Matthias R. Lemke

Depression and Parkinson's disease.

Abstract.Depression occurs in approximately 45% of all patients with Parkinson’s disease (PD), reduces quality of life independent of motor symptoms and seems to be underrated and undertreated. Characteristics of symptoms differ from major depression. Because of overlapping clinical symptoms, diagnosis is based on subjectively experienced anhedonia and feeling of emptiness. Available rating scales for major depression may not be adequate to correctly measure severity of depression in PD. Anxiety and depression may manifest as first symptoms of PD many years before motor symptoms. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the etiology of depression in PD. Tricyclic and newer, selective antidepressants including serotonin and noradrenaline reuptake inhibitors (SSRI, SNRI) appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to have a favorable side effect profile. Recent controlled studies show antidepressant effects of pramipexole in bipolar II depression. New dopamine agonists pramipexole and ropinirole appear to ameliorate depressive symptoms in PD in addition to effects on motor symptoms. There is a lack of appropriate rating scales and controlled studies regarding depression in PD.

Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease

Depression affects approximately 45% of all patients with Parkinsons disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinsons disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinsons disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinsons-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinsons disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.

Spatiotemporal gait patterns during over ground locomotion in major depression compared with healthy controls

Alterations of locomotion are frequent, observable features of patients suffering from depression and have been investigated in these patients by actigraphy, cinematography and ground reaction forces. However, spatiotemporal parameters and neurophysiological mechanisms of gait have not yet been studied in depth in depression. The relationship between spatial and temporal parameters may yield insight into the pathophysiology of altered movements in depression. Therefore, gait patterns were quantitatively assessed and analysed in depressed subjects (n=16) and compared to matched healthy controls. Spatiotemporal gait parameters were measured during over ground walking at self-selected walking speed on a walkway previously validated in healthy subjects and used for orthopaedic and neurological patients. Compared to controls, depressed patients showed significantly lower gait velocity (p<0.001), reduced stride length (p<0.005), double limb support (p<0.005) and cycle duration (p<0.005). There was a significant correlation between cadence and gait velocity in depressed patients (r=0.51, p<0.05), but not in healthy controls (r=0.11, p>0.05). In patients with major depression, reduced gait velocity was associated with stride hypometria and increased cycle duration. Velocity was associated with cadence in depressed patients but not in healthy controls. The results may indicate possible deficiencies in the motor control system in depression. These first results about alterations of spatiotemporal gait patterns in depression warrant further longitudinal and experimental studies.

Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders

BACKGROUND To assess criteria and to identify predictive factors for functional outcome. The criteria should cover all domains proposed by the Remission in Schizophrenia Working Group. METHOD PANSS ratings were used to evaluate the symptomatic treatment outcome of 262 inpatients with schizophrenia spectrum disorders within a naturalistic multicenter trial. Functional remission was defined as a GAF score >61 (Global Assessment of Functioning Scale), SOFAS score >61 (Social and Occupational Functioning Scale) and a SF-36 mental health subscore >40 (Medical Outcomes Study-Short Form Health Survey). Multivariate logistic regression and CART analyses were used to determine valid clinical and sociodemographic predictors. RESULTS In total, 52 patients (20%) fulfilled the criteria for functional remission, 125 patients (48%) achieved symptomatic resolution and when criteria for functional remission and symptomatic resolution were combined 33 patients (13%) achieved complete remission. Younger age, employment, a shorter duration of illness, a shorter length of current episode, less suicidality, and a lower PANSS negative and global subscore at admission were predictive of functional remission. The regression model showed a predictive value of more than 80%. CONCLUSIONS A significant association was found between functional remission and symptomatic resolution, indicating reasonable validity of the proposed definition for functional outcome. The revealed predictors for functional treatment outcome emphasize the need for psychosocial and vocational rehabilitation in schizophrenic patients.

Psychomotor retardation and anhedonia in depression.

Anhedonia, the inability to experience pleasure, and observed changes in psychomotor performance are frequent psychopathological phenomena in major depression with possible common neurobiological mechanisms. Interest, pleasure and reactivity to pleasurable stimuli contribute to movement generation and observable behaviour. Therefore the relationship between anhedonia and psychomotor retardation was studied in 48 depressed patients. Subjectively experienced anhedonia correlated with self‐rated but not with observer‐rated global severity of depression. There was a significant correlation between anhedonia and psychomotor retardation assessed with the Widlöcher Retardation Scale. The results suggest the existence of an empirical relationship between reduced ability to experience pleasure and observable psychomotor retardation in depression. Specific measures of psychomotor phenomena may provide further insights into the relationship between observable behaviour and self‐experienced symptoms in depression.

Predictors of Relapse in the Year After Hospital Discharge Among Patients With Schizophrenia

OBJECTIVE Relapse and its predictors were examined among patients with schizophrenia in the year after hospital discharge. METHODS The sample included 200 patients with schizophrenia participating in a German multicenter study. Relapse was defined as a worsening of psychopathological symptoms or rehospitalization in the year after hospital discharge. Predictors examined were variables related to course of illness and to response and remission at discharge. RESULTS Fifty-two percent of participants had a relapse. Patients whose symptoms were not in remission at discharge were more likely to have a relapse, as were those who had more severe symptoms and more side effects at discharge. Those who experienced a relapse were less likely to be taking a second-generation antipsychotic at discharge, less likely to have a positive attitude toward treatment adherence, and less likely to be employed. CONCLUSIONS The high rate of relapse among patients with schizophrenia highlights the need to improve current treatment strategies.

Motor activity and daily variation of symptom intensity in depressed patients

Spontaneous motor activity measured by actigraphy and subjectively experienced intensity of symptoms were investigated in 16 unipolar depressed inpatients with melancholic features. Patients felt significantly less active, awake, and more depressed in the morning compared to the evening. However, morning activity levels appeared significantly higher compared to evening levels. Diurnal variations of symptoms were reflected by actigraphically measured motor activity, which was negatively correlated with subjectively experienced symptom intensity. Increased motor activity may represent an observable, psychobiological, behavioral equivalent of self-experienced depressive symptoms in major depression with melancholic features.

Early improvement as a predictor of remission and response in schizophrenia: Results from a naturalistic study

OBJECTIVE To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement. METHODS Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge. RESULTS Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC=0.659) and response (AUC=0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%). CONCLUSION The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale

Schennach‐Wolff R, Obermeier M, Seemüller F, Jäger M, Messer T, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkötter J, Heuser I, Maier W, Lemke MR, Rüther E, Klingberg S, Gastpar M, Möller H‐J, Riedel M. Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

Evaluating Depressive Symptoms in Schizophrenia: A Psychometric Comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale

Background: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. Sampling and Methods: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. Results: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS subscores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. Conclusions: The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients.