Measuring motor activity in major depression: the association between the Hamilton Depression Rating Scale and actigraphy

Despite the use of actigraphy in depression research, the association of depression ratings and quantitative motor activity remains controversial. In addition, the impact of recurring episodes on motor activity is uncertain. In 76 medicated inpatients with major depression (27 with a first episode, 49 with recurrent episodes), continuous wrist actigraphy for 24h and scores on the Hamilton Depression Rating Scale (HAMD) were obtained. In addition, 10 subjects of the sample wore the actigraph over a period of 5 days, in order to assess the reliability of a 1-day measurement. Activity levels were stable over 5 consecutive days. Actigraphic parameters did not differ between patients with a first or a recurrent episode, and quantitative motor activity failed to correlate with the HAMD total score. However, of the motor-related single items of the HAMD, the item activities was associated with motor activity parameters, while the items agitation and retardation were not. Actigraphy is consistent with clinical observation for the item activities. Expert raters may not correctly rate the motor aspects of retardation and agitation in major depression.

German Validation of the Conners Adult ADHD Rating Scale-Self-Report: Confirmation of Factor Structure in a Large Sample of Participants With ADHD

Objective: The Conners Adult ADHD Rating Scales (CAARS) assess symptoms specific to adults that are frequently used and have been translated into German. The current study tests the factor structure of the CAARS in a large sample of German adults with ADHD and compares the means of the CAARS subscales with those of healthy German controls. Method: CAARS were completed by 466 participants with ADHD and 851 healthy control participants. Confirmatory factor analysis was used to establish model fit with the American original. Comparisons between participants with ADHD and healthy controls and influences of gender, age, and degree of education were analyzed. Results: Confirmatory factor analysis showed a very good fit with the model for the American original. Differences between ADHD participants and healthy controls on all Conners Adult ADHD Rating Scales-Self-Report (CAARS-S) subscales were substantial and significant. Conclusion: The factor structure of the original American model was successfully replicated in this sample of adult German ADHD participants. (J. of Att. Dis. 2012; XX(X) 1-XX).

Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients.

Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.

Measuring depression with a well-being index: Further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression

BACKGROUND: In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS: The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD: Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS: In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION: Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.

International validation of a behavioral scale in Parkinson's disease without dementia.

The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n = 260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ = 0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ = 0.56); apathy with the Lille Apathy Rating Scale (ρ = 0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia. © 2015 International Parkinson and Movement Disorder Society.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study is to investigate FAA and its correlation with resting – state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant for reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left – lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients) and in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right – lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.

RATIONALE: Thyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. OBJECTIVES: This study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. METHODS: This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.

Der WHO Wellbeing Index (WHO-5) als Depressivitätsmaß

Der WHO-5 erfasst mit fünf Items psychisches Wohlbefinden, er dient auch als Screeninginstrument zur Erfassung depressiver Symptomatik. Wenige Studien untersuchten diesen Validitätsaspekt jedoch im klinischen Kontext. Ziel der vorliegenden Studie war es, die Messinvarianz des WHO-5 zwischen depressiven und nicht-depressiven Stichproben sowie Art und Spezifität des Zusammenhangs mit Skalen zur Erfassung der Depressionsschwere zu überprüfen. Insgesamt 414 Personen füllten den WHO-5 und das BDI-II aus. Aktuell erfüllten 207 Personen die DSM-IV-Kriterien einer Major Depression (SKID-I). Eine Teilstichprobe erhielt zusätzlich das Beck-Anxiety-Inventory (BAI) und wurde auf der Hamilton-Depression-Rating-Scale (HAM-D) und der Hamilton- Anxiety-Rating-Scale (HAM-A) durch trainierte Rater eingeschätzt. Der WHO-5 wies hohe Messinvarianz bezüglich des Vorliegens/Nichtvorliegens einer Major Depression auf. Er zeigte hohe negative Zusammenhänge mit selbst- und fremdeingeschätzter Depressivität (BDI-II, HAM-D), insbesondere bei milderer und moderater Symptomschwere und auch nach Kontrolle gleichzeitig bestehender Angstsymptomatik. Diese Ergebnisse unterstützen die Verwendung des WHO-5 als Depressionsmaß, zumindest im Bereich milder und mittlerer Depressionsschwere.

Effects of subthalamic nucleus stimulation on cognition and mood in Parkinson’s disease (PD)

Objective: To assess the neuropsychological outcome as a safety measure and quality control in patients with subthalamic nucleus (STN) stimulation for PD. Background: Deep brain stimulation (DBS) is considered a relatively safe treatment used in patients with movement disorders. However, neuropsychological alterations have been reported in patients with STN DBS for PD. Cognition and mood are important determinants of quality of life in PD patients and must be assessed for safety control. Methods: Seventeen consecutive patients (8 women) who underwent STN DBS for PD have been assessed before and 4 months after surgery. Besides motor symptoms (UPDRS-III), mood (Beck Depression Inventory, Hamilton Depression Rating Scale) and neuropsychological aspects, mainly executive functions, have been assessed (mini mental state examination, semantic and phonematic verbal fluency, go-no go test, stroop test, trail making test, tests of alertness and attention, digit span, wordlist learning, praxia, Boston naming test, figure drawing, visual perception). Paired t-tests were used for comparisons before and after surgery. Results: Patients were 61.6±7.8 years old at baseline assessment. All surgeries were performed without major adverse events. Motor symptoms ‘‘on’’ medication remained stable whereas they improved in the ‘‘off’’ condition (p<0.001). Mood was not depressed before surgery and remained unchanged at follow-up. All neuropsychological assessment outcome measures remained stable at follow-up with the exception of semantic verbal fluency and wordlist learning. Semantic verbal fluency decreased by 21±16% (p<0.001) and there was a trend to worse phonematic verbal fluency after surgery (p=0.06). Recall of a list of 10 words was worse after surgery only for the third attempt of recall (13%, p<0.005). Conclusions: Verbal fluency decreased in our patients after STN DBS, as previously reported. The procedure was otherwise safe and did not lead to deterioration of mood.

Association between symptoms and quality of life in patients with schizophrenia: a pooled analysis of changes over time

Quality of life is an important outcome in the treatment of patients with schizophrenia. It has been suggested that patients' quality of life ratings (referred to as subjective quality of life, SQOL) might be too heavily influenced by symptomatology to be a valid independent outcome criterion. There has been only limited evidence on the association of symptom change and changes in SQOL over time. This study aimed to examine the association between changes in symptoms and in SQOL among patients with schizophrenia. A pooled data set was obtained from eight longitudinal studies that had used the Brief Psychiatric Rating Scale (BPRS) for measuring psychiatric symptoms and either the Lancashire Quality of Life Profile or the Manchester Short Assessment of Quality of Life for assessing SQOL. The sample comprised 886 patients with schizophrenia. After controlling for heterogeneity of findings across studies using linear mixed models, a reduction in psychiatric symptoms was associated with improvements in SQOL scores. In univariate analyses, changes in all BPRS subscales were associated with changes in SQOL scores. In a multivariate model, only associations between changes in the BPRS depression/anxiety and hostility subscales and changes in SQOL remained significant, with 5% and 0.5% of the variance in SQOL changes being attributable to changes in depression/anxiety and hostility respectively. All BPRS subscales together explained 8.5% of variance. The findings indicate that SQOL changes are influenced by symptom change, in particular in depression/anxiety. The level of influence is limited and may not compromise using SQOL as an independent outcome measure.

Disagreements in meta-analyses using outcomes measured on continuous or rating scales: observer agreement study

OBJECTIVE: To study the inter-observer variation related to extraction of continuous and numerical rating scale data from trial reports for use in meta-analyses. DESIGN: Observer agreement study. DATA SOURCES: A random sample of 10 Cochrane reviews that presented a result as a standardised mean difference (SMD), the protocols for the reviews and the trial reports (n=45) were retrieved. DATA EXTRACTION: Five experienced methodologists and five PhD students independently extracted data from the trial reports for calculation of the first SMD result in each review. The observers did not have access to the reviews but to the protocols, where the relevant outcome was highlighted. The agreement was analysed at both trial and meta-analysis level, pairing the observers in all possible ways (45 pairs, yielding 2025 pairs of trials and 450 pairs of meta-analyses). Agreement was defined as SMDs that differed less than 0.1 in their point estimates or confidence intervals. RESULTS: The agreement was 53% at trial level and 31% at meta-analysis level. Including all pairs, the median disagreement was SMD=0.22 (interquartile range 0.07-0.61). The experts agreed somewhat more than the PhD students at trial level (61% v 46%), but not at meta-analysis level. Important reasons for disagreement were differences in selection of time points, scales, control groups, and type of calculations; whether to include a trial in the meta-analysis; and data extraction errors made by the observers. In 14 out of the 100 SMDs calculated at the meta-analysis level, individual observers reached different conclusions than the originally published review. CONCLUSIONS: Disagreements were common and often larger than the effect of commonly used treatments. Meta-analyses using SMDs are prone to observer variation and should be interpreted with caution. The reliability of meta-analyses might be improved by having more detailed review protocols, more than one observer, and statistical expertise.

Patient-reported outcomes in meta-analyses - part 2: methods for improving interpretability for decision-makers

Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients, clinicians and policy-makers facing challenging health care decisions. Based on emerging methods, guidance on improving the interpretability of meta-analysis of patient-reported outcomes, typically continuous in nature, is likely to enhance decision-making. The objective of this paper is to summarize approaches to enhancing the interpretability of pooled estimates of PROs in meta-analyses. When differences in PROs between groups are statistically significant, decision-makers must be able to interpret the magnitude of effect. This is challenging when, as is often the case, clinical trial investigators use different measurement instruments for the same construct within and between individual randomized trials. For such cases, in addition to pooling results as a standardized mean difference, we recommend that systematic review authors use other methods to present results such as relative (relative risk, odds ratio) or absolute (risk difference) dichotomized treatment effects, complimented by presentation in either: natural units (e.g. overall depression reduced by 2.4 points when measured on a 50-point Hamilton Rating Scale for Depression); minimal important difference units (e.g. where 1.0 unit represents the smallest difference in depression that patients, on average, perceive as important the depression score was 0.38 (95%CI 0.30 to 0.47) units less than the control group); or a ratio of means (e.g. where the mean in the treatment group is divided by the mean in the control group, the ratio of means is 1.27, representing a 27%relative reduction in the mean depression score).

Myocardial Infarction - Stress PRevention INTervention (MI-SPRINT) to reduce the incidence of posttraumatic stress after acute myocardial infarction through trauma-focused psychological counseling: study protocol for a randomized controlled trial

BACKGROUND Posttraumatic Stress Disorder (PTSD) may occur in patients after exposure to a life-threatening illness. About one out of six patients develop clinically relevant levels of PTSD symptoms after acute myocardial infarction (MI). Symptoms of PTSD are associated with impaired quality of life and increase the risk of recurrent cardiovascular events. The main hypothesis of the MI-SPRINT study is that trauma-focused psychological counseling is more effective than non-trauma focused counseling in preventing posttraumatic stress after acute MI. METHODS/DESIGN The study is a single-center, randomized controlled psychological trial with two active intervention arms. The sample consists of 426 patients aged 18 years or older who are at 'high risk' to develop clinically relevant posttraumatic stress symptoms. 'High risk' patients are identified with three single-item questions with a numeric rating scale (0 to 10) asking about 'pain during MI', 'fear of dying until admission' and/or 'worrying and feeling helpless when being told about having MI'. Exclusion criteria are emergency heart surgery, severe comorbidities, current severe depression, disorientation, cognitive impairment and suicidal ideation. Patients will be randomly allocated to a single 45-minute counseling session targeting either specific MI-triggered traumatic reactions (that is, the verum intervention) or the general role of psychosocial stress in coronary heart disease (that is, the control intervention). The session will take place in the coronary care unit within 48 hours, by the bedside, after patients have reached stable circulatory conditions. Each patient will additionally receive an illustrated information booklet as study material. Sociodemographic factors, psychosocial and medical data, and cardiometabolic risk factors will be assessed during hospitalization. The primary outcome is the interviewer-rated posttraumatic stress level at three-month follow-up, which is hypothesized to be at least 20% lower in the verum group than in the control group using the t-test. Secondary outcomes are posttraumatic stress levels at 12-month follow-up, and psychosocial functioning and cardiometabolic risk factors at both follow-up assessments. DISCUSSION If the verum intervention proves to be effective, the study will be the first to show that a brief trauma-focused psychological intervention delivered within a somatic health care setting can reduce the incidence of posttraumatic stress in acute MI patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01781247.

Factors predicting protracted improvement after pallidal DBS for primary dystonia: the role of age and disease duration

In many patients, optimal results after pallidal deep brain stimulation (DBS) for primary dystonia may appear over several months, possibly beyond 1 year after implant. In order to elucidate the factors predicting such protracted clinical effect, we retrospectively reviewed the clinical records of 44 patients with primary dystonia and bilateral pallidal DBS implants. Patients with fixed skeletal deformities, as well as those with a history of prior ablative procedures, were excluded. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores at baseline, 1 and 3 years after DBS were used to evaluate clinical outcome. All subjects showed a significant improvement after DBS implants (mean BFMDRS improvement of 74.9% at 1 year and 82.6% at 3 years). Disease duration (DD, median 15 years, range 2-42) and age at surgery (AS, median 31 years, range 10-59) showed a significant negative correlation with DBS outcome at 1 and 3 years. A partition analysis, using DD and AS, clustered subjects into three groups: (1) younger subjects with shorter DD (n = 19, AS < 27, DD ? 17); (2) older subjects with shorter DD (n = 8, DD ? 17, AS ? 27); (3) older subjects with longer DD (n = 17, DD > 17, AS ? 27). Younger patients with short DD benefitted more and faster than older patients, who however continued to improve 10% on average 1 year after DBS implants. Our data suggest that subjects with short DD may expect to achieve a better general outcome than those with longer DD and that AS may influence the time necessary to achieve maximal clinical response.

Validity evidence and reliability of a Simulated Patient Feedback Instrument

In the training of healthcare professionals, one of the advantages of communication training with simulated patients (SPs) is the SP's ability to provide direct feedback to students after a simulated clinical encounter. The quality of SP feedback must be monitored, especially because it is well known that feedback can have a profound effect on student performance. Due to the current lack of valid and reliable instruments to assess the quality of SP feedback, our study examined the validity and reliability of one potential instrument, the 'modified Quality of Simulated Patient Feedback Form' (mQSF). Methods Content validity of the mQSF was assessed by inviting experts in the area of simulated clinical encounters to rate the importance of the mQSF items. Moreover, generalizability theory was used to examine the reliability of the mQSF. Our data came from videotapes of clinical encounters between six simulated patients and six students and the ensuing feedback from the SPs to the students. Ten faculty members judged the SP feedback according to the items on the mQSF. Three weeks later, this procedure was repeated with the same faculty members and recordings. Results All but two items of the mQSF received importance ratings of > 2.5 on a four-point rating scale. A generalizability coefficient of 0.77 was established with two judges observing one encounter. Conclusions The findings for content validity and reliability with two judges suggest that the mQSF is a valid and reliable instrument to assess the quality of feedback provided by simulated patients.