Parkinson Disease: Leentjens AF

Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK. · Mov Disord. · Pubmed #17394234 links to  free full text

Abstract: Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

Starkstein SE, Leentjens AF. · School of Psychiatry, University of Western Australia, WA, Australia. · J Neurol Neurosurg Psychiatry. · Pubmed #18187477 No free full text.

Abstract: Apathy is increasingly recognised as a common behavioural syndrome in psychiatric disorders, but it is conceptually ill defined. The aim of this study was to examine the concept of apathy as it is currently used in neurology and psychiatry, by review of the literature and conceptual analysis. There is no consensus on diagnostic criteria for apathy as a syndrome. Apathy is mostly defined as a disorder of motivation, and operationalised as diminished goal oriented behaviour and cognition. There is discussion about whether an emotional dimension should form part of the definition of apathy. Abulia is considered a more severe type of apathy, but its nosological position is still unclear. A structured clinical interview and a proposal for diagnostic criteria for apathy in dementia have been recently validated. There are several valid and reliable scales to measure the severity of apathy in patients with psychiatric and neurological disorders. In summary, apathy is increasingly recognised as a common behavioural syndrome associated with neuropsychiatric disorders. There is a need for consensus on diagnostic criteria to facilitate future research. From a nosological perspective, future studies should examine the overlap with other psychiatric and neurodegenerative conditions and further validate specific diagnostic and assessment tools.

Reijnders JS, Ehrt U, Weber WE, Aarsland D, Leentjens AF. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Mov Disord. · Pubmed #17987654 No free full text.

Abstract: Prevalence rates of depressive disorders in Parkinson's disease (PD) vary widely across studies, ranging from 2.7% to more than 90%. The aim of this systematic review was to calculate average prevalences of depressive disorders taking into account the different settings and different diagnostic approaches of studies. Using Medline on Pubmed, a systematic literature search was carried out for studies of depression in Parkinson's disease. A total of 104 articles were included and assessed for quality; 51 articles fulfilled the quality criteria. Multiple publications from the same database were not included in the meta-analysis. In the remaining 36 articles, the weighted prevalence of major depressive disorder was 17% of PD patients, that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms, irrespective of the presence of a DSM defined depressive disorder, were present in 35%. In studies using a (semi) structured interview to establish DSM criteria, the reported prevalence of major depressive disorder was 19%, while in studies using DSM criteria without a structured interview, the reported prevalence of major depressive disorder was 7%. Population studies report lower prevalence rates for both major depressive disorder and the clinically significant depressive symptoms than studies in other settings. This systematic review suggests that the average prevalence of major depressive disorder in PD is substantial, but lower than generally assumed.

Scholtissen B, Verhey FR, Steinbusch HW, Leentjens AF. · Department of Psychiatry and Neuropsychology, Institute of Brain and Behaviour, Maastricht University, Maastricht, The Netherlands. · J Neural Transm. · Pubmed #16252066 No free full text.

Abstract: Parkinson's disease (PD) is a neuropsychiatric disease affecting approximately 1-2% of the general population. The classical triad of symptoms, tremor, rigidity, and bradykinesia is mainly caused by degeneration of dopaminergic neurons from the substantia nigra. However, other neurotransmitter systems also show signs of degeneration, among which the serotonergic system. The exact role of serotonin in PD remains unclear. We present here a review about functional serotonergic interventions and serotonergic imaging studies in PD, and will go into the importance of combining preclinical and clinical research data in order to gain more insight into the role of serotonin in PD. More specifically, the present review is aimed at bridging the gap between data from animal models of PD and data from human research.

Leentjens AF. · Department of Psychiatry, Maastricht University Hospital, PO Box 5800, 6202 AZ, the Netherlands. · J Geriatr Psychiatry Neurol. · Pubmed #15312275 No free full text.

Abstract: BACKGROUND: Depression frequently accompanies Parkinson's disease (PD) and may have a negative impact on activities of daily living, cognitive performance, and quality of life. Because of the symptom overlap between the 2 disorders, it may be difficult to recognize depression in PD. Moreover, the partially shared pathophysiology may make it difficult to treat depressive symptoms without influencing motor or cognitive function. OBJECTIVE: To review the current knowledge of the epidemiology, etiology, pathophysiology, and treatment of depression in patients with Parkinson's disease. METHOD: Discussion of recent studies and relevant literature. CONCLUSION: Not only conceptually but also in terms of etiology, pathophysiology, and treatment, the relationship between PD and depression remains a challenge. There are still many questions to be answered. In the therapeutic domain, large, placebo-controlled trials are necessary to evaluate the efficacy of antidepressant treatment and allow the development of evidence-based guidelines.

Scholtissen B, Verhey FR, Adam JJ, Weber W, Leentjens AF. · Institute of Brain and Behaviour, Maastricht University Hospital, Maastricht, The Netherlands. · Clin Neuropharmacol. · Pubmed #16960473 No free full text.

Abstract: BACKGROUND: Parkinson disease (PD) is a neuropsychiatric disease that is characterized by motor and neuropsychiatric symptoms. Multiple neurotransmitter systems, including the serotonergic system, are involved in the pathophysiology of this disease. The exact role of the serotonergic system in PD is still unclear. OBJECTIVE: To investigate the role of serotonin on specific aspects of cognition, mood, and motor performance in PD. METHODS: In a double-blind, randomized, placebo-controlled, crossover design, the effects of a nonspecific serotonergic challenge with citalopram, a selective serotonin reuptake inhibitor, and a 5-HT1a receptor-specific challenge with buspirone on the Visual Verbal Learning Task, Concept Shifting Task, Profile of Mood State Questionnaire, motor section of the Unified Parkinson Disease Rating Scale (section 3), Simple Reaction Time Task, and Finger Precuing Task were studied in 21 PD patients in early stages of their disease and 21 age-, sex-, and education-matched healthy volunteers. RESULTS: The serotonergic challenges resulted in similar effects for both groups. No changes of scores on the cognitive tasks (Visual Verbal Learning Task and Concept Shifting Task) were observed. Results of the Profile of Moods State Questionnaire indicated that, at baseline, PD patients scored less than controls on all 5 subscales. Motor performance (measured by reaction time) was negatively affected by the interventions. CONCLUSIONS: The effects of nonspecific and 5-HT1a receptor-specific challenging of the serotonergic neurotransmitter system had similar effects in both PD patients and healthy control subjects. These findings indicate that serotonergic function is not impaired in early PD and that serotonin, although involved in the pathophysiology of PD, does not seem to play a direct role in cognition, mood, and motor performance in PD patients, but may be involved in hypokinesia.

Scholtissen B, Verhey FR, Adam JJ, Prickaerts J, Leentjens AF. · Institute of Brain and Behaviour, Maastricht University, P.O. Box 616 6200 MD Maastricht, The Netherlands. · J Neurol Sci. · Pubmed #16756999 No free full text.

Abstract: BACKGROUND: Parkinson's disease (PD) is a neuropsychiatric disease, which is not only characterized by motor symptoms, but also by cognitive and psychiatric symptoms. It is hypothesized that some of the non-motor symptoms are related to the serotonergic deficiency that is present in PD. AIM: To study the influence of serotonin on cognition, memory and motor performance in PD. METHODS: In a double blind, randomized, placebo-controlled, cross-over design, the effect of acute tryptophan depletion (ATD) on the Visual Verbal Learning Task (VVLT), the Concept Shifting Task (CST), Simple Reaction Time Task (SRT), Finger Precuing Task (FPT) and the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS, Section 3) was investigated in 15 PD patients in early stages of their disease and 15 healthy volunteers, matched for age, sex and educational status. RESULTS: With the exception of the absence of a differential effect for PD patients with the long interval of the SRT, ATD produced similar effects in PD patients and control subjects on all tasks. These included impairment of delayed recall and delayed recognition on the VVLT, and improved SRT and FPT for 'short intervals'. The UPDRS in patients remained unaffected after ATD. CONCLUSION: Serotonin does not appear to play a disease-specific role in cognition and reaction time in early stage PD patients, nor does acute reduction of cerebral serotonin levels affect motor symptoms in a clinically relevant way.

Leentjens AF, Vreeling FW, Luijckx GJ, Verhey FR. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Int J Geriatr Psychiatry. · Pubmed #12789682 No free full text.

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Leentjens AF, Koester J, Fruh B, Shephard DT, Barone P, Houben JJ. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Clin Ther. · Pubmed #19243709 No free full text.

Abstract: BACKGROUND: Mood and motivational symptoms have been reported in up to 35% and 51%, respectively, of patients with Parkinson's disease (PD). Preliminary evidence indicates that pramipexole may have a positive effect on these symptoms. OBJECTIVE: This analysis was conducted to evaluate the effects of pramipexole on mood and motivational symptoms in patients with PD. METHODS: Data for the meta-analysis were extracted from all randomized, double-blind, placebo-controlled trials of pramipexole in the manufacturer's database that included part I of the Unified Parkinson's Disease Rating Scale (UPDRS) as an outcome measure. Only patients with baseline scores >0 (range, 0-4) on item 3 (mood) and item 4 (motivation) were included. Separate analyses were performed for mood and motivational symptoms. The outcome of interest was improvement in scores, with no improvement including both unchanged and increased scores. Odds ratios (ORs), 95% CIs, and Cochran-Mantel-Haenszel tests were calculated to compare rates of improvement and no improvement, stratified by trial. RESULTS: Fourteen randomized, double-blind, placebo-controlled trials of pramipexole were identified, all employing the severity of motor symptoms of PD as a primary outcome. Seven of these trials (N = 1296) employed part I of the UPDRS as a secondary outcome measure and were included in the meta-analysis; no other measure of mood or motivational symptoms was used in any of the 14 studies. Six of the 7 studies included patients with motor fluctuations due to levodo-pa treatment, and the remaining study included patients who did not yet require levodopa. Six studies were published in peer-reviewed journals, and all 7 were included in the New Drug Application for pramipexole. The published study reports were usually limited to motor symptoms; only 1 reported on mood and motivation. However, for the purpose of this meta-analysis, the authors had access to data that were not reported in the original publications. In the pooled data set, 480 patients (59.8% male; mean age, 63.3 years) had a baseline score >0 on item 3 (mood). These mood symptoms improved in 64.7% of patients treated with pramipexole and 43.4% of those receiving placebo (OR weighted by trial = 2.41; P < 0.001). Five hundred seventy patients (64.9% male; mean age, 64.1 years) had a baseline score >0 on item 4 (motivation). These motivational symptoms improved in 63.2% of patients treated with pramipexole and 45.0% of those receiving placebo (OR weighted by trial = 2.06; P < 0.001). CONCLUSIONS: This meta-analysis of 7 randomized controlled trials suggests that pramipexole had a beneficial effect on mood and motivational symptoms in PD patients who did not have major depressive disorder. The clinical value of pramipexole in the treatment of depressive and apathetic syndromes requires further investigation.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, the Netherlands. · Mov Disord. · Pubmed #18792121 links to  free full text

Abstract: Anxiety syndromes are common in patients with Parkinson's disease (PD) with up to 30% suffering from panic disorder, and up to 11% from generalized anxiety disorder (GAD). Anxiety is associated with increased subjective motor symptoms, more severe gait problems, dyskinesias, freezing, and on/off fluctuations. Anxiety has a negative impact on health related quality of life and is strongly associated with depressive syndromes. Since a variety of anxiety scales have been used in PD patients, the Movement Disorder Society commissioned a task force to assess the clinimetric properties of these scales in PD. A systematic review was conducted to identify anxiety scales that have either been validated or used in patients with PD. Six anxiety rating scales were identified. These were the Beck anxiety inventory, the hospital anxiety and depression scale, the Zung self-rating anxiety scale and anxiety status inventory, the Spielberger state trait anxiety inventory, and the Hamilton anxiety rating scale. In addition, Item 5 (anxiety) of the neuropsychiatric inventory was included in the review. No scales met the criteria to be "recommended," and all scales were classified as "suggested." Essential clinimetric information is missing for all scales. Because several scales exist and have been used in PD, the task force recommends further studies of these instruments. If these studies show that the clinimetric properties of existing scales are inadequate, development of a new scale to assess anxiety in PD should be considered.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Mov Disord. · Pubmed #18709683 links to  free full text

Abstract: Apathy is a common condition in Parkinson's disease (PD) and is generally defined as a lack of motivation. It is associated with more severe cognitive dysfunction and a decrease in activities of daily living (ADL) performance. Anhedonia, the inability to experience pleasure, can be a symptom of both depressive and apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of apathy and anhedonia scales in PD patients. A systematic literature review was conducted to identify scales that have either been validated or used in PD patients. Apathy scales identified for review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition, item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were included. Anhedonia scales identified for review were the Snaith-Hamilton Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia. Only the AS is classified as "recommended" to assess apathy in PD. Although item 4 of the UPDRS also meets the criteria to be classified as recommended, it should be considered for screening only because of the obvious limitations of a single item construct. For the assessment of anhedonia, only the SHAPS meets the criteria of "Suggested." Information on the validity of apathy and anhedonia scales is limited because of the lack of consensus on diagnostic criteria for these conditions.

Leentjens AF, Driessen G, Weber W, Drukker M, van Os J. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Neuroepidemiology. · Pubmed #18277080 No free full text.

Abstract: BACKGROUND/AIM: Parkinson's disease (PD) is often complicated by psychiatric comorbidity, which is likely to lead to a higher use of mental health care facilities. In addition, psychiatric symptomatology and associated mental health care use may be present even before motor symptoms and PD are diagnosed, as the pathophysiology of PD and its psychiatric consequences are likely to overlap to a degree. This will be reflected in an increasing mental health care use prior to the diagnosis of PD. The aim of this study is to compare the level of mental health care use of PD patients with that of a matched control population, and to assess possible fluctuations in mental health care use in the years surrounding the diagnosis of PD. METHODS: Record linkage study comparing the number of mental health care contacts by PD patients with that of a matched control population. RESULTS: Mental health care use by PD patients already increased before the time of diagnosis of PD, and decreased again after diagnosis. The relative risk for mental health care use was increased from 3 years prior (RR 1.41; 95% CI 1.27-1.57) to 2 years after (RR 1.83; 95% CI 1.63-2.05) diagnosing PD. This increase was higher for women than for men, and higher for younger than older individuals. CONCLUSION: The early pathophysiology of PD is expressed in part as mental health problems, suggesting the possibility of early detection in particular demographic groups and a proactive approach to early intervention for comorbid psychopathology.

Ehrt U, Brønnick K, Leentjens AF, Larsen JP, Aarsland D. · Section of Geriatric Psychiatry, Stavanger University Hospital, Norway. · Int J Geriatr Psychiatry. · Pubmed #16477585 No free full text.

Abstract: OBJECTIVE: Depression is a common neuropsychiatric syndrome in Parkinson's disease (PD), and may be etiologically related to the neurochemical changes accompanying this disease. It is still unclear whether the disturbances of neurotransmitter activities lead to a specific profile of depressive symptoms, that is characteristic for PD and differs from that in depressed patients without PD. METHOD: We compared the individual depressive symptoms of 145 non-demented depressed patients with PD and 100 depressed patients without PD by comparing item scores on the Montgomery-Asberg Depression Rating Scale by way of MANCOVA. RESULTS: The severity of depression and the level of cognitive functioning in depressed PD patients were comparable with that of depressed control subjects. However, patients with PD showed significant less reported sadness, less anhedonia, less feelings of guilt and, slightly less loss of energy, but more concentration problems than depressed control subjects. CONCLUSION: The profile of depressive symptoms in PD differs from that in depressed subjects without PD. This finding is important for the conceptualisation and clinical diagnosis of depression in PD.

Visser M, Leentjens AF, Marinus J, Stiggelbout AM, van Hilten JJ. · Department of Neurology, Leiden University Medical Center, Leiden, and Deparment of Psychiatry, Maastricht University Hospital, The Netherlands. · Mov Disord. · Pubmed #16450355 No free full text.

Abstract: We evaluated the validity, reliability, and potential responsiveness of the Beck Depression Inventory (BDI) in patients with Parkinson's disease (PD). In part 1 of the study, 92 patients with PD underwent a structured clinical interview for DSM major depression and based on this patients were considered depressed (PD-D) or nondepressed (PD-ND). Subsequently, patients filled in the BDI. In part 2, a postal survey consisting the BDI was performed in 185 PD patients and 112 controls. Test-retest reliability was assessed in 60 PD patients. The factor analysis revealed a cognitive-affective and a somatic factor. Cronbachs alpha for the BDI was 0.88. Mean BDI indicated significant differences (P<0.001) between the PD and control group, between the PD-ND and PD-D group, and between PD-ND and control group. In part 1, the receiver operating characteristic curves showed that the area under the curve for the total BDI was 0.88. A cutoff was calculated for the BDI (14/15) that had the highest sum of sensitivity (0.71) and specificity (0.90). In part 2, the test-retest reliability for the BDI total score was 0.89 (intraclass correlation coefficient). The smallest real difference was 3.3 for the total BDI. The BDI is a valid, reliable, and potential responsive instrument to assess the severity of depression in PD. However, an adjusted cutoff is recommended.

Leentjens AF, Scholtissen B, Vreeling FW, Verhey FR. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Neuropsychopharmacology. · Pubmed #16205779 links to  free full text

Abstract: The serotonergic hypothesis for depression in Parkinson's disease (PD) states that the reduced cerebral serotonergic activity that occurs in PD constitutes a biological risk factor for depression. The aim of our study was to assess the serotonergic hypothesis of depression in PD patients using an experimental approach. In a double-blind, randomized order, placebo-controlled crossover design, the response on the Profile of Mood States (POMS) questionnaire to acute tryptophan depletion (ATD) was studied in 15 PD nondepressed patients and 15 control subjects, without a prior personal or family history of depression. PD patients had lower (worse) baseline scores on the sadness, fatigue and vigor subscales of the POMS, in both ATD and the placebo condition, but not on the tension and anger subscales. There was however neither a significance between group effect, nor significance within-group effect due to ATD. We could find no evidence of a specific serotonergic vulnerability of PD patients for depression. Therefore, our results do not support the serotonergic hypothesis for depression in PD.

Leentjens AF, Visser-Vandewalle V, Temel Y, Verhey FR. · Afd. Psychiatrie, Academisch Ziekenhuis, Postbus 5800, 6202 AZ Maastricht. · Ned Tijdschr Geneeskd. · Pubmed #15291423 No free full text.

Abstract: Three years after the implantation of electrodes in the subthalamic nucleus (STN) and the start of deep brain stimulation (DBS) for advanced Parkinson's disease, a 62-year-old man was admitted because of a stimulation-related manic state that did not respond to treatment with a mood stabiliser and that led to chaotic behaviour, megalomania, serious financial debts and mental incompetence. Although adjustment of the stimulation parameters resulted in a normophoric state with a return of insight and capacity to judge, this was only at the cost of a serious exacerbation of his motor symptoms that left the patient bedridden. There was no therapeutic margin between the two states. Ultimately, there seemed to be only two alternatives: to admit the patient to a nursing home because of serious invalidity, but mentally in good condition, or to admit the patient to a chronic psychiatric ward because of a manic state, but with acceptable motor capacity and ADL functions. Thorough ethical evaluation followed. When not being stimulated, the patient was considered competent to decide about his own treatment; in this condition the patient chose for the second option. In accordance with his own wishes he was therefore legally committed to a chronic ward in the regional psychiatric hospital. The current ethical views on mental competence do not consider the potential influence of modern methods of treatment such as STN-DBS on this capacity.

Leentjens AF, Van den Akker M, Metsemakers JF, Lousberg R, Verhey FR. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Mov Disord. · Pubmed #12671948 No free full text.

Abstract: Although case histories of depression preceding Parkinson's disease (PD) point to a possible pathophysiological relationship between these two disorders, there is as yet no epidemiological evidence to support this view. We compared the incidence of depression in patients later diagnosed with PD with that of a matched control population. Using data from an ongoing general practice-based register study, the lifetime incidence of depressive disorder was calculated for patients until their diagnosis of PD and compared with that of a matched control population from the same register. At the time of analysis, the register held information on 105416 people. At the time of their diagnosis of PD, 9.2% of the patients had a history of depression, compared with 4.0% of the control population (chi(2) = 22.388, df = 1, P < 0.001). The odds ratio for a history of depression for these patients was 2.4 (95% CI: 2.1-2.7). We concluded that the higher incidence of depression in patients who were later diagnosed with PD supports the hypothesis of there being a biological risk factor for depression in these patients.

Leentjens AF, Marinus J, Van Hilten JJ, Lousberg R, Verhey FR. · Deparment of Psychiatry, Maastricht University Hospital, The Netherlands. · J Neuropsychiatry Clin Neurosci. · Pubmed #12556575 links to  free full text

Abstract: This study assessed the sensitivity of individual depressive symptoms and their relative contribution to the diagnosis of depressive disorder in patients with Parkinson's disease. The Structured Clinical Interview for DSM-IV Depression and the Hamilton and Montgomery-Asberg depression rating scales (Ham-D, MADRS) were administered to 149 consecutive nondemented patients. The contribution of the individual items of these scales to the diagnosis of "depressive disorder" was calculated by discriminant analysis. The discriminant models based on the Ham-D and MADRS scores were both highly significant. Nonsomatic core symptoms of depression had the highest correlation coefficient. Somatic items had mostly low correlation coefficients, with the exception of reduced appetite and early morning wakening (late insomnia). Nonsomatic symptoms of depression appear to be the most important for distinguishing between depressed and nondepressed patients with Parkinson's disease, along with reduced appetite and early morning awakening.

Marinus J, Leentjens AF, Visser M, Stiggelbout AM, van Hilten JJ. · Department of Neurology, Leiden University Medical Center, The Netherlands. · Clin Neuropharmacol. · Pubmed #12469006 No free full text.

Abstract: The purpose of this study was to evaluate the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in patients with Parkinson's disease (PD) and to assess the prevalence of symptoms of anxiety and depression in this population. The HADS was sent to 205 patients with PD, together with three quality-of-life (QoL) instruments, i.e. the Parkinson's Disease Questionnaire (PDQ-39), the EQ-5D, and a visual analogue scale (VAS). Hospital Anxiety and Depression Scale scores were also compared with Hoehn-Yahr (H&Y) scores. Eighty-six percent of the patients returned the questionnaires. The quality of the data was good. Cronbach alpha for the HADS was 0.88. Test-retest reliability over 2 weeks was 0.84 for the sum score of the HADS (intraclass correlation coefficient) and ranged from 0.42-0.76 for individual items (weighted kappa). Factor analysis revealed two factors, accounting for 51.9% of the variance. One factor represented anxiety, the other depression. Correlations with PDQ-39, EQ-5D, VAS, and H&Y were 0.72, -0.59, -0.59, and 0.32, respectively (p values < 0.001). Depression scores accounted for 52% of the variance in QoL, whereas disease severity explained 24%. Using the cut-off values proposed by the developers indicated that possible and probable anxiety were present in 29.4% and 19.8% of the patients, respectively. Percentages for possible and probable depression were 21.5 and 16.9. The psychometric performance of the HADS in patients with PD is satisfactory. In addition, almost 50% of the patients displayed symptoms of anxiety, whereas nearly 40% showed signs of depression.

Leentjens AF, Lousberg R, Verhey FR. · Department of Psychiatry, Maastricht University Hospital, The Netherlands. · Acta Psychiatr Scand. · Pubmed #12197857 No free full text.

Abstract: OBJECTIVE: To assess whether general risk factors for depression are also markers of depression in patients with Parkinson's disease (PD) and to identify additional disease-specific markers. METHOD: A two-step logistic regression was performed on data from 161 consecutively referred PD patients, 40 of whom suffered from major depressive disorder. A first logistic model was created with five general risk factors for depression. Next, five potential disease-specific markers were added to see whether this would improve the model. RESULTS: The logistic model of general risk factors for depression also predicted depression in PD patients. A family history of depression was the most important marker. 'Right-sided onset' was the only disease-specific marker that improved the model. CONCLUSION: Established risk factors for depression in the general population are also markers of depression in PD. The importance of correcting for general risk factors for depression in the search for disease-specific risk factors is stressed.

Naarding P, Leentjens AF, van Kooten F, Verhey FR. · Department of Psychiatry, University Medical Center Nijmegen, The Netherlands. · J Neuropsychiatry Clin Neurosci. · Pubmed #12154158 links to  free full text

Abstract: To compare the psychometric properties of the Hamilton Rating Scale for Depression (Ham-D) in patients with stroke, Alzheimer's dementia (AD), and Parkinson's disease (PD), receiver operating characteristic curves were plotted for each group. The concurrent validity of the Ham-D with the DSM-IV criteria for major depressive disorder was high in each of these groups. However, optimal performance of the Ham-D requires the application of disease-specific cutoff scores for screening, diagnostic, and dichotomization purposes. These disease-specific cutoff scores were highest in PD, lower in AD, and lowest in stroke patients.

Schuurman AG, van den Akker M, Ensinck KT, Metsemakers JF, Knottnerus JA, Leentjens AF, Buntinx F. · Department of General Practice, Maastricht University, the Netherlands. · Neurology. · Pubmed #12034786 No free full text.

Abstract: BACKGROUND: Depression has been linked to the occurrence of a number of somatic diseases. There are no data for PD. OBJECTIVE: To determine if depression is associated with a subsequent risk for PD. METHODS: A retrospective cohort study design based in general practice was applied. All subjects diagnosed with depression between 1975 and 1990 were included and matched with subjects with the same birth year who were never diagnosed with depression. Follow-up ended at April 30, 2000. Hazard ratios (HR) and 95% CI were calculated using Cox proportional hazards models adjusted for age, sex, and socioeconomic status. Subgroups based on sex and age at diagnosis of depression were evaluated separately. RESULTS: Among the 1,358 depressed subjects, 19 developed PD, and among the 67,570 nondepressed subjects, 259 developed PD. The HR (95% CI) for depressed vs nondepressed subjects was 3.13 (1.95 to 5.01) in multivariable analysis. Associations in subgroups were comparable with the overall association. CONCLUSION: A strong positive association was found between depression and subsequent incidence of D.

Leentjens AF, Verhey FR, Luijckx GJ, Troost J. · Department of Psychiatry, Maastricht University Hospital, The Netherlands. · Mov Disord. · Pubmed #11104209 No free full text.

Abstract: PURPOSE: To evaluate the validity of the Beck Depression Inventory (BDI) as a screening and diagnostic scale for depression in Parkinson's disease (PD). PATIENTS AND METHODS: Fifty-three nondemented patients with PD were diagnosed according to a standardized protocol consisting of the depression module of the Structured Clinical Interview for DSM axis I disorders (SCID) and the BDI. A "receiver operating characteristics" (ROC) curve was obtained and the sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) were calculated for different cut-off points of the BDI. RESULTS: Maximum discrimination was obtained with a cut-off score of 13/14. High sensitivity and NPV were obtained with cut-off scores of 8/9 or lower; a high specificity and PPV were obtained with cut-off scores of 16/17 or higher. The area under the ROC curve was 85.67%. CONCLUSION: A single cut-off score on the BDI to distinguish nondepressed from depressed patients with PD is not feasible. If one accepts the low specificity, then the BDI can be used as a valid screening instrument for depression in PD with a cut-off of 8/9. With a cut-off score of 16/17, it can be used as a diagnostic scale, at the cost of a low sensitivity. The use of diagnostic criteria for depression remains necessary.

Leentjens AF, Verhey FR, Vreeling FW. · Afd. Psychiatrie, Academisch Ziekenhuis, Maastricht. · Ned Tijdschr Geneeskd. · Pubmed #11086491 No free full text.

Abstract: A 70-year-old female patient with Parkinson's disease was admitted to hospital with a medication-resistant depression. Electroconvulsion therapy was considered indicated, but it was decided to try treatment with bupropion chloride first. This resulted in a quick and complete remission of depressive symptoms, without any negative effects on motor symptoms. Bupropion has a unique mechanism of action: inhibition of the presynaptic reuptake of dopamine in addition to noradrenergic activity. Furthermore, it lacks the negative adverse effects on the extrapiramidal symptoms, that may be a problem if other antidepressants are used in the treatment. Bupropion is useful as an antidepressant in specific patient groups, notably patients with Parkinson's disease.

Leentjens AF, Verhey FR, Lousberg R, Spitsbergen H, Wilmink FW. · Department of Psychiatry, Maastricht University Hospital, The Netherlands. · Int J Geriatr Psychiatry. · Pubmed #10918346 No free full text.

Abstract: The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Asberg Depression Rating Scale (MADRS) against the DSM-IV diagnosis 'depressive disorder' was assessed in patients with Parkinson's disease (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the outpatient department of an academic hospital were diagnosed according to a standardised research protocol. This protocol consisted of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or absence of 'depressive disorder' according to the DSM-IV criteria, as well as the HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves) were obtained and the positive and negative predictive values (PPV, NPV) were calculated for different cut-off scores. Maximum discrimination between depressed and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD-17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and 14/15 for the MADRS, the high sensitivity and NPV make these scales good screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and 17/18 for the MADRS, the high specificity and PPV make these instruments good diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly better than that of the MADRS. This study shows that it is justified to use the HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize patient samples into depressed and non-depressed groups.