Begemann, Martin Johannes

[["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.contributor.author","Steixner-Kumar, Agnes A."],["dc.contributor.author","Daguano Gastaldi, Vinicius"],["dc.contributor.author","Seidel, Jan"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2021-06-01T09:41:38Z"],["dc.date.available","2021-06-01T09:41:38Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Considering the immense societal and personal costs and suffering associated with multiple drug use or “polytoxicomania”, better understanding of environmental and genetic causes is crucial. While previous studies focused on single risk factors and selected drugs, effects of early-accumulated environmental risks on polytoxicomania were never addressed. Similarly, evidence of genetic susceptibility to particular drugs is abundant, while genetic predisposition to polytoxicomania is unexplored. We exploited the GRAS data collection, comprising information on N~2000 deep-phenotyped schizophrenia patients, to investigate effects of early-life environmental risk accumulation on polytoxicomania and additionally provide first genetic insight. Preadult accumulation of environmental risks (physical or sexual abuse, urbanicity, migration, cannabis, alcohol) was strongly associated with lifetime polytoxicomania ( p   = 1.5 × 10 −45 ; OR = 31.4), preadult polytoxicomania with OR = 226.6 ( p  = 1.0 × 10 −33 ) and adult polytoxicomania with OR = 17.5 ( p  = 3.4 × 10 −24 ). Parallel accessibility of genetic data from GRAS patients and N~2100 controls for genome-wide association (GWAS) and phenotype-based genetic association studies (PGAS) permitted the creation of a novel multiple GWAS–PGAS approach. This approach yielded 41 intuitively interesting SNPs, potentially conferring liability to preadult polytoxicomania, which await replication upon availability of suitable deep-phenotyped cohorts anywhere world-wide. Concisely, juvenile environmental risk accumulation, including cannabis and alcohol as starter/gateway drugs, strongly predicts polytoxicomania during adolescence and adulthood. This pivotal message should launch more effective sociopolitical measures to prevent this deleterious psychiatric condition."],["dc.identifier.doi","10.1038/s41380-021-01069-2"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84988"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1476-5578"],["dc.relation.issn","1359-4184"],["dc.title","Preadult polytoxicomania—strong environmental underpinnings and first genetic hints"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","120"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Medicine"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Gross, Oliver"],["dc.contributor.author","Wincewicz, Dominik"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Daguano Gastaldi, Vinicius"],["dc.contributor.author","Vieta, Eduard"],["dc.contributor.author","Weissenborn, Karin"],["dc.contributor.author","Miskowiak, Kamilla W."],["dc.contributor.author","Moerer, Onnen"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2021-12-01T09:23:59Z"],["dc.date.accessioned","2022-08-16T12:53:14Z"],["dc.date.available","2021-12-01T09:23:59Z"],["dc.date.available","2022-08-16T12:53:14Z"],["dc.date.issued","2021-09-26"],["dc.date.updated","2022-07-29T12:18:56Z"],["dc.description.abstract","Background Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called \\‘long COVID\\’ and \\‘neuroCOVID\\’, becomes increasingly evident. Main body of the abstract Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term \\‘hypoxia paradox\\’. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this \\‘hypoxia paradox\\’ caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues. Short conclusion Substitution of EPO may—among other beneficial EPO effects in severe COVID-19—circumvent downstream consequences of the \\‘hypoxia paradox\\’. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted."],["dc.identifier.citation","Molecular Medicine. 2021 Sep 26;27(1):120"],["dc.identifier.doi","10.1186/s10020-021-00381-5"],["dc.identifier.pii","381"],["dc.identifier.pmid","34565332"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94813"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112749"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/44"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease"],["dc.relation.eissn","1528-3658"],["dc.relation.issn","1076-1551"],["dc.relation.workinggroup","RG Ehrenreich (Clinical Neuroscience)"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","Recombinant human EPO"],["dc.subject","Darbepoetin"],["dc.subject","Neuroprotection"],["dc.subject","Treatment"],["dc.subject","Signaling"],["dc.subject","Critical care"],["dc.subject","Outcome"],["dc.title","Addressing the ‘hypoxia paradox’ in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Brain, Behavior, and Immunity"],["dc.contributor.author","Daguano Gastaldi, Vinicius"],["dc.contributor.author","Bh Wilke, Justus"],["dc.contributor.author","Weidinger, Cosima A."],["dc.contributor.author","Walter, Carolin"],["dc.contributor.author","Barnkothe, Nadine"],["dc.contributor.author","Teegen, Bianca"],["dc.contributor.author","Luessi, Felix"],["dc.contributor.author","Stöcker, Winfried"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2022-12-01T08:31:58Z"],["dc.date.available","2022-12-01T08:31:58Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/j.bbi.2022.10.016"],["dc.identifier.pii","S0889159122004214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118322"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.issn","0889-1591"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Factors predisposing to humoral autoimmunity against brain-antigens in health and disease Analysis of 49 autoantibodies in over 7000 subjects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]