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1.
Artigo em Inglês | MEDLINE | ID: mdl-33658653

RESUMO

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33751207

RESUMO

Glutamatergic neurotransmission dysfunction and the early involvement of the hippocampus have been proposed to be important aspects of the pathophysiology of schizophrenia. Here, we performed proteomic analysis of hippocampus postmortem samples from schizophrenia patients as well as neural cells-neurons and oligodendrocytes-treated with MK-801, an NMDA receptor antagonist. There were similarities in processes such as oxidative stress and apoptotic process when comparing hippocampus samples with MK-801-treated neurons, and in proteins synthesis when comparing hippocampus samples with MK-801-treated oligodendrocytes. This reveals that studying the effects of glutamatergic dysfunction in different neural cells can contribute to a better understanding of what it is observed in schizophrenia patients' postmortem brains.

3.
Respir Med ; 178: 106324, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33571924

RESUMO

BACKGROUND: Regarding the multiple health effects of e-cigarettes, there are insufficient data on potential effects on bronchial reactivity (BHR). In the present study, we assessed the impact of a switch from conventional to e-cigarettes on BHR under realistic conditions over a period of 3 months. METHODS: Sixty subjects who declared to reduce or stop their tobacco consumption by inhalation of nicotine-containing liquids via e-cigarette, and 20 volunteers participating in a stop-smoking program were included. Data was analysed using parametric and non-parametric statistical procedures. Spirometry, determinations of exhaled carbon monoxide (eCO) and nitric oxide (FeNO), provocation testing with mannitol as an indirect bronchial stimulus, and cotinine measurements were used to investigate BHR and nicotine abstinence. RESULTS: BHR to mannitol significantly decreased in the group using e-cigarettes and nicotine-containing liquids over a period of three months in this real-life setting. Participants reduced their tobacco consumption to about 25% or lower, confirmed by a reduction in eCO. Changes in lung function and FeNO were small and not statistically significant, and changes in the stop-smoking group were similar to those in the e-cigarette group. CONCLUSION: The reduction in BHR that can be expected after a reduction of cigarette consumption was not abolished by the concomitant use of e-cigarettes. Whether the decrease in BHR observed after 3 months is maintained when using e-cigarettes over longer time periods or has an individual prognostic value, must be clarified in long-term studies.

4.
Schizophr Res ; 228: 425-434, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33561620

RESUMO

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.

5.
Fortschr Neurol Psychiatr ; 89(1-02): 10-11, 2021 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-33465810
6.
Schizophr Res ; 228: 218-226, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33454644

RESUMO

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.

9.
MMW Fortschr Med ; 162(Suppl 7): 3-9, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33289913

RESUMO

CARE OF PATIENTS WITH MENTAL ILLNESS AND SARS-COV-2 INFECTION AT THE DEPARTMENT OF PSYCHIATRY AND PSYCHOTHERAPY LMU MUNICH, GERMANY : People with mental illness are particularly at risk in the event of a SARS-CoV-2 infection. In order to ensure their care, a 5-stage pandemic plan has been drawn up in the Clinic for Psychiatry and Psychotherapy at LMU Munich. This includes, among other things, which patients can be treated in the clinic, how registration is carried out, how the diagnosis is carried out and which treatment strategies are available. Predictors for severe disease progression are mentioned, as well as criteria for a transfer to intensive care unit. It is discussed when coercive measures are permitted in the treatment of patients with mental illness and SARS-CoV-2 infection.

11.
JAMA Psychiatry ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263726

RESUMO

Importance: Diverse models have been developed to predict psychosis in patients with clinical high-risk (CHR) states. Whether prediction can be improved by efficiently combining clinical and biological models and by broadening the risk spectrum to young patients with depressive syndromes remains unclear. Objectives: To evaluate whether psychosis transition can be predicted in patients with CHR or recent-onset depression (ROD) using multimodal machine learning that optimally integrates clinical and neurocognitive data, structural magnetic resonance imaging (sMRI), and polygenic risk scores (PRS) for schizophrenia; to assess models' geographic generalizability; to test and integrate clinicians' predictions; and to maximize clinical utility by building a sequential prognostic system. Design, Setting, and Participants: This multisite, longitudinal prognostic study performed in 7 academic early recognition services in 5 European countries followed up patients with CHR syndromes or ROD and healthy volunteers. The referred sample of 167 patients with CHR syndromes and 167 with ROD was recruited from February 1, 2014, to May 31, 2017, of whom 26 (23 with CHR syndromes and 3 with ROD) developed psychosis. Patients with 18-month follow-up (n = 246) were used for model training and leave-one-site-out cross-validation. The remaining 88 patients with nontransition served as the validation of model specificity. Three hundred thirty-four healthy volunteers provided a normative sample for prognostic signature evaluation. Three independent Swiss projects contributed a further 45 cases with psychosis transition and 600 with nontransition for the external validation of clinical-neurocognitive, sMRI-based, and combined models. Data were analyzed from January 1, 2019, to March 31, 2020. Main Outcomes and Measures: Accuracy and generalizability of prognostic systems. Results: A total of 668 individuals (334 patients and 334 controls) were included in the analysis (mean [SD] age, 25.1 [5.8] years; 354 [53.0%] female and 314 [47.0%] male). Clinicians attained a balanced accuracy of 73.2% by effectively ruling out (specificity, 84.9%) but ineffectively ruling in (sensitivity, 61.5%) psychosis transition. In contrast, algorithms showed high sensitivity (76.0%-88.0%) but low specificity (53.5%-66.8%). A cybernetic risk calculator combining all algorithmic and human components predicted psychosis with a balanced accuracy of 85.5% (sensitivity, 84.6%; specificity, 86.4%). In comparison, an optimal prognostic workflow produced a balanced accuracy of 85.9% (sensitivity, 84.6%; specificity, 87.3%) at a much lower diagnostic burden by sequentially integrating clinical-neurocognitive, expert-based, PRS-based, and sMRI-based risk estimates as needed for the given patient. Findings were supported by good external validation results. Conclusions and Relevance: These findings suggest that psychosis transition can be predicted in a broader risk spectrum by sequentially integrating algorithms' and clinicians' risk estimates. For clinical translation, the proposed workflow should undergo large-scale international validation.

12.
Cereb Cortex ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33279967

RESUMO

Neuregulin-1 (NRG1) represents an important factor for multiple processes including neurodevelopment, brain functioning or cognitive functions. Evidence from animal research suggests an effect of NRG1 on the excitation-inhibition (E/I) balance in cortical circuits. However, direct evidence for the importance of NRG1 in E/I balance in humans is still lacking. In this work, we demonstrate the application of computational, biophysical network models to advance our understanding of the interaction between cortical activity observed in neuroimaging and the underlying neurobiology. We employed a biophysical neuronal model to simulate large-scale brain dynamics and to investigate the role of polymorphisms in the NRG1 gene (rs35753505, rs3924999) in n = 96 healthy adults. Our results show that G/G-carriers (rs3924999) exhibit a significant difference in global coupling (P = 0.048) and multiple parameters determining E/I-balance such as excitatory synaptic coupling (P = 0.047), local excitatory recurrence (P = 0.032) and inhibitory synaptic coupling (P = 0.028). This indicates that NRG1 may be related to excitatory recurrence or excitatory synaptic coupling potentially resulting in altered E/I-balance. Moreover, we suggest that computational modeling is a suitable tool to investigate specific biological mechanisms in health and disease.

13.
Fortschr Neurol Psychiatr ; 88(12): 756-758, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33307560
14.
Fortschr Neurol Psychiatr ; 88(12): 778-785, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33307561

RESUMO

'Precision Psychiatry' as the psychiatric variant of 'Precision Medicine' aims to provide high-level diagnosis and treatment based on robust biomarkers and tailored to the individual clinical, neurobiological, and genetic constitution of the patient. The specific peculiarity of psychiatry, in which disease entities are normatively defined based on clinical experience and are also significantly influenced by contemporary history, society and philosophy, has so far made the search for valid and reliable psychobiological connections difficult. Nevertheless, considerable progress has now been made in all areas of psychiatric research, made possible above all by the critical review and renewal of previous concepts of disease and psychopathology, the increased orientation towards neurobiology and genetics, and in particular the use of machine learning methods. Notably, modern machine learning methods make it possible to integrate high-dimensional and multimodal data sets and generate models which provide new psychobiological insights and offer the possibility of individualized, biomarker-driven single-subject prediction of diagnosis, therapy response and prognosis. The aim of the present review is therefore to introduce the concept of 'Precision Psychiatry' to the interested reader, to concisely present modern, machine learning methods required for this, and to clearly present the current state and future of biomarker-based 'precision psychiatry'.

15.
J Autism Dev Disord ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373014

RESUMO

Individuals with Autism Spectrum Disorder (ASD) are thought to under-rely on prior knowledge in perceptual decision-making. This study examined whether this applies to decisions of attention allocation, of relevance for 'predictive-coding' accounts of ASD. In a visual search task, a salient but task-irrelevant distractor appeared with higher probability in one display half. Individuals with ASD learned to avoid 'attentional capture' by distractors in the probable region as effectively as control participants-indicating typical priors for deploying attention. However, capture by a 'surprising' distractor at an unlikely location led to greatly slowed identification of a subsequent target at that location-indicating that individuals with ASD attempt to control surprise (unexpected attentional capture) by over-regulating parameters in post-selective decision-making.

17.
Nervenarzt ; 2020 Oct 01.
Artigo em Alemão | MEDLINE | ID: mdl-33001264

RESUMO

In the clinical daily work of psychiatry, the question regularly arises under which legal conditions patients who are not able to form free will due to a mental illness should be treated in case of an additional suspicion of a SARS-CoV-2 infection or with a confirmed Covid-19 disease. However, physicians may be uncertain about the legal basis for coercive measures during the corona pandemic: when and under which legal conditions such measures are required. This article presents and discusses in detail the legal regulations currently applicable in Germany.

18.
BMC Psychiatry ; 20(1): 503, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046040

RESUMO

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.

19.
Nervenarzt ; 2020 Oct 06.
Artigo em Alemão | MEDLINE | ID: mdl-33025071

RESUMO

BACKGROUND: Since the beginning of the outbreak, the COVID-19 pandemic has caused an increased demand for psychosocial support for patients, their family members, and healthcare workers. Concurrently, possibilities to provide this support have been hindered. Quarantine, social isolation, and SARS-CoV­2 infections represent new and severe stressors that have to be addressed with innovative psychosocial care. OBJECTIVE AND METHOD: This article describes the COVID-19 psychosocial first aid concept at the University Hospital Munich (LMU Klinikum) developed by an interdisciplinary team of psychiatric, psychological, spiritual care, psycho-oncological, and palliative care specialists. RESULTS: A new psychosocial first aid model has been implemented for COVID-19 inpatients, family members, and hospital staff consisting of five elements. CONCLUSION: The concept integrates innovative and sustainable ideas, e.g. telemedicine-based approaches and highlights the importance of multidisciplinary collaboration to cope with challenges in the healthcare system.

20.
Aust N Z J Psychiatry ; : 4867420968912, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33111538

RESUMO

Deciding when and how to change treatment in patients with major depressive disorder who have inadequate response to initial antidepressant therapy is an important everyday clinical question. Here, we ask whether an early change of approach is superior to a delayed change. We consider the recommendations provided by recent guidelines, examine the evidence behind this guidance and suggest a decision tree to clarify treatment options and timing. Both the early and late-change strategies may have their place in clinical practice. However, we take the view that an earlier than currently usual change in antidepressant treatment should be considered more frequently in cases of non-response. Specific studies are needed to identify and to better understand predictors of early and late response.

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