Publications by authors named "Alkomiet Hasan"

176 Publications

Comparative Study of a Continuous Train of Theta-Burst Stimulation for a Duration of 20 s (cTBS 300) versus a Duration of 40 s (cTBS 600) in a Pre-Stimulation Relaxed Condition in Healthy Volunteers.

Brain Sci 2021 Jun 1;11(6). Epub 2021 Jun 1.

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, BKH Augsburg, Dr.-Mack-Str. 1, 86156 Augsburg, Germany.

As variable after effects have been observed following phasic muscle contraction prior to continuous theta-burst stimulation (cTBS), we here investigated two cTBS protocols (cTBS300 and cTBS600) in 20 healthy participants employing a pre-relaxed muscle condition including visual feedback on idle peripheral surface EMG activity. Furthermore, we assessed corticospinal excitability measures also from a pre-relaxed state to better understand the potential impact of these proposed contributors to TBS. Motor-evoked potential (MEP) magnitude changes were assessed for 30 min. The linear model computed across both experimental paradigms (cTBS300 and cTBS600) revealed a main effect of TIME COURSE ( = 0.044). Separate exploratory analysis for cTBS300 revealed a main effect of TIME COURSE ( = 0.031), which did not maintain significance after Greenhouse-Geisser correction ( = 0.073). For cTBS600, no main effects were observed. An exploratory analysis revealed a correlation between relative SICF at 2.0 ms ( = 0.006) and after effects (relative mean change) of cTBS600, which did not survive correction for multiple testing. Our findings thereby do not support the hypothesis of a specific excitability modulating effect of cTBS applied to the human motor-cortex in setups with pre-relaxed muscle conditions.
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http://dx.doi.org/10.3390/brainsci11060737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230207PMC
June 2021

Improvement in daily functioning after aerobic exercise training in schizophrenia is sustained after exercise cessation.

Eur Arch Psychiatry Clin Neurosci 2021 Jun 18. Epub 2021 Jun 18.

Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany.

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http://dx.doi.org/10.1007/s00406-021-01282-8DOI Listing
June 2021

Cannabis Use and Car Crashes: A Review.

Front Psychiatry 2021 28;12:643315. Epub 2021 May 28.

Clinic and Polyclinic for Psychiatry and Psychotherapy, Clinic of the Ludwig-Maximilian-University Munich, Munich, Germany.

In this review, state-of-the-art evidence on the relationship between cannabis use, traffic crash risks, and driving safety were analyzed. Systematic reviews, meta-analyses, and other relevant papers published within the last decade were systematically searched and synthesized. Findings show that meta-analyses and culpability studies consistently indicate a slightly but significantly increased risk of crashes after acute cannabis use. These risks vary across included study type, crash severity, and method of substance application and measurement. Some studies show a significant correlation between high THC blood concentrations and car crash risk. Most studies do not support this relationship at lower THC concentrations. However, no scientifically supported clear cut-off concentration can be derived from these results. Further research is needed to determine dose-response effects on driving skills combined with measures of neuropsychological functioning related to driving skills and crash risk.
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http://dx.doi.org/10.3389/fpsyt.2021.643315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195290PMC
May 2021

Effects of high-frequency prefrontal rTMS on heart frequency rates and blood pressure in schizophrenia.

J Psychiatr Res 2021 Aug 7;140:243-249. Epub 2021 Jun 7.

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, BKH, Augsburg, Germany.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a safe non-invasive neuromodulation technique used for the treatment of various neuropsychiatric disorders. The effect of rTMS applied to the cortex on autonomic functions has not been studied in detail in patient cohorts, yet patients who receive rTMS may have disease-associated impairments in the autonomic system and may receive medication that may pronounce autonomic dysfunctions.

Methods: Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we evaluated the effect of rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) on autonomic nervous system-related parameters such as blood pressure (BP) and heart rate (HR) in both reclining and standing postures from screening up to 105 days after intervention among patients with schizophrenia.

Results: 157 patients received either active (n = 76) or sham (n = 81) rTMS treatment. Apart from gender no significant group differences were observed. During intervention, Linear Mixed Model (LMM) analyses showed no significant time × group interactions nor time effects for any of the variables (all p > 0.055). During the whole trial beside a significant time × group interaction for diastolic BP (p = 0.017) in the standing posture, no significant time × group interactions for other variables (all p > 0.140) were found.

Conclusion: These secondary analyses of the largest available rTMS trial on the treatment of negative symptoms in schizophrenia did not show a significant effect of active rTMS compared to sham rTMS on heart rate or blood pressure, neither during the intervention period nor during the follow-up period.
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http://dx.doi.org/10.1016/j.jpsychires.2021.06.010DOI Listing
August 2021

Effects of Marathon Running on Cognition and Retinal Vascularization: A Longitudinal Observational Study.

Med Sci Sports Exerc 2021 May 24. Epub 2021 May 24.

Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany Department of Prevention and Sports Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany Deutsches Zentrum für Herz- und Kreislauf-Forschung (DZHK) e.V. (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany Institute of Medical Informatics, Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg, Bezirkskrankenhaus Augsburg, Medical Faculty, University of Augsburg, Augsburg, Germany University Center for Preventive and Sports Medicine, Balgrist University Hospital, University of Zurick, Zurich, Switzerland.

Introduction: Physical activity has beneficial effects on both cardiovascular and neurocognitive parameters, and these 2 modalities are known to interact at rest. However, findings on their interaction during exercise are inconclusive.

Purpose: Therefore, this longitudinal study aimed to investigate the effects of different forms of exercise (training period, marathon race, recovery period) on both parameters and their interaction.

Methods: We included 100 marathon runners (MA) (mean [SD] age: 43.6 [10.0] years, 80 male) and 46 age- and sex-matched sedentary controls (SC, for baseline comparison). Over the 6-month study period with 6 visits (12 and 2 weeks before the marathon; immediately, 24 hours, 72 hours and 12 weeks after the marathon), we assessed cognitive parameters by evaluating 1-to 3-back d prime, the d2 task, and the Trail Making Test A (TMTA) and B (TMTB); retinal vessel parameters by assessing arteriolar-to-venular ratio (AVR), central retinal arteriolar and venular equivalents (CRAE/CRVE).

Results: In the long-term analysis, 3-back d prime correlated positively with AVR (P = 0.024, B = 1.86,SE = 0.824) and negatively with CRVE (P = 0.05,B = -0.006,SE = 0.003) and TMTB correlated negatively with CRAE (P = 0.025,B = -0.155,SE = 0.069), even after correcting for age and systolic blood pressure as possible confounders. Acute effects were inconsistent with maximal cognitive improvement 24 hours after the marathon. AVR was significantly smaller in SC compared to MA.

Conclusion: Chronic exercise seems to prime the central nervous system for acute, intensive bouts of exercise. Our findings indicate a possible relationship between cognitive performance in high-demand tasks and retinal vasculature and support the idea of a neuroplastic effect of exercise.
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http://dx.doi.org/10.1249/MSS.0000000000002699DOI Listing
May 2021

Impact of the coronavirus disease 2019 pandemic on healthcare workers: systematic comparison between nurses and medical doctors.

Curr Opin Psychiatry 2021 07;34(4):413-419

Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg, Bezirkskrankenhaus Augsburg, Medical Faculty, University of Augsburg, Augsburg, German.

Purpose Of Review: The COVID-19 outbreak has had major impact on individual's psychological health and overall well being worldwide. Evidence shows that these psychological challenges are especially prominent in healthcare workers (HCW); especially in nurses. Indeed, several studies report that nurses suffer more psychologically because of the consequences of the pandemic compared with medical doctors. To further look into this, we systematically review the recent literature to see whether the psychological impact of the COVID-19 pandemic differs between medical doctors and nurses across studies and which aspects of mental health are especially affected in nurses.

Recent Findings: Across studies, there is solid evidence that nurses show poorer mental health outcomes compared with medical doctors during the COVID-19 pandemic. This is especially true for symptoms of depression, anxiety and posttraumatic stress disorder (PTSD). Here, prevalence rates in nurses are often higher than 50%. In contrast, general stress levels and burnout seem to be comparable between nurses and medical doctors.

Summary: Given that nurses suffer more from depression, anxiety and PTSD symptoms during the COVID-19 pandemic, special programs addressing their needs are required.
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http://dx.doi.org/10.1097/YCO.0000000000000721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183249PMC
July 2021

Employment status and desire for work in severe mental illness: results from an observational, cross-sectional study.

Soc Psychiatry Psychiatr Epidemiol 2021 Apr 16. Epub 2021 Apr 16.

Medical Faculty, Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.

Purpose: People with a severe mental illness (SMI) are at particular risk of occupational exclusion. Among the approaches to occupational rehabilitation, supported employment (SE) has been proven to be the most effective. A requirement to enter SE-programs is that individuals must want to seek competitive employment. The aim of this work is to investigate the relationship between serious mental illness and the desire to work including potential predictors.

Methods: This is a cross-sectional observational study of patients with SMI aged 18-65 years (n = 397). Patients were interviewed by trained staff using standardised instruments. The relationship between potential predictors and a strong preference for employment were analysed using a hierarchic binary logistic regression model.

Results: Only about one-quarter (27.9%) of SMI patients is in competitive employment. Another quarter is unemployed (25.9%). Results show that the desire for competitive employment is strong among more than half of the SMI patients. Among the unemployed, two-thirds express a strong desire for work. These individuals are an ideal target group for SE interventions. Comorbid chronic physical illness, diagnosis, and the subjectively judged ability to work are associated with the desire for work.

Conclusion: Our data confirm a substantial exclusion of individuals with SMI from the workforce. In general, care needs for workplace interventions are not being met and leave much room for improvement. In addition to employment status, the desire for work should be routinely assessed.

Study Registration: The study was registered in the German Clinical Trials Register (DRKS) ( https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015801 ) and under the WHO-Platform "International Clinical Trials Registry Platform" (ICTRP) ( https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00015801 ) under the registration number DRKS00015801 before the start of recruitment (Registration date: 21.02.2019).
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http://dx.doi.org/10.1007/s00127-021-02088-8DOI Listing
April 2021

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020).

Front Hum Neurosci 2020 23;14:568051. Epub 2021 Mar 23.

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.
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http://dx.doi.org/10.3389/fnhum.2020.568051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040977PMC
March 2021

The intervention, the patient and the illness - Personalizing non-invasive brain stimulation in psychiatry.

Exp Neurol 2021 Jul 31;341:113713. Epub 2021 Mar 31.

Laboratory of Neurosciences (LIM-27), Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo & Hospital Universitário, Universidade de São Paulo, Av. Prof Lineu Prestes 2565, 05508-000 São Paulo, Brazil.

Current hypotheses on the therapeutic action of non-invasive brain stimulation (NIBS) in psychiatric disorders build on the abundant data from neuroimaging studies. This makes NIBS a very promising tool for developing personalized interventions within a precision medicine framework. NIBS methods fundamentally vary in their neurophysiological properties. They comprise repetitive transcranial magnetic stimulation (rTMS) and its variants (e.g. theta burst stimulation - TBS) as well as different types of transcranial electrical stimulation (tES), with the largest body of evidence for transcranial direct current stimulation (tDCS). In the last two decades, significant conceptual progress has been made in terms of NIBS targets, i.e. from single brain regions to neural circuits and to functional connectivity as well as their states, recently leading to brain state modulating closed-loop approaches. Regarding structural and functional brain anatomy, NIBS meets an individually unique constellation, which varies across normal and pathophysiological states. Thus, individual constitutions and signatures of disorders may be indistinguishable at a given time point, but can theoretically be parsed along course- and treatment-related trajectories. We address precision interventions on three levels: 1) the NIBS intervention, 2) the constitutional factors of a single patient, and 3) the phenotypes and pathophysiology of illness. With examples from research on depressive disorders, we propose solutions and discuss future perspectives, e.g. individual MRI-based electrical field strength as a proxy for NIBS dosage, and also symptoms, their clusters, or biotypes instead of disorder focused NIBS. In conclusion, we propose interleaved research on these three levels along a general track of reverse and forward translation including both clinically directed research in preclinical model systems, and biomarker guided controlled clinical trials. Besides driving the development of safe and efficacious interventions, this framework could also deepen our understanding of psychiatric disorders at their neurophysiological underpinnings.
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http://dx.doi.org/10.1016/j.expneurol.2021.113713DOI Listing
July 2021

Multifactorial barriers in the implementation of schizophrenia and psychosocial therapies guidelines: A quantitative study across different professions.

Schizophr Res 2021 02 6;228:425-434. Epub 2021 Feb 6.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg, Bezirkskrankenhaus Augsburg, Medical Faculty, University of Augsburg, Augsburg, Germany.

Background: Clinical guidelines can facilitate the transfer of scientific evidence into clinical practice, yet their implementation still faces difficulties. The aim of this study was to examine the implementation status of the current German evidence- and consensus-based guidelines for schizophrenia (2019) and psychosocial therapies (2019) and to identify barriers as well as facilitators in guideline adherence.

Methods: We used a quantitative approach by developing an online questionnaire, focusing on the current implementation status as well as barriers and facilitators in guideline adherence. The questionnaire was sent to 100 hospitals for psychiatry and psychosomatics and 52 professional associations in mental healthcare in Germany (investigation period: 10/2019-01/2020).

Results: In total, 657 mental healthcare professionals (MHCP, e.g. medical doctors, psychologists, psychosocial therapists, caregivers) provided sufficient responses for analyses. Less than half (47%) of our participants were aware of the existence of the guideline for psychosocial therapies, while 74% exhibited awareness of the schizophrenia guideline. A minority reported to adhere to the current guidelines for schizophrenia (41%) and psychosocial interventions (18%). Profession-related differences in the implementation-status were detected. Specifically, medical doctors exhibited higher awareness rates than psychosocial therapists and caregivers and additionally higher adherence rates than psychologists and caregivers. Medical doctors were less exposed to knowledge-related barriers (e.g. lack of guideline familiarity), while no differences across professions were found in external/behavior-related barriers (e.g. long versions).

Discussion And Conclusion: Our findings indicate that the implementation of guidelines as well as related barriers vary between professions. To prevent a growing gap in guideline adherence between MHCP, target-specific implementation strategies should be considered.
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http://dx.doi.org/10.1016/j.schres.2021.01.010DOI Listing
February 2021

[Transcranial electrical brain stimulation methods for treatment of negative symptoms in schizophrenia].

Nervenarzt 2021 Jan 25. Epub 2021 Jan 25.

Klinik für Psychiatrie und Psychotherapie, Klinikum der Universität München, München, Deutschland.

In recent years noninvasive brain stimulation (NIBS) applications have emerged as a third and novel treatment option alongside psychopharmacology and psychotherapy in the treatment of mental diseases. It is assumed that NIBS could represent a supplement or (in some indications) even replacement to established therapeutic strategies, e.g. in disorders with high resistance to current treatment regimens, such as negative symptoms or cognitive impairments in schizophrenia. Although positive symptoms in schizophrenia can be treated sufficiently with antipsychotic drugs, patients with negative symptoms frequently suffer from persistent lack of impetus, cognitive decline, social withdrawal and loss of global functioning in the activities of daily life; however, in these cases, current treatment strategies exert only moderate effects, and new treatment options are urgently needed. This review article provides a summary of the clinical effects of new electrical NIBS methods, e.g. transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) for the treatment of negative symptoms in schizophrenia. These new NIBS methods could help restore the disrupted neuronal networks and improve disturbed connectivity, especially of the left dorsolateral prefrontal cortex and left temporoparietal junction. Promising results are reported for the treatment of negative symptoms with tDCS, tACS and tRNS and could thus represent new therapeutic options in the treatment of schizophrenia.
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http://dx.doi.org/10.1007/s00115-021-01065-5DOI Listing
January 2021

Characteristics and definitions of ultra-treatment-resistant schizophrenia - A systematic review and meta-analysis.

Schizophr Res 2021 02 14;228:218-226. Epub 2021 Jan 14.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.

Objective: The aim of this systematic review and meta-analysis was to characterize ultra-treatment-resistant Schizophrenia also known as clozapine-resistant schizophrenia (CRS) patients across clozapine combination and augmentation trials through demographic and clinical baseline data. Furthermore, we investigated the variability and consistency in CRS definitions between studies.

Methods: Systematic searches of articles indexed in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO were conducted in March 2020. 1541 randomized and non-randomized clinical trials investigating pharmacological and non-pharmacological clozapine add-on strategies were screened and a total of 71 studies were included. The primary outcome was the overall symptom score at baseline, measured with Positive and Negative Syndrome Scale (PANSS) total or Brief Psychiatric Rating Scale (BPRS) total scores.

Results: Data from 2731 patients were extracted. Patients were overall moderately ill with a mean PANSS total score at baseline of 79.16 (±7.52), a mean duration of illness of 14.64 (±4.14) years with a mean clozapine dose of 436.94 (±87.47) mg/day. Illness severity data were relatively homogenous among patients independently of the augmentation strategy involved, although stark geographical differences were found. Overall, studies showed a large heterogeneity of CRS definitions and insufficient guidelines implementation.

Conclusions: This first meta-analysis characterizing CRS patients and comparing CRS definitions revealed a lack of consistent implementation of a CRS definition from guidelines into clinical trials, compromising the replicability of the results and their applicability in clinical practice. We offer a new score modeled on a best practice definition to help future trials increase their reliability.
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http://dx.doi.org/10.1016/j.schres.2020.12.002DOI Listing
February 2021

Gamma transcranial alternating current stimulation for treatment of negative symptoms in schizophrenia: Report of two cases.

Asian J Psychiatr 2020 Dec 15;54:102423. Epub 2020 Sep 15.

Department of Psychiatry and Psychotherapy, Hospital of the University of Munich, Munich, Germany; Medical Park Chiemseeblick, Bernau-Felden, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2020.102423DOI Listing
December 2020

The revised DGPPN and APA schizophrenia guidelines: Guideline quality and recommendations for long-term antipsychotic treatment.

Schizophr Res 2021 03 15;229:137-139. Epub 2020 Nov 15.

Department of Psychiatry and Psychotherapy, Medical Faculty, LVR-Klinikum Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany; WHO Collaborating Centre on Quality Assurance and Empowerment in Mental Health, Düsseldorf, Germany.

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http://dx.doi.org/10.1016/j.schres.2020.11.011DOI Listing
March 2021

Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis.

Front Psychiatry 2020 29;11:569912. Epub 2020 Sep 29.

Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Objective: Avoiding withdrawal symptoms following antipsychotic discontinuation is an important factor when planning a safe therapy. We performed a systematic review and meta-analysis concerning occurrence of withdrawal symptoms after discontinuation of antipsychotics.

Data Sources: We searched the databases CENTRAL, Pubmed, and EMBASE with no restriction to the beginning of the searched time period and until October 1, 2019 (PROSPERO registration no. CRD42019119148).

Study Selection: Of the 18,043 screened studies, controlled and cohort trials that assessed withdrawal symptoms after discontinuation of oral antipsychotics were included in the random-effects model. Studies that did not implement placebo substitution were excluded from analyses. The primary outcome was the proportion of individuals with withdrawal symptoms after antipsychotic discontinuation. We compared a control group with continued antipsychotic treatment in the assessment of odds ratio and number needed to harm (NNH).

Data Extraction: We followed guidelines by the Cochrane Collaboration, PRISMA, and MOOSE.

Results: Five studies with a total of 261 individuals were included. The primary outcome, proportion of individuals with withdrawal symptoms after antipsychotic discontinuation, was 0.53 (95% CI, 0.37-0.70; = 82.98%, < 0.01). An odds ratio of 7.97 (95% CI, 2.39-26.58; = 82.7%, = 0.003) and NNH of 3 was calculated for the occurrence of withdrawal symptoms after antipsychotic discontinuation.

Conclusion: Withdrawal symptoms appear to occur frequently after abrupt discontinuation of an oral antipsychotic. The lack of randomized controlled trials with low risk of bias on antipsychotic withdrawal symptoms highlights the need for further research.
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http://dx.doi.org/10.3389/fpsyt.2020.569912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552943PMC
September 2020

Evaluation of evidence grades in psychiatry and psychotherapy guidelines.

BMC Psychiatry 2020 10 12;20(1):503. Epub 2020 Oct 12.

Department of Psychiatry and Psychotherapy, University Hospital Munich, Ludwig-Maximilians Universität München, Nußbaumstraße 7, 80336, München, Germany.

Background: Information regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines Network (SIGN) treatment guidelines, we aimed to specify how guideline recommendations are composed and to what extent recommendations are evidence-based.

Methods: Data was collected from all published evidence- and consensus-based S3-classified psychiatry and psychotherapy guidelines. As control conditions, data from German neurology S3-classified guidelines as well as data from recent SIGN guidelines of mental health were extracted. Two investigators reviewed the selected guidelines independently, extracted and analysed the numbers and levels of recommendations.

Results: On average, 45.1% of all recommendations are not based on strong scientific evidence in German guidelines of psychiatry and psychotherapy. A related pattern can be confirmed for SIGN guidelines, where the mean average of recommendations with lacking evidence is 33.9%. By contrast, in the German guidelines of neurology the average of such recommendations is 16.5%. A total of 24.5% of all recommendations in the guidelines of psychiatry and psychotherapy are classified as level A recommendations, compared to 31.6% in the field of neurology and 31.1% in the SIGN guidelines. Related patterns were observed for B and 0 level recommendations.

Conclusion: Guidelines should be practical tools to simplify the decision-making process based on scientific evidence. Up to 45% of all recommendations in the investigated guidelines of psychiatry and psychotherapy are not based on strong scientific evidence. The reasons for this high number remain unclear. Possibly, only a limited number of studies answer clinically relevant questions. Our findings thereby question whether guidelines should include non-evidence-based recommendations to be methodologically stringent and whether specific processes to develop expert-opinion statements must be implemented.
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http://dx.doi.org/10.1186/s12888-020-02897-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552557PMC
October 2020

Aberrant computational mechanisms of social learning and decision-making in schizophrenia and borderline personality disorder.

PLoS Comput Biol 2020 09 30;16(9):e1008162. Epub 2020 Sep 30.

Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and non-social information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and major depressive disorder patients showed the opposite pattern and schizophrenia patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder.
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http://dx.doi.org/10.1371/journal.pcbi.1008162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588082PMC
September 2020

Comparative study of motor cortical excitability changes following anodal tDCS or high-frequency tRNS in relation to stimulation duration.

Physiol Rep 2020 10;8(19):e14595

Department of Psychiatry and Psychotherapy, University Hospital Munich, München, Germany.

Background: In this study, we investigate the capacity of two different non-invasive brain stimulation (NIBS) techniques (anodal transcranial direct current stimulation (anodal tDCS) and high-frequency transcranial random noise stimulation (hf-tRNS)) regarding the relationship between stimulation duration and their efficacy in inducing long-lasting changes in motor cortical excitability.

Methods: Fifteen healthy subjects attended six experimental sessions (90 experiments in total) and underwent both anodal tDCS of 7, 13, and 20 min duration, as well as high-frequency 1mA-tRNS of 7, 13, and 20 min stimulation duration. Sessions were performed in a randomized order and subjects were blinded to the applied methods.

Results: For anodal tDCS, no significant stable increases of motor cortical excitability were observed for either stimulation duration. In contrast, for hf -tRNS a stimulation duration of 7 min resulted in a significant increase of motor cortical excitability lasting from 20 to 60 min poststimulation. While an intermediate duration of 13 min hf-tRNS failed to induce lasting changes in motor cortical excitability, a longer stimulation duration of 20 min hf-tRNS led only to significant increases at 50 min poststimulation which did not outlast until 60 min poststimulation.

Conclusion: Hf-tRNS for a duration of 7 min induced robust increases of motor cortical excitability, suggesting an indirect proportional relationship between stimulation duration and efficacy. While hf-tRNS appeared superior to anodal tDCS in this study, further systematic and randomized experiments are necessary to evaluate the generalizability of our observations and to address current intensity as a further modifiable contributor to the variability of transcranial brain stimulation.
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http://dx.doi.org/10.14814/phy2.14595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525483PMC
October 2020

Schizophrenia.

Dtsch Arztebl Int 2020 06;117(24):412-419

Department of Psychiatry, Psychotherapy, and Psychosomatics, Faculty of Medicine, University ofAugsburg, District Hospital Augsburg, AugsburgDepartment of Psychiatry and Psychotherapy, LMU Medical Center, MunichLVR Institute for Health Care Research, CologneDepartment of Psychiatry and Psychotherapy, LVR Hospital Düsseldorf, Faculty of Medicine,University of Düsseldorf.

Background: The lifetime prevalence of schizophrenia is 1%. Schizophrenia is among the most severe mental illnesses and gives rise to the highest treatment costs per patient of any disease. It is characterized by frequent relapses, marked impairment of quality of life, and reduced social and work participation.

Methods: The group entrusted with the creation of the German clinical practice guideline was chosen to be representative and pluralistic in its composition. It carried out a systematic review of the relevant literature up to March 2018 and identified a total of 13 389 publications, five source guidelines, three other relevant German clinical practice guidelines, and four reference guidelines.

Results: As the available antipsychotic drugs do not differ to any great extent in efficacy, it is recommended that acute antipsychotic drug therapy should be sideeffect- driven, with a number needed to treat (NNT) of 5 to 8. The choice of treatment should take motor, metabolic, sexual, cardiac, and hematopoietic considerations into account. Ongoing antipsychotic treatment is recommended to prevent relapses (NNT: 3) and should be re-evaluated on a regular basis in every case. It is also recommended, with recommendation grades ranging from strong to intermediate, that disorder- and manifestation-driven forms of psychotherapy and psychosocial therapy, such as cognitive behavioral therapy for positive or negative manifestations (effect sizes ranging from d = 0.372 to d = 0.437) or psycho-education to prevent relapses (NNT: 9), should be used in combination with antipsychotic drug treatment. Further aspects include rehabilitation, the management of special treatment situations, care coordination, and quality management. A large body of evidence is available to provide a basis for guideline recommendations, particularly in the areas of pharmacotherapy and cognitive behavioral therapy.

Conclusion: The evidence-based diagnosis and treatment of persons with schizophrenia should be carried out in a multiprofessional process, with close involvement of the affected persons and the people closest to them.
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http://dx.doi.org/10.3238/arztebl.2020.0412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477695PMC
June 2020

Subjective burden and perspectives of German healthcare workers during the COVID-19 pandemic.

Eur Arch Psychiatry Clin Neurosci 2021 Mar 19;271(2):271-281. Epub 2020 Aug 19.

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, BKH Augsburg, Dr.-Mack-Str. 1, 86156, Augsburg, Germany.

Healthcare workers (HCW) face tremendous challenges during the COVID-19 pandemic. Little is known about the subjective burden, views, and COVID-19 infection status of HCWs. The aim of this work was to evaluate the subjective burden, the perception of the information policies, and the agreement on structural measures in a large cohort of German HCW during the COVID-19 pandemic. This country-wide anonymous online survey was carried out from April 15th until May 1st, 2020. 25 content-related questions regarding the subjective burden and other dimensions were evaluated. We evaluated different dimensions of subjective burden, stress, and perspectives using 5-point Likert-scale questions. Moreover, the individual COVID-19 infection status, the amount of people infected in circle of friends and acquaintances and the hours working overtime were assessed. A total of 3669 HCWs provided sufficient responses for analyses. 2.8% of HCWs reported to have been tested positive for COVID-19. Nurses reported in principle higher ratings on all questions of subjective burden and stress than doctors and other hospital staff. Doctors (3.6%) and nurses (3.1%) were more likely to be tested positive for COVID-19 than other hospital staff (0.6%, Chi  = 17.39, p < 0.0005). HCWs who worked in a COVID-19 environment reported higher levels of subjective burden and stress compared to all other participants. Working in a COVID-19 environment increased the likelihood to be tested positive for COVID-19 (4.8% vs. 2.3%, Chi  = 12.62, p < 0.0005) and the severity of the subjective burden. During the COVID-19 pandemic, nurses experience more stress than doctors. Overall, German HCWs showed high scores of agreement with the measures taken by the hospitals.
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http://dx.doi.org/10.1007/s00406-020-01183-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437642PMC
March 2021

Effects of Smoking Status on Remission and Metabolic and Cognitive Outcomes in Schizophrenia Patients Treated with Clozapine.

Pharmacopsychiatry 2020 Nov 5;53(6):273-283. Epub 2020 Aug 5.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.

Background: Even though clozapine is the recommended last-resort antipsychotic, many patients fail to respond and show treatment-refractory psychotic symptoms. Smoking has been suggested as a possible risk factor for poor clozapine response, hampering remission and negatively impacting somatic outcomes.

Methods: Our aim was to test whether smoking status is associated with remission rates and other symptomatic and somatic outcomes. We therefore assessed remission rates according to The Remission in Schizophrenia Working Group (RSWG) criteria, and metabolic and cognitive outcomes among patients with schizophrenia-spectrum disorders treated with clozapine for at least 6 months. For analyses, we grouped our cohort into 3 groups according to clozapine treatment duration (6 months, 2 years, 5 years).

Results: One hundred five patients were included in our analyses and grouped according to their clozapine treatment duration. In the 6-months analyses, patients who smoked were significantly more likely to be younger of age (p=0.002) despite on average shorter duration of clozapine treatment (p=0.041) and significantly more likely to be treated with mood-stabilizing co-medication (p=0.030) compared to nonsmokers. Remission rates (p=0.490), as well as a set of metabolic and cognitive variables did not differ between the 2 groups. A related pattern could be observed for the 2- and 5-years analyses.

Conclusions: Smoking behavior among clozapine-treated schizophrenia patients might delineate a cohort with an earlier onset of the disease. Nevertheless, most findings comparing disease-specific and clinical outcomes among smokers and nonsmokers were negative. Further research is needed to identify strategies to overcome insufficient remission rates in this patient group.
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http://dx.doi.org/10.1055/a-1208-0045DOI Listing
November 2020

Aerobic endurance training to improve cognition and enhance recovery in schizophrenia: design and methodology of a multicenter randomized controlled trial.

Eur Arch Psychiatry Clin Neurosci 2021 Mar 3;271(2):315-324. Epub 2020 Aug 3.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany.

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients' health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40-50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients' mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).
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http://dx.doi.org/10.1007/s00406-020-01175-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257533PMC
March 2021

Gamma transcranial alternating current stimulation in patients with negative symptoms in schizophrenia: A case series.

Neurophysiol Clin 2020 Sep 4;50(4):301-304. Epub 2020 Jul 4.

Department. of Psychiatry and Psychotherapy, Klinikum der Universität München, Munich, Germany; Medical Park Chiemseeblick, 25, Rasthausstr, 83233 Bernau-Felden, Germany. Electronic address:

Non-invasive transcranial brain stimulation therapies, such as transcranial direct current stimulation, have been found to improve negative symptoms in schizophrenia. Another new technique is transcranial alternating current stimulation (tACS). Here we report a series of three patient treated with twice-daily 10min prefrontal 40Hz tACS stimulation over ten days. Patients showed an improvement in the Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and subjective well-being. Furthermore, there was an improvement in the Trail Making Test and word fluency. ytACS merits further investigation in the treatment of schizophrenia symptoms.
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http://dx.doi.org/10.1016/j.neucli.2020.06.004DOI Listing
September 2020

rTMS and tDCS for the treatment of catatonia: A systematic review.

Schizophr Res 2020 08 26;222:73-78. Epub 2020 Jun 26.

Department of Psychiatry and Psychotherapy, University Hospital Munich, Nußbaumstraße 7, 80336 München, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg, Bezirkskrankenhaus Augsburg, University of Augsburg, Medical Faculty, Augsburg, Germany.

Background: Catatonia is a potentially life threatening syndrome in various psychiatric disorders. As first line treatment, benzodiazepines and electroconvulsive therapy (ECT) are recommended. In some cases, benzodiazepines are ineffective and ECT is not available or contraindicated. Therefore, the search for new and alternative treatment strategies is of great importance.

Objective: To review the evidence for alternative neurostimulation treatment strategies (rTMS and tDCS) for catatonia according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Method: We performed a systematic literature search in several electronic databases. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov database to detect registered studies.

Results: We identified nine publications on rTMS treatment and four publications on tDCS in catatonia. Most of the publications reported clinically relevant improvement of catatonic symptoms. Only two publications reported insufficient improvement. The available Bush-Francis Catatonia Rating Scale scores showed statistical significant improvement following rTMS and tDCS. We could not identify any finished clinical studies or case series, dedicated to this topic. We also could not identify any publications that compared first line treatment options with rTMS or tDCS.

Conclusions: Based on the case report literature, rTMS and tDCS might be promising alternative treatment strategies for patients who do not respond to benzodiazepines or in case ECT is not available or contraindicated. There are even hints that rTMS or tDCS might be an option in patients who respond to ECT but need long-term treatment to control catatonic symptoms. Further clinical trials are needed to allow for an evidence-based evaluation of potential risks and benefits of rTMS and tDCS for catatonia.
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http://dx.doi.org/10.1016/j.schres.2020.05.028DOI Listing
August 2020

The two-way relationship between nicotine and cortical activity: a systematic review of neurobiological and treatment aspects.

Eur Arch Psychiatry Clin Neurosci 2021 Feb 27;271(1):157-180. Epub 2020 Jun 27.

Department of Psychiatry and Psychotherapy, University Medical Hospital, LMU, Nußbaumstr. 7, 80336, Munich, Germany.

Nicotine intake and cortical activity are closely related, as they can influence each other. Nicotine is implicated in the induction and modification of cortical plasticity and excitability, whereas a change on cortical plasticity and excitability can also lead to a modification of the smoking behaviour of an individual. The aim of this systematic review was, on the one hand, to evaluate the effects of nicotinergic modulation on cortical excitability and plasticity, and, on the other hand, to assess if modifying the brain's excitability and plasticity could influence one's smoking behaviour. Two systematic literature searches in the PubMed/MEDLINE and PsycINFO databases were conducted. Studies focusing either on the impact of nicotinergic modulation on cortical activity or the treatment effect of non-invasive brain stimulation techniques (NIBS) on smoking behaviour were included. A total of 22 studies for the first systematic search and 35 studies for the second one were included after full-text screening. Nicotine's effect on cortical activity appeared to depend on smoking status of the individual. While deprived smokers seem to generally profit from nicotine consumption in terms of cortical excitability and plasticity, the contrary was true for non-smokers. Regarding the questions of how changes in cortical excitability can influence smoking behaviour, a trend points towards NIBS being a potential intervention technique for smoking cessation.
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http://dx.doi.org/10.1007/s00406-020-01155-6DOI Listing
February 2021

Clozapine and COVID-19: The authors respond.

J Psychiatry Neurosci 2020 07;45(4):E1-E2

From the Metro South Addiction and Mental Health Service, Brisbane, Australia (Siskind); the University of Queensland, School of Clinical Medicine, Brisbane, Australia (Siskind, Myles); the Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada (Honer); the University of Adelaide, School of Medicine, Adelaide, Australia (Clark, Kane); the The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY, USA (Correll, Kane); the Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Molecular Medicine, Hempstead, NY, USA (Correll); the Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Berlin, Germany (Correll); the Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg, Augsburg, Germany (Hasan); the Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK (Howes); the MRC London Institute of Medical Sciences, Hammersmith Hospital, London, UK (Howes, MacCabe); the Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK (Howes); the Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA (Kelly); the Bronx Westchester Medical Group, New York, USA (Laitman); the North Region & Department of Psychosis, Institute of Mental Health, Singapore (Lee); the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore (Lee); the Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark (Nielsen); the Mental Health Service Noord-Holland-Noord, Alkmaar, The Netherlands (Schulte); the South London and Maudsley NHS Foundation Trust, Pharmacy Department, Maudsley Hospital, London, UK (Taylor); the University of Bordeaux, INSERM, Bordeaux Population Health Research Center, Bordeaux, France (Verdoux); the Menzies Health Institute Queensland, Griffith University, Brisbane, Australia (Wheeler); the MGH Schizophrenia Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA (Freudenreich); and the Harvard Medical School, Boston, Massachusetts, USA (Freudenreich).

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http://dx.doi.org/10.1503/jpn.2045302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828928PMC
July 2020

tDCS for auditory verbal hallucinations in a case of schizophrenia and left frontal lesion: efield simulation and clinical results.

Neurocase 2020 08 12;26(4):241-247. Epub 2020 Jun 12.

Department of Psychiatry and Psychotherapy, Klinikum der Universität München , Munich, Germany.

Transcranial direct current stimulation (tDCS) has been explored for treatment of several neuropsychiatric disorders. For tDCS use in structural brain lesions there is some evidence from motor stroke rehabilitation and post-stroke depression. Here we report the application of tDCS in a woman previously diagnosed with schizophrenia presenting refractory auditory verbal hallucinations and left prefrontal tissue lesion. Treatment with 20 left fronto-temporal tDCS had no effect on psychiatric symptoms and neuropsychological evaluation. An ex-post electric field simulation and calculation of dorsolateral prefrontal cortex activation showed lower activation in this patient compared to a matched non-lesioned schizophrenia, and healthy control brain.
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http://dx.doi.org/10.1080/13554794.2020.1776334DOI Listing
August 2020

Glutamatergic Contribution to Probabilistic Reasoning and Jumping to Conclusions in Schizophrenia: A Double-Blind, Randomized Experimental Trial.

Biol Psychiatry 2020 11 8;88(9):687-697. Epub 2020 Apr 8.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom; Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom.

Background: Impaired probabilistic reasoning and the jumping-to-conclusions reasoning bias are hallmark features of schizophrenia (SCZ), yet the neuropharmacological basis of these deficits remains unclear. Here we tested the hypothesis that glutamatergic neurotransmission specifically contributes to jumping to conclusions and impaired probabilistic reasoning in SCZ.

Methods: A total of 192 healthy participants received either NMDA receptor agonists/antagonists (D-cycloserine/dextromethorphan), dopamine type 2 receptor agonists/antagonists (bromocriptine/haloperidol), or placebo in a randomized, double-blind, between-subjects design. In addition, we tested 32 healthy control participants matched to 32 psychotic inpatients with SCZ-a state associated with compromised probabilistic reasoning due to reduced glutamatergic neurotransmission. All experiments employed two versions of a probabilistic reasoning (beads) task, which required participants to either sample individual amounts of sensory information to infer correct decisions or provide explicit probability estimates for presented sensory information. Our task instantiations assessed both information sampling and explicit probability estimates in different probabilistic contexts (easy vs. difficult conditions) and changing sensory information through random transitions among easy, difficult, and ambiguous trial types.

Results: Following administration of D-cycloserine, haloperidol, and bromocriptine, healthy participants displayed data-gathering behavior that was normal compared with placebo and was adequate in the context of all employed task conditions and trial level difficulties. However, healthy participants receiving dextromethorphan displayed a jumping-to-conclusions bias, abnormally increased probability estimates, and overweighting of sensory information. These effects were mirrored in patients with SCZ performing the same versions of the beads task.

Conclusions: Our findings provide novel neuropharmacological evidence linking reduced glutamatergic neurotransmission to impaired information sampling and to disrupted probabilistic reasoning, namely to overweighting of sensory evidence, in patients with SCZ.
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http://dx.doi.org/10.1016/j.biopsych.2020.03.018DOI Listing
November 2020
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