the other 2 patients: one had a mild freezing of gait incompletely controlled by surgery and the other had a mild persistent tremor. Social phobia, observed in 3 patients 1 month before surgery, had disappeared 6 months after surgery and had reappeared 24 months after surgery in the 3 patients, including the 2 who had an intermittent recurrence of mild tremor or freezing of gait. Generalized anxiety, obsessive-compulsive, panic, and posttraumatic stress disorders were dramatically improved 6 months after surgery, and this favorable effect was maintained or amplified 24 months after surgery (Table 2).

Patients' quality of life (Parkinson's Disease Questionnaire) was significantly improved by 28% at 24 months after neurosurgery (Table 3). Four domains of the Parkinson's Disease Questionnaire score (mobility, activities of daily living, stigmata, and bodily discomfort) were significantly improved, whereas 4 other domains (emotional well-being, social support, cognition, and communication) were not. The Social Adjustment Scale global score and subscores (work, social life and leisure activities, family life, marital relations, and interaction with children) were not modified by STN stimulation 24 months after neurosurgery (Table 4). There was no change in the scores for personality traits as evaluated by the Temperament and Character Inventory–Revised 24 months after STN stimulation compared with the preoperative state (Figure).

Continuous monopolar electrical stimulation (20 patients, 40 electrodes; mean ± SD of 2.75 ± 0.4 V was applied through 1 [n = 35] or 2 [n = 5] contacts with a mean ± SD frequency of 144 ± 27 Hz and a pulse width of 60 microseconds [n = 37] or 90 microseconds [n = 3]). Transient treatment-related adverse effects included a leg venous thrombosis that resolved after 3 months of treatment with anticoagulants (n = 1), infection of the stimulator area that resolved after antibiotic treatment and temporary removal of the stimulator (n = 1), and stimulation-induced hypophonia ameliorated by adjunction of dopaminergic treatment (n = 2). Permanent adverse effects included eyelid-opening apraxia (n = 2); persistence of disabling dyskinesias related to dopaminergic treatment, subthalamic stimulation, or both (n = 2); and significant weight gain (>10 kg; n = 2).


In this prospective study, performed in a selected sample of patients with severe levodopa-responsive forms of PD who underwent surgery for bilateral stimulation of the STN, we found an unexpected contrast between the marked improvement in parkinsonian motor disability, mood disorders, and anxiety, without any personality or cognitive changes, and the poor personal and sociofamilial adaptation.

The long-term favorable effect of STN stimulation on mood (Table 2) is consistent with 2 previous results,29,30 showing that mild to moderate depression could benefit from long-term STN stimulation. None of the patients with postoperative depression have had suicide attempts as occurred in 25% of patients in another study.10 Although the possibility of a premorbid psychiatric condition cannot be excluded in the latter study,12 the high postoperative proportion of suicide attempts is unexpected. Because suicide attempts are known to be associated with impulsivity,30 it may be hypothesized that inappropriate or exaggerated behaviors could occur as a result of impaired emotional responses to external or cognitive stressors when stimulation directly affects limbic neuronal circuits related to the STN.31

The robust improvement of anxiety traits observed 24 months after surgery (Table 2) is in agreement with a previous report30 but contrasts with the results of another study in which general anxiety was aggravated postoperatively.12 The retrospective nature of the latter study, along with the particular psychopathology of the population studied, may account for this discrepancy. Several factors may have contributed to the favorable effect of STN stimulation on anxiety, a result that has also been reported after pallidal stimulation.32 The improvement of anxiety may be ascribed to the amelioration of motor symptoms, owing to the close temporal relationship between anxiety and motor fluctuations and the beneficial effects of levodopa therapy on anxiety.33 Another possibility is that anxiety, known to coexist with depression in PD,34 improved as a result of the amelioration of mood disorders (Table 2). Finally, it cannot be excluded that the improvement of anxiety resulted from the direct modulation of anxiety-related neuronal systems.35

We failed to detect postoperative personality changes in our patients (Figure) and thus conclude that STN stimulation does not contribute per se to permanent psychiatric disorders, provided that patients are carefully selected (ie, in the absence of depression or a history of severe personality disorders) and the postoperative medical management is adequately performed.30 In line with the results of a previous study,12 however, patients with substance abuse were excluded. The fact that a recent report suggested that patients with dopamine replacement therapy dependence may benefit from stimulation36 suggests that further studies are needed to clarify this issue.

Despite the marked postoperative improvement in motor disability, the patients' quality of life was only moderately ameliorated. The 28% amelioration of the Parkinson's Disease Questionnaire summary index mainly resulted from the improvement of items related to parkinsonian motor disability, whereas items unrelated to mobility were not improved (Table 3), a finding that is consistent with another report.37 Moreover, the personal, familial, professional, and social adaptation of patients was unexpectedly unchanged 24 months after neurosurgery compared with the preoperative state (Table 4). The reasons for the absence of amelioration of patients' social adjustment are unclear. Factors such as cognitive impairment, psychiatric disorders, or personality changes triggered postoperatively are not contributive (Table 2 and Figure). Although patients were in a state of well-being (Table 4), the occurrence of apathy in some patients cannot be excluded, as previously suggested.29,30 Nevertheless, it is our impression that other possible causes should also be taken into consideration, such as the preoperative psychological and sociological status of the patients.


Provided that patients with PD are carefully selected, in particular without a history of severe personality disorders, (1) we confirm the remarkable efficacy of bilateral STN stimulation on parkinsonian motor disability, without modifications of the general cognitive status of patients; (2) we show that STN stimulation does not induce permanent or severe psychiatric adverse effects or modification of patients' personality, and that it helps to ameliorate mood disorders and anxiety; and (3) we show that neurosurgery is accompanied by an improvement in quality of life that does not significantly change patients' personal and socioprofessional adaptation. The latter result, which will need to be confirmed in a larger series of patients, points to the necessity of careful preoperative analysis of the motor, intellectual, and psychiatric profile of patients and their personal, familial, and socioprofessional status to help them to anticipate their psychological and social situation after surgery.

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Article Information

Correspondence: Yves Agid, MD, PhD, Centre d’Investigations Cliniques, Hôpital de la Salpêtrière, 47 Boulevard de l’Hôpital, 75013 Paris, France (

Accepted for Publication: February 8, 2006.

Author Contributions:Study concept and design: Houeto, Mallet, Mesnage, and Agid. Acquisition of data: Houeto, Mallet, Mesnage, Béhar, Gargiulo, Torny, Pelissolo, and Welter. Analysis and interpretation of data: Houeto, Mallet, Mesnage, Tezenas du Montcel, Pelissolo, and Agid. Drafting of the manuscript: Houeto, Mesnage, and Agid. Critical revision of the manuscript for important intellectual content: Mallet, Tezenas du Montcel, Béhar, Gargiulo, Torny, Pelissolo, and Welter. Statistical analysis: Tezenas du Montcel and Pelissolo. Obtained funding: Agid. Administrative, technical, and material support: Houeto and Mallet. Study supervision: Houeto, Mallet, and Agid.

Funding/Support: This study was supported by the Fondation pour la Recherche Médicale (France).

Acknowledgment: We thank A. M. Bonnet, MD, P. Cornu, MD, D. Dormont, MD, S. Navarro, MD, B. Pidoux, MD, PhD, and B. Pillon, PhD, who performed the neurosurgical procedures, and the nurses of the Centre d’Investigations Cliniques, who cared for the patients during the study.

Limousin  PKrack  PPollak  P  et al.  Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease.  N Engl J Med 1998;3391105- 1111PubMedGoogle ScholarCrossref
Houeto  JLDamier  PBejjani  PB  et al.  Subthalamic stimulation in Parkinson's disease: a multidisciplinary approach.  Arch Neurol 2000;57461- 465Google ScholarCrossref
Molinuevo  JLValldeoriola  FTolosa  E  et al.  Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson's disease.  Arch Neurol 2000;57983- 988PubMedGoogle ScholarCrossref
Ardouin  CPillon  BPeiffer  E  et al.  Bilateral subthalamic or pallidal stimulation affects neither memory nor executive functions: a series of 62 patients.  Ann Neurol 1999;46217- 223PubMedGoogle ScholarCrossref
Pillon  BArdouin  CDamier  P  et al.  Neuropsychological changes between “off” and “on” STN or GPi stimulation in Parkinson's disease.  Neurology 2000;55411- 418PubMedGoogle ScholarCrossref
Welter  MLHoueto  JLTezenas du Moncel  S  et al.  Clinical predictive factors of subthalamic stimulation in Parkinson's disease.  Brain 2002;125575- 583PubMedGoogle ScholarCrossref
Kulisevsky  JBerthier  MLGironell  A  et al.  Mania following deep brain stimulation for Parkinson's disease.  Neurology 2002;591421- 1424PubMedGoogle ScholarCrossref
Romito  LMRaja  MDaniele  A  et al.  Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease.  Mov Disord 2002;171371- 1374Google ScholarCrossref
Doshi  PKChhaya  NBhatt  MH Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson's disease.  Mov Disord 2002;171084- 1085PubMedGoogle ScholarCrossref
Berney  AVingerhoets  FPerrin  A  et al.  Effect on mood of subthalamic DBS for Parkinson's disease: a consecutive series of 24 patients.  Neurology 2002;591298- 1299Google ScholarCrossref
Okun  MSRaju  DVWalter  BL  et al.  Pseudobulbar crying induced by stimulation in the region of the subthalamic nucleus.  J Neurol Neurosurg Psychiatry 2004;75921- 923Google ScholarCrossref
Houeto  JLMesnage  VMallet  L  et al.  Behavioural disorders, Parkinson's disease and subthalamic stimulation.  J Neurol Neurosurg Psychiatry 2002;72701- 707PubMedGoogle ScholarCrossref
Hoehn  MMYahr  MD Parkinsonism: onset, progression and mortality.  Neurology 1967;17427- 442PubMedGoogle ScholarCrossref
Fahn  SElton  RLUPDRS Development Committee Unified Parkinson's Disease Rating Scale.  In: Fahn  S, Marsden  CD, Calne  D, et al, eds. Recent Development in Parkinson's Disease.Vol 2. Florham Park, NJ: Macmillan Healthcare Information; 1987:153-163
Krack  PPollak  PLimousin  P  et al.  Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease.  Brain 1998;121451- 457PubMedGoogle ScholarCrossref
Mattis  S Dementia Rating Scale.  Odessa, Fla: Psychological Assessment Resources; 1988
Bejjani  BPDormont  DPidoux  B  et al.  Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance.  J Neurosurg 2000;92615- 625PubMedGoogle ScholarCrossref
Houeto  JLWelter  MLBejjani  BP  et al.  Subthalamic stimulation in Parkinson's disease: intraoperative predictive factors.  Arch Neurol 2003;60690- 694PubMedGoogle ScholarCrossref
Langston  JWWidner  HGoetz  CG  et al.  Core assessment program for intracerebral transplantations (CAPIT).  Mov Disord 1992;72- 13PubMedGoogle ScholarCrossref
Sheehan  DVLecrubier  YSheehan  KH  et al.  The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.  J Clin Psychiatry 1998;59(suppl 20)22- 57Google Scholar
Montgomery  SAAsberg  M A new depression scale designed to be sensitive to change.  Br J Psychiatry 1979;134382- 389PubMedGoogle ScholarCrossref
Tyrer  POwen  RTCichetti  DV The brief scale for anxiety: a subdivision of the Comprehensive Psychopathological Rating Scale.  J Neurol Neurosurg Psychiatry 1984;47970- 975PubMedGoogle ScholarCrossref
Pelissolo  AMallet  LBaleyte  J-M  et al.  The Temperament and Character Inventory–Revised (TCI-R): psychometric characteristics of the French version.  Acta Psychiatr Scand 2005;112126- 133PubMedGoogle ScholarCrossref
Cloninger  CRSvrakic  DMPrzybeck  TR A psychobiological model of temperament and character.  Arch Gen Psychiatry 1993;50975- 990PubMedGoogle ScholarCrossref
Auquier  PSapin  CZiegler  M  et al.  Validation of the French language version of the Parkinson's Disease Questionnaire—PDQ-39 [in French].  Rev Neurol (Paris) 2002;15841- 50PubMedGoogle Scholar
Peto  VJenkinson  CFitzpatrick  RGreenhall  R The development and validation of a short measure of functioning and well being for individuals with Parkinson's disease.  Qual Life Res 1995;4241- 248PubMedGoogle ScholarCrossref
Weissman  MM The assessment of social adjustment: a review of techniques.  Arch Gen Psychiatry 1975;32357- 365PubMedGoogle ScholarCrossref
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.  Washington, DC: American Psychiatric Association; 1994
Daniele  AAlbanese  AContarino  MF  et al.  Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson's disease.  J Neurol Neurosurg Psychiatry 2003;74175- 182PubMedGoogle ScholarCrossref
Funkiewiez  AArdouin  CCaputo  E  et al.  Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson's disease.  J Neurol Neurosurg Psychiatry 2004;75834- 839PubMedGoogle ScholarCrossref
Stefurak  TMikulis  DMayberg  H  et al.  Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.  Mov Disord 2003;181508- 1516PubMedGoogle ScholarCrossref
Higginson  CIFields  JATroster  AI Which symptoms of anxiety diminish after surgical interventions for Parkinson disease?  Neuropsychiatry Neuropsychol Behav Neurol 2001;14117- 121PubMedGoogle Scholar
Maricle  RANutt  JGValentine  RJCarter  JH Dose-response relationship of levodopa with mood and anxiety in fluctuating Parkinson's disease: a double-blind, placebo-controlled study.  Neurology 1995;451757- 1760PubMedGoogle ScholarCrossref
Walsh  KBennett  G Parkinson's disease and anxiety.  Postgrad Med J 2001;7789- 93PubMedGoogle ScholarCrossref
Mallet  LMesnage  VHoueto  JL  et al.  Compulsions, Parkinson's disease, and stimulation.  Lancet 2002;3601302- 1304PubMedGoogle ScholarCrossref
Witjas  TBaunez  CHenri  JM  et al.  Addiction in Parkinson's disease: impact of subthalamic nucleus deep brain stimulation.  Mov Disord 2005;201052- 1055PubMedGoogle ScholarCrossref
Martinez-Martin  PValldeoriola  FTolosa  E  et al.  Bilateral subthalamic nucleus stimulation and quality of life in advanced Parkinson's disease.  Mov Disord 2002;17372- 377PubMedGoogle ScholarCrossref