Author
Astrid Zobel
Bio: Astrid Zobel is an academic researcher from University of Bonn. The author has contributed to research in topics: Escitalopram & Nortriptyline. The author has an hindex of 36, co-authored 63 publications receiving 4612 citations.
Papers
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TL;DR: The results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates, and genome-wide studies, if properly replicated, may be important steps in the elucidation of the genetic basis of pharmacological response.
Abstract: ObjectiveThe purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs. MethodHigh-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial. ResultsSingle nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between...
326 citations
TL;DR: The findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.
307 citations
TL;DR: Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates.
Abstract: Background
Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.
294 citations
TL;DR: The MADRS and the BDI can be recommended as complementary measures of depression severity and the three factor scores are proposed for external validation.
Abstract: BACKGROUND: A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales. METHOD: The 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores. RESULTS: The MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely 'observed mood and anxiety', 'cognitive' and 'neurovegetative', provided a more detailed description of depression severity. CONCLUSIONS: The MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.
245 citations
TL;DR: Most complaints listed as adverse reactions in people with depression were more common when they were medication-free rather than during their treatment with antidepressants, suggesting attention to specific adverse reactions may improve adherence to antidepressant treatment.
Abstract: Background
Adverse drug reactions are important determinants of non-adherence to antidepressant treatment, but their assessment is complicated by overlap with depressive symptoms and lack of reliable self-report measures.
Aims
To evaluate a simple self-report measure and describe adverse reactions to antidepressants in a large sample.
Method
The newly developed self-report Antidepressant Side-Effect Checklist and the psychiatrist-rated UKU Side Effect Rating Scale were repeatedly administered to 811 adult participants with depression in a part-randomised multicentre open-label study comparing escitalopram and nortriptyline.
Results
There was good agreement between self-report and psychiatrists’ ratings. Most complaints listed as adverse reactions in people with depression were more common when they were medication-free rather than during their treatment with antidepressants. Dry mouth (74%), constipation (33%) and weight gain (15%) were associated with nortriptyline treatment. Diarrhoea (9%), insomnia (36%) and yawning (16%) were more common during treatment with escitalopram. Problems with urination and drowsiness predicted discontinuation of nortriptyline. Diarrhoea and decreased appetite predicted discontinuation of escitalopram.
Conclusions
Adverse reactions to antidepressants can be reliably assessed by self-report. Attention to specific adverse reactions may improve adherence to antidepressant treatment.
216 citations
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TL;DR: Recent findings showing that microbiota are important in normal healthy brain function are reviewed, and ongoing and future animal and clinical studies aimed at understanding the microbiota-gut-brain axis may provide novel approaches for prevention and treatment of mental illness.
1,710 citations
TL;DR: There is growing evidence that neuroticism is a psychological trait of profound public health significance, a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use.
Abstract: The personality trait of neuroticism refers to relatively stable tendencies to respond with negative emotions to threat, frustration, or loss. Individuals in the population vary markedly on this trait, ranging from frequent and intense emotional reactions to minor challenges to little emotional reaction even in the face of significant difficulties. Although not widely appreciated, there is growing evidence that neuroticism is a psychological trait of profound public health significance. Neuroticism is a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use. Indeed, neuroticism apparently is a predictor of the quality and longevity of our lives. Achieving a full understanding of the nature and origins of neuroticism, and the mechanisms through which neuroticism is linked to mental and physical disorders, should be a top priority for research. Knowing why neuroticism predicts such a wide variety of seemingly diverse outcomes should lead to improved understanding of commonalities among those outcomes and improved strategies for preventing them.
1,412 citations
TL;DR: It is demonstrated that major depressive disorder is reliably associated with impaired performance on neuropsychological measures of EF, and the results are consistent with the theory that MDD is associated with broad impairment in multiple aspects of EF.
Abstract: Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have found significant deficits associated with MDD on neuropsychological measures of EF, others have not, potentially due to low statistical power, task impurity, and diverse patient samples, and there have been no recent, comprehensive, meta-analyses investigating EF in patients with MDD. The current meta-analysis uses random-effects models to synthesize 113 previous research studies that compared participants with MDD to healthy control participants on at least one neuropsychological measure of EF. Results of the meta-analysis demonstrate that MDD is reliably associated with impaired performance on neuropsychological measures of EF, with effect sizes ranging from 0.32 to 0.97. Although patients with MDD also have slower processing speed, motor slowing alone cannot account for these results. In addition, some evidence suggests that deficits on neuropsychological measures of EF are greater in patients with more severe current depression symptoms, and those taking psychotropic medications, whereas evidence for effects of age was weaker. The results are consistent with the theory that MDD is associated with broad impairment in multiple aspects of EF. Implications for treatment of MDD and theories of EF are discussed. Future research is needed to establish the specificity and causal link between MDD and EF impairments.
1,243 citations
TL;DR: Research is reviewed about variation in the promoter region of the serotonin transporter gene (SLC6A4) and its contribution to stress sensitivity and the contribution of GxE research to the public understanding of genetic science.
Abstract: Evidence of marked variability in response among people exposed to the same environmental risk implies that individual differences in genetic susceptibility might be at work. The study of such Gene-by-Environment (GxE) interactions has gained momentum. In this article, the authors review research about one of the most extensive areas of inquiry: variation in the promoter region of the serotonin transporter gene (SLC6A4; also known as 5-HTT) and its contribution to stress sensitivity. Research in this area has both advanced basic science and generated broader lessons for studying complex diseases and traits. The authors evaluate four lines of evidence about the 5-HTT stress-sensitivity hypothesis: 1) observational studies about the serotonin transporter linked polymorphic region (5-HTTLPR), stress sensitivity, and depression in humans; 2) experimental neuroscience studies about the 5-HTTLPR and biological phenotypes relevant to the human stress response; 3) studies of 5-HTT variation and stress sen...
1,200 citations
TL;DR: A meta-analysis of 16 epidemiological studies suggested that childhood maltreatment was associated with an elevated risk of developing recurrent and persistent depressive episodes and with lack of response or remission during treatment for depression.
Abstract: Objectives:Evidence suggests that childhood maltreatment may negatively affect not only the lifetime risk of depression but also clinically relevant measures of depression, such as course of illness and treatment outcome. The authors conducted the first meta-analysis to examine the relationship between childhood maltreatment and these clinically relevant measures of depression. Method:The authors conducted searches in MEDLINE, PsycINFO, and Embase for articles examining the association of childhood maltreatment with course of illness (i.e., recurrence or persistence) and with treatment outcome in depression that appeared in the literature before December 31, 2010. Recurrence was defined in terms of number of depressive episodes. Persistence was defined in terms of duration of current depressive episode. Treatment outcome was defined in terms of either a response (a 50% reduction in depression severity rating from baseline) or remission (a decrease in depression severity below a predefined clinical signifi...
1,110 citations