Roland Mergl

Identifying depression in primary care: a comparison of different methods in a prospective cohort study

Depressive disorders are a major health problem in primary care, and at least half of these disorders remain undetected.1 There are two recommended approaches to diagnosing depression in primary care: one is to perform routine screening, and the other is to evaluate patients only when the clinical presentation triggers the suspicion of depression. Our aim was to compare these two approaches, and to compare three different screening tools in order to evaluate which would be most appropriate for use in primary care. From among the many available screening tools, we selected three brief, self rating instruments: one disorder-specific (the depression module of the brief patient health questionnaire (B-PHQ, 9 items)),2 one broad based (the general health questionnaire (GHQ-12, 12 items)),3 and one that is less restricted to both issues (WHO-5 wellbeing index (WHO-5, 5 items)).4 Eighteen primary care facilities …

Treatment of depression with atypical features: A meta-analytic approach

The present meta-analysis addressed the empirical evidence regarding the treatment of major depression with atypical features. The superiority of monoamine oxidase inhibitors (MAOIs) compared with other antidepressants in the treatment of major depression with atypical features has been frequently reported. According to the CONSORT Statement, studies included in our meta-analysis had to meet several criteria, especially a double-blind, controlled condition and an operational diagnosis according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-III or DSM-IV criteria, respectively. Four databases for research-based evidence were used in a systematic review: Medline, Embase, Psyndex and PsycInfo. Only eight publications met inclusion/exclusion criteria, resulting in 11 comparisons. Our results contrast an effect size of 0.45 (95% confidence interval) for a comparison of MAOIs vs. placebo with an effect size of 0.02 (95% confidence interval: - 0.10-0.14) for a comparison of MAOIs vs. selective serotonin reuptake inhibitors. The effect size for MAOIs vs. tricyclic antidepressants was 0.27 (95% confidence interval: 0.16-0.42). MAOIs may be more effective for atypical major depressive disorder than tricyclic antidepressants. Most clinical research has been conducted on irreversible MAOIs. Additional studies testing more recently developed antidepressants (including reversible MAOIs) with an improved safety profile would be warranted. The available data are insufficient for a direct comparison between MAOIs and selective serotonin reuptake inhibitors.

Digitized analysis of handwriting and drawing movements in healthy subjects: methods, results and perspectives.

The diagnosis of movement disorders and the distinction between their possible generation by drug-treatment or illness can be done more objectively by using digitized analyses of hand movements. The aim of this study was to define this method, that is to identify its reliability and the influence of several covariables upon measurements, in healthy subjects. Simple writing and drawing tests were administered, using a digitizing tablet, transmitting signals to a computer for processing. The kinematic parameters identified in this way provided objective, reliable and valid measures for the dynamics and the degree of automation of hand movements. Analysis of the data showed that younger subjects write faster and with a higher degree of automation than older subjects. Other moderating variables, such as verbal intelligence and customary motor activity in everyday life (motoric practice) could be identified, whereas personality and gender were found to have little influence. There were no significant differences between left-handers and right-handers in hand movements. The movement parameters had a high test retest stability. The results of this study in healthy subjects indicate that age, verbal intelligence and motor practice should be considered when evaluating the effects of drug-treatment or psychiatric illness upon hand-movement in patients.

Inflammatory cytokines in general and central obesity and modulating effects of physical activity.

Context Chronic systemic inflammation in obesity originates from local immune responses in visceral adipose tissue. However, assessment of a broad range of inflammation-mediating cytokines and their relationship to physical activity and adipometrics has scarcely been reported to date. Objective To characterize the profile of a broad range of pro- and anti-inflammatory cytokines and the impact of physical activity and energy expenditure in individuals with general obesity, central obesity, and non-obese subjects. Design, Setting, and Participants A cross-sectional study comprising 117 obese patients (body mass index (BMI) ≥ 30) and 83 non-obese community-based volunteers. Main Outcomes Measures Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured. Physical activity and energy expenditure (MET) were assessed with actigraphy. Adipometrics comprised BMI, weight, abdominal-, waist- and hip-circumference, waist to hip ratio (WHR), and waist-to-height-ratio (WHtR). Results General obesity was associated with significantly elevated levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF-α, central obesity with significantly elevated IL-5, IL-10, IL-12, IL-13 and IFN-γ-levels. In participants with general obesity, levels of IL-4, IL-10 and IL-13 were significantly elevated in participants with low physical activity, even when controlled for BMI which was negatively associated with physical acitivity. Cytokines significantly correlated with adipometrics, particularly in obese participants. Conclusions Results confirm up-regulation of certain pro- and anti-inflammatory cytokines in obesity. In obese subjects, physical activity may lower levels and thus reduce pro-inflammatory effects of cytokines that may link obesity, insulin resistance and diabetes.

Early improvement is a predictor of treatment outcome in patients with mild major, minor or subsyndromal depression

BACKGROUND There is substantial evidence that early improvement (EI) under antidepressant treatment is a clinically useful predictor of later treatment outcome in patients with major depressive disorders. The aim of this study was to test whether EI can also be used as a predictor for treatment outcome in patients with mild major, minor or subsyndromal depression, i.e. patients, who are typically treated by general practitioners. METHODS Analyses were carried out using data from 223 patients of a 10-weeks randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy (CBT) in patients with mild major, minor or subsyndromal depression. EI was defined as a reduction of > or =20% on the 17-item Hamilton Rating Scale for Depression (HAMD-17) compared with baseline within the first 2 weeks of treatment. The predictive value of EI for stable response at week 8 and 10 (> or =50% HAMD-17 sum score reduction at weeks 8 and 10) and stable remission (HAMD-17 sum score < or =7 at weeks 8 and 10) was evaluated. RESULTS In both the sertraline- and CBT-treatment group, EI was a highly sensitive predictor for later stable response (76% and 82%, respectively) and stable remission (70% and 75%, respectively). In patients without EI, only a small proportion of sertraline or CBT-treated patients achieved stable response (20.9% and 5.9%, respectively) or stable remission (18.6% and 8.8%, respectively). Patients with EI were by far more likely to achieve stable response or stable remission than patients without as indicated by high odds ratios (95% confidence interval) of 8.1 (3.0-21.8) and 3.8 (1.4-10.1) for sertraline, and 11.1 (2.1-58.4) and 7.2 (1.7-30.8) for CBT-treated patients, respectively. LIMITATIONS Sample sizes were relatively low in different treatment groups. CONCLUSION The identification of early improvement might be useful in clinical decision making in the early course of treatment of patients with mild major, minor and subthreshold depression.

Kinematic Analysis of Handwriting Movements in Patients with Alzheimer's Disease, Mild Cognitive Impairment, Depression and Healthy Subjects

A variety of studies have demonstrated that motor disorders, parkinsonism and extrapyramidal motor symptoms (EPMS) are common in patients with Alzheimer’s disease (AD). Several studies have reported an association of EPMS with severity, progression and poor prognosis of AD. The majority of these studies used clinical assessments for the rating of EPMS. In this study, kinematic handwriting analysis was used to quantify differences in fine hand motor function in patients with probable AD and mild cognitive impairment (MCI, as an assumed initial stage of AD) compared to depressed patients and healthy controls. Both patients with MCI and patients with probable AD exhibited loss of fine motor performance. Movements of AD patients were significantly less regular than those of healthy controls.

Are Treatment Preferences Relevant in Response to Serotonergic Antidepressants and Cognitive-Behavioral Therapy in Depressed Primary Care Patients? Results from a Randomized Controlled Trial Including a Patients’ Choice Arm

Background: Little is known about the influence of depressed patients’ preferences and expectations about treatments upon treatment outcome. We investigated whether better clinical outcome in depressed primary care patients is associated with receiving their preferred treatment. Methods: Within a randomized placebo-controlled single-centre 10-week trial with 5 arms (sertraline; placebo; cognitive-behavioral group therapy, CBT-G; moderated self-help group control; treatment with sertraline or CBT-G according to patients’ choice), outcomes for 145 primary care patients with mild-to-moderate depressive disorders according to DSM-IV criteria were investigated. Preference for medication versus psychotherapy was assessed at screening using a single item. Post-baseline difference scores for the Hamilton Depression Rating Scale (HAMD-17) were used to assess treatment outcome (mixed-model repeated-measures regression analysis). Results: Depressed patients receiving their preferred treatment (n = 63), whether sertraline or CBT-G, responded significantly better than those who did not receive their preferred therapy (n = 54; p = 0.001). The difference in outcome between both groups was 8.0 points on the HAMD-17 for psychotherapy and 2.9 points on the HAMD-17 for treatment with antidepressants. Results were not explained by differences in depression severity or dropout rates. Conclusions: Patients’ relative preference for medication versus psychotherapy should be considered when offering a treatment because receiving the preferred treatment conveys an additional and clinically relevant benefit (HAMD-17: +2.9 points for drugs; +8.0 points for CBT-G) in outcome.

Auditory cortex and anterior cingulate cortex sources of the early evoked gamma-band response: Relationship to task difficulty and mental effort

High frequency oscillations in the 40 Hz (gamma-band)-range are involved in the synchronization of brain regions, e.g., in cognitive functions. It has been suggested that the auditory evoked gamma-band response (GBR) is affected by attention and apart from auditory cortex activity a frontal or anterior cingulate cortex (ACC) generator could be involved. It was the aim of the present study to address three questions: (1) is there a neural generator of the early evoked GBR in the dorsal (d)ACC? (2) Are there different activation patterns in the dACC and the auditory cortex areas in response to task difficulty? (3) Is it possible to detect an influence of early ACC-gamma-band activity (GBR timeframe) to later auditory information processing (N1 timeframe)? In the present EEG/ERP-study we have investigated 30 healthy subjects using six auditory reaction tasks with increasing difficulty and mental effort demands. In the MANOVA analysis we found a significant main effect of task difficulty on both the GBR amplitude (F=7.75; p<0.001) and the auditory evoked N1 potential (F=7.00; p<0.001) with higher amplitudes in the more difficult tasks. In the LORETA region of interest (ROI) analysis, this effect was only due to increased dACC-activity during the GBR-timeframe. For the ROI analysis during the N1 timeframe, in addition to a strong effect of task difficulty in the dACC a similar main effect was found in the auditory association area 22. These findings are in line with a top-down influence of dACC-activity to the auditory association area 22 during the early evoked GBR.

Influence of age and movement complexity on kinematic hand movement parameters in childhood and adolescence

Development of fine motor functions, especially drawing and handwriting, are crucial for performance in school, autonomy in everyday life and the general human development. A variety of neurological and psychiatric conditions in childhood and adolescence stunt the normal development of fine motor skills. We sought to define the normal development of the kinematic parameters of fine motor movement and determine the influence of gender, laterality of handedness and extracurricular training on fine motor skills.

Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.