Rolf R Engel

Ludwig-Maximilians-University of Munich, München, Bavaria, Germany

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Publications (164)801.74 Total impact

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    ABSTRACT: Shame and guilt can be described as 'self-conscious emotions' and are an essential part of the psychopathology in obsessive-compulsive disorder (OCD). Our primary aim was to explore whether individuals with OCD are processing shame and guilt differently from healthy individuals (N = 20 in both groups; 50% female; age: 20-40 years) on the behavioural and neurobiological level. For the experimental task, participants were scanned with functional magnetic resonance tomography (functional magnetic resonance imaging, 3 T) while imagining neutral, shame inducing and guilt inducing scenarios. In addition to clinical questionnaires, participants were asked to complete questionnaires measuring shame and guilt. The functional data indicate an increased activity in OCD patients in the shame condition in the limbic, temporal and sub-lobar (hypothalamus) areas, in the guilt condition inter alia in frontal, limbic and temporal areas. In summary we found activity in OCD patients in neural networks which are responsible for stimulus filtering, emotion regulation, impulse control and memory. The results from our study may contribute to a better understanding of the origins and maintenance of OCD in association with the pathological processing of shame and guilt on different functional levels. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Psychiatric Research 05/2015; 68. DOI:10.1016/j.jpsychires.2015.05.001 · 3.96 Impact Factor
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    ABSTRACT: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany and Switzerland), the "Arzneimittelsicherheit in der Psychiatrie" (AMSP), which assesses severe ADRs occurring in clinical routine situations. Of 169,278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (MAOIs) (0.27%), TCAs (0.15%) and serotonin noradrenaline reuptake inhibitors (SNRIs) (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD (NaSSA) mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia and in some rare cases heart failure. Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 10/2014; 18(4). DOI:10.1093/ijnp/pyu080 · 4.01 Impact Factor
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    ABSTRACT: The Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) are rating scales commonly used to assess the level of functioning in patients with schizophrenia. To understand the correspondence of scores between GAF and SOFAS, and what they mean from a clinical point of view, we examined the linkage of (a) GAF with SOFAS total scores, (b) GAF with Clinical Global Impressions Scale (CGI) and Positive and Negative Syndrome Scale (PANSS), and (c) SOFAS with CGI and PANSS. We used the equipercentile linking method to identify corresponding scores of simultaneous GAF, SOFAS, PANSS and CGI ratings in 1208 patients from a naturalistic European cohort study. Data were collected at baseline and at months 6, 12, 18 and 24. GAF and SOFAS total scores were found to be practically exchangeable. Both scales had strong negative correlations with CGI and PANSS; the linkage also suggested the presence of slight impairment in functioning even when patients are free from symptoms. These findings are important for the comparison of scores when different rating scales are used. We present a detailed conversion table in an online supplement.
    European Neuropsychopharmacology 08/2014; 24(11). DOI:10.1016/j.euroneuro.2014.08.009 · 4.37 Impact Factor
  • Magdolna Tardy · Markus Dold · Rolf R Engel · Stefan Leucht
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    ABSTRACT: Flupenthixol was first made available in the UK in 1965 and it has been used to treat schizophrenia for nearly five decades. It is available both as a tablet and a long-acting injection. Having been investigated in numerous studies, flupenthixol was found to be effective and well tolerated by people with schizophrenia. The main side effects are shaking, restlessness or the inability to sit still, a dry mouth and some weight gain. Although this drug has been available for decades, few systematic reviews exist on flupenthixol. The effects of this drug in helping people cope with the symptoms of schizophrenia are not currently measured, quantified and known. The review could include only one small study, which was limited and 13 years old. The number as well as the quality of the study was low; for the main outcomes of interest the authors could not rate the quality of evidence at all, as the study did not report on the outcomes of interest for the 'Summary of findings' table. Flupenthixol was compared with chlorpromazine. There was no clear difference in efficacy, nor was there clear information on: increasing their use of services; people’s satisfaction with treatment; quality of life; or costs and cost effectiveness. Flupenthixol is widely available and inexpensive. It is perhaps understandable that it remains one of many drugs used for treating people with serious mental illnesses. This is because the use of flupenthixol is based more on clinical experience, and the decisions of psychiatrists are based on large scale research studies and evidence-based information. The effectiveness and benefits of flupenthixol over chlorpromazine remain largely unknown and incomplete. Large randomised trials could be helpful in increasing knowledge about this drug. This plain language summary has been written by Benjamin Gray, Service User Expert, Rethink Mental Illness.
    Cochrane database of systematic reviews (Online) 07/2014; 7(7):CD009396. DOI:10.1002/14651858.CD009396.pub2 · 6.03 Impact Factor
  • C Corves · R R Engel · J Davis · S Leucht
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    ABSTRACT: The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. We reanalyzed the original data from five different randomized drug trials comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing 427 paranoid and 296 disorganized patients with schizophrenia. Both the disorganized and the paranoid group showed a substantial improvement of the BPRS total score within the first 4 weeks. In the paranoid group, mean (±SD) BPRS reduction was 16.9 (±14.6) (t = 24.06, df = 426, P < 0.001) and in the disorganized group 17.0 (±15.9) (t = 18.49, df = 295, P < 0.001). An analysis of covariance (ancova) controlling for BPRS at baseline and the influence of different trial protocols showed significant differences between diagnostic groups (F = 13.47, df = 1, P < 0.001), Cohen's D 0.31 (CI = 0.16-0.46). Paranoid patients improved by 4.8 BPRS points more than disorganized patients (adjusted means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for the disorganized group. We conclude that amisulpride is effective in disorganized as well as in paranoid schizophrenia, but that symptom reduction in the disorganized subtype is less pronounced.
    Acta Psychiatrica Scandinavica 12/2013; 130(1). DOI:10.1111/acps.12231 · 5.61 Impact Factor
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    ABSTRACT: Missing outcome data is a major threat in meta-analytical studies of schizophrenia. Most clinical trials in psychiatry report only continuous outcome measures and express the effect of an intervention as a difference of means. However, these results are difficult to interpret for clinicians. Converting continuous data to binary response rates is one possible solution to the problem. Based on means and standard deviations for a continuous outcome, we examined the performance of an imputation method to define a dichotomous outcome using original individual patients' data from 16 randomized trials (6276 participants) comparing antipsychotic drugs in schizophrenia. We concluded that the imputed values re-captured in a reasonable degree the observed values providing a simple and practical alternative methodological choice for imputation of missing binary data in schizophrenia trials; nevertheless, the imputation method tended to introduce biases, especially for extreme risks and large treatment differences.
    Schizophrenia Research 11/2013; 151(1-3). DOI:10.1016/j.schres.2013.10.029 · 3.92 Impact Factor
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    ABSTRACT: There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed-the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk.
    Psychopharmacology 09/2013; 230(2). DOI:10.1007/s00213-013-3281-8 · 3.88 Impact Factor
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    ABSTRACT: Studies that compare neuropsychological functioning in inpatients with mood disorder or schizophrenia come to heterogeneous results. This study aims at investigating the question whether there are different neuropsychological test profiles in stabilised post-acute inpatients with affective disorders or schizophrenia. We were interested in evaluating impairment in specific areas of cognitive functioning in patients with schizophrenia or depression. In clinical reality, patients with depression and schizophrenia are often treated together with little attention to their specific needs. 74 patients with major depression and 38 patients with schizophrenia were assessed in a comprehensive neuropsychological battery. All patients were in a post-acute stage of their illness, i.e. remission of acute symptoms. In spite of a comparable mean score of psychopathological symptoms in the Brief Psychiatric Rating Scale-Expanded (BPRS-E) as well as in the Global Assessment Functioning Scale (GAF), patients with depressive disorder showed significantly better results in verbal and visual short-term memory, verbal fluency, visual-motor coordination, information processing in visual-verbal functioning and selective attention compared to patients with schizophrenia. No significant differences between both samples were found in practical reasoning, general verbal abstraction, spatial-figural functioning, speed of cognitive processing. These results show that there are differences in scores in psychopathology (BPRS-E, GAF) in patients with affective disorders or schizophrenia and different neuropsychological test profiles in the post-acute stage of their illness.
    BMC Psychiatry 08/2013; 13(1):203. DOI:10.1186/1471-244X-13-203 · 2.21 Impact Factor
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    ABSTRACT: This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.
    European Archives of Psychiatry and Clinical Neuroscience 07/2013; 264(2). DOI:10.1007/s00406-013-0419-y · 3.53 Impact Factor
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    ABSTRACT: The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from -0·09 for the best drug (haloperidol) to -0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to -1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to -0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. None.
    The Lancet 06/2013; 382(9896). DOI:10.1016/S0140-6736(13)60733-3 · 45.22 Impact Factor
  • S Leucht · P Rothe · J.M. Davis · R.R. Engel
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    ABSTRACT: The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) are the most frequently used scales to rate the symptoms of schizophrenia. There are many situations in which it is important to know what a given total score or a percent reduction from baseline score of one scale means in terms of the other scale. We used the equipercentile linking method to identify corresponding scores of simultaneous BPRS and PANSS ratings in 3767 patients from antipsychotic drug trials. Data were collected at baseline and at weeks 1, 2, 4 and 6. BPRS total scores of 18, 30, 40 and 50 roughly corresponded to PANSS total scores of 31, 55, 73 and 90, respectively. An absolute BPRS improvement of 10, 20, 30, 40 points corresponded to a PANSS improvement of 15, 32, 50, and 67. A percentage improvement of the BPRS total score from baseline of 19%, 30%, 40% and 50% roughly corresponded to percentage PANSS improvement of 16%, 25%, 35%, and 44%. Thus a given PANSS percent improvement was always lower than the corresponding BPRS percent improvement, on the average by 4-5%. A reason may be the higher number of items used in the PANSS. These results are important for the comparison of trials that used these rating scales. We present a detailed conversion table in an online supplement.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 02/2013; 23(8). DOI:10.1016/j.euroneuro.2012.11.004 · 4.37 Impact Factor
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    ABSTRACT: Little is known about the clinical relevance of the Hamilton Rating Scale for Depression (HAMD-17) total scores. It is unclear how total scores translate into clinical severity, or what commonly used measures for response (reduction from baseline of ≥50% in the total score) and remission (total HAMD-17 score ≤7) mean from a clinical perspective. We therefore compared: (a) the percentage and absolute change in the HAMD-17 total scores with Clinical Global Impression-Improvement (CGI-I); (b) the absolute and percentage change in the HAMD-17 total scores with Clinical Global Impression-Severity (CGI-S) absolute change; and (c) the percentage and absolute change in the HAMD-17 total scores with CGI-I in the subgroups of patients with≤median and>median HAMD-17 total scores at baseline. The method used was equipercentile linking of HAMD-17 and CGI ratings from 43 drug trials in patients with Major Depressive Disorder (MDD) (n=7131). Our results confirm the validity of the commonly used measures for remission and response in MDD trials: a CGI-I score of 2 ('much improved') corresponded to a reduction from baseline of >50% and <60%, and a CGI-I score of 1 ('very much improved') to a reduction of >75% and <85%. The CGI-S score of 1 ('normal., not at all ill') corresponded to the HAMD-17 total score of <5 and the CGI-S score of 2 ('borderline mentally ill') to the score between 6 and 8. An effect of baseline illness severity was observed.
    Journal of Affective Disorders 01/2013; 148(2). DOI:10.1016/j.jad.2012.12.001 · 3.38 Impact Factor
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    ABSTRACT: In this study, a functional magnetic resonance imaging paradigm originally employed by Takahashi et al. (2004) was adapted to look for emotion-specific differences in functional brain activity within a healthy German sample (N=14), using shame- and guilt-related stimuli and neutral stimuli.Activations were found for both of these emotions in the temporal lobe (shame condition: Anterior cingulate cortex, parahippocampal gyrus; guilt: Fusiform gyrus, middle temporal gyrus). Specific activations were found for shame in the frontal lobe (medial and inferior frontal gyrus), and for guilt in the amygdala and insula. This is consistent with Takahashi et al.'s (2004) results obtained for a Japanese sample (using Japanese stimuli), which showed activations in the fusiform gyrus, hippocampus, middle occipital gyrus and parahippocampal gyrus.During the imagination of shame, frontal and temporal areas (e.g. middle frontal gyrus and parahippocampal gyrus) were responsive regardless of gender. In the guilt condition, women only activate temporal regions, whereas men showed additional frontal and occipital activation as well as a responsive amygdala.The results suggest that shame and guilt share some neural networks, as well as having individual areas of activation. It can be concluded that frontal, temporal and limbic areas play a prominent role in the generation of moral feelings.
    Social Cognitive and Affective Neuroscience 10/2012; 9(2). DOI:10.1093/scan/nss114 · 7.37 Impact Factor
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    ABSTRACT: Recent analyses tried to explain the meaning of the Brief Psychiatric Rating Scale total score (BPRS) and its percentage change from baseline by equipercentile linking with the Clinical Global Impression Scale (CGI). A major limitation was that they were conducted in clinical trial populations limiting generalisability to 'real-world' patients. We therefore replicated the findings in a large sample covering patients admitted to a state hospital with a catchment area. BPRS and CGI ratings at admission (n=1772) and at discharge from all patients with schizophrenic disorders (ICD-10 F20.0-F20.9) admitted between 2005 and 2008 were compared using equipercentile linking. Being considered "mildly ill" according to the CGI severity score approximately corresponded to a BPRS total score of 25, "moderately ill" to a BPRS of 33-35, "markedly ill" to a BPRS of 50 and severely ill to a BPRS of 70. To be "minimally improved" according to the CGI change score was associated with a mean BPRS reduction of 13%; and "much improved" with 50% BPRS reduction. The linking functions were not identical, but overall comparable to those in previous randomised trial samples. The suggestion that a 50% BPRS reduction from baseline is a clinically meaningful definition of response in acutely ill patients was reinforced.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 02/2012; 22(7):501-5. DOI:10.1016/j.euroneuro.2011.11.007 · 4.37 Impact Factor
  • European Psychiatry 12/2011; 26:591-591. DOI:10.1016/S0924-9338(11)72298-2 · 3.44 Impact Factor
  • European Psychiatry 12/2011; 26:194-194. DOI:10.1016/S0924-9338(11)71904-6 · 3.44 Impact Factor
  • European Neuropsychopharmacology 09/2011; 21. DOI:10.1016/S0924-977X(11)70813-6 · 4.37 Impact Factor
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The decomposition of endophenotypes by means of experimental neuro-cognitive assessment has the potential to improve diagnostic assessment, evaluation of treatment response, and disentanglement of genetic and environmental influences. We assessed four parameters of attentional capacity and selectivity derived from simple psychophysical tasks (verbal report of briefly presented letter displays) and based on a "theory of visual attention." These parameters are mathematically independent, quantitative measures, and previous studies have shown that they are highly sensitive for subtle attention deficits. Potential reductions of attentional capacity, that is, of perceptual processing speed and working memory storage capacity, were assessed with a whole report paradigm. Furthermore, possible pathologies of attentional selectivity, that is, selection of task-relevant information and bias in the spatial distribution of attention, were measured with a partial report paradigm. A group of 30 unmedicated adult ADHD patients and a group of 30 demographically matched healthy controls were tested. ADHD patients showed significant reductions of working memory storage capacity of a moderate to large effect size. Perceptual processing speed, task-based, and spatial selection were unaffected. The results imply a working memory deficit as an important source of behavioral impairments. The theory of visual attention parameter working memory storage capacity might constitute a quantifiable and testable endophenotype of ADHD.
    Journal of Abnormal Psychology 08/2011; 120(4):890-901. DOI:10.1037/a0024944 · 4.86 Impact Factor
  • Cochrane Database of Systematic Reviews, 08/2011;
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    ABSTRACT: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds, however, low-potency antipsychotic drugs are often clinically perceived as less efficacious than high-potency compounds, and they also seem to differ in their side-effects.
    The Cochrane Library, 08/2011;

Publication Stats

6k Citations
801.74 Total Impact Points


  • 1995–2015
    • Ludwig-Maximilians-University of Munich
      • • Department of Psychiatry
      • • Hospital and Clinic of Psychiatry and Psychotherapy Poli
      München, Bavaria, Germany
  • 2000–2014
    • Technische Universität München
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie
      München, Bavaria, Germany
  • 2004
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 2002
    • Deutsches Herzzentrum München
      München, Bavaria, Germany