LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 141

Search options

  1. Article ; Online: Ultrarare Coding Variants and Cognitive Function in Schizophrenia-Unraveling the Enduring Mysteries of Neuropsychiatric Genetics.

    Braff, David L / Bigdeli, Tim B

    JAMA psychiatry

    2022  Volume 79, Issue 10, Page(s) 946–948

    MeSH term(s) Cognition ; Genetic Predisposition to Disease ; Humans ; Schizophrenia/genetics
    Language English
    Publishing date 2022-08-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2701203-7
    ISSN 2168-6238 ; 2168-622X
    ISSN (online) 2168-6238
    ISSN 2168-622X
    DOI 10.1001/jamapsychiatry.2022.2030
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Clarifying directional dependence among measures of early auditory processing and cognition in schizophrenia: leveraging Gaussian graphical models and Bayesian networks.

    Abplanalp, Samuel J / Braff, David L / Light, Gregory A / Joshi, Yash B / Nuechterlein, Keith H / Green, Michael F

    Psychological medicine

    2024  , Page(s) 1–10

    Abstract: Background: Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for ... ...

    Abstract Background: Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for relationships among individual measures of cognition and EAP, thereby limiting their utility. Hence, EAP and cognition may function as complementary and interacting measures of brain function rather than independent stages of information processing. Here, we apply a data-driven approach to identifying directional relationships among neurophysiologic and cognitive variables.
    Methods: Using data from the Consortium on the Genetics of Schizophrenia 2, we estimated Gaussian Graphical Models and Bayesian networks to examine undirected and directed connections between measures of EAP, including mismatch negativity and P3a, and cognition in 663 outpatients with schizophrenia and 630 control participants.
    Results: Chain structures emerged among EAP and attention/vigilance measures in schizophrenia and control groups. Concerning differences between the groups, object memory was an influential variable in schizophrenia upon which other cognitive domains depended, and working memory was an influential variable in controls.
    Conclusions: Measures of EAP and attention/vigilance are conditionally independent of other cognitive domains that were used in this study. Findings also revealed additional causal assumptions among measures of cognition that could help guide statistical control and ultimately help identify early-stage targets or surrogate endpoints in schizophrenia.
    Language English
    Publishing date 2024-01-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 217420-0
    ISSN 1469-8978 ; 0033-2917
    ISSN (online) 1469-8978
    ISSN 0033-2917
    DOI 10.1017/S0033291724000023
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: The importance of endophenotypes in schizophrenia research.

    Braff, David L

    Schizophrenia research

    2015  Volume 163, Issue 1-3, Page(s) 1–8

    Abstract: Endophenotypes provide a powerful neurobiological platform from which we can understand the genomic and neural substrates of schizophrenia and other common complex neuropsychiatric disorders. The Consortium on the Genetics of Schizophrenia (COGS) has ... ...

    Abstract Endophenotypes provide a powerful neurobiological platform from which we can understand the genomic and neural substrates of schizophrenia and other common complex neuropsychiatric disorders. The Consortium on the Genetics of Schizophrenia (COGS) has conducted multisite studies on carefully selected key neurocognitive and neurophysiological endophenotypes in 300 families (COGS-1) and then in a follow up multisite case-control study of 2471 subjects (COGS-2). Endophenotypes are neurobiologically informed quantitative measures that show deficits in probands and their first degree relatives. They are more amenable to statistical analysis than are "fuzzy" qualitative clinical traits or confoundingly heterogeneous diagnostic categories. Endophenotypes are also viewed as uniquely informative in traditional diagnosis-based as well as emerging NIMH Research Domain (RDoC) contexts, offering a bridge between the two approaches to psychopathology classification and research. Endo- or intermediate phenotypes are heritable, and in the COGS-1 cohort their level of heritability is in the same range as is the heritability of schizophrenia itself, using the same statistical methods and subjects to assess both. Because we can demonstrate endophenotypes link to both gene networks and neural circuits on the one hand and also to real-life function, endophenotypes provide a critically important bridge for "connecting the dots" between genes, cells, circuits, information processing, neurocognition and functional impairment and personalized treatment selection in schizophrenia patients. By connecting schizophrenia risk genes with neurobiologically informed endophenotypes, and via the use of association, linkage, sequencing, stem cell and other strategies, we can provide our field with new neurobiologically informed information in our efforts to understand and treat schizophrenia. Evolving views, data and new analytic strategies about schizophrenia risk, pathology and treatment are described in this Viewpoint and in the accompanying Special Issue reports.
    MeSH term(s) Endophenotypes ; Family ; Genetic Predisposition to Disease ; Humans ; Multicenter Studies as Topic ; Schizophrenia/genetics ; Schizophrenia/physiopathology
    Language English
    Publishing date 2015-04
    Publishing country Netherlands
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639422-x
    ISSN 1573-2509 ; 0920-9964
    ISSN (online) 1573-2509
    ISSN 0920-9964
    DOI 10.1016/j.schres.2015.02.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Genomic substrates of neurophysiological endophenotypes: where we've been and where we're going.

    Braff, David L

    Psychophysiology

    2014  Volume 51, Issue 12, Page(s) 1323–1324

    Abstract: This special issue of Psychophysiology is focused on an imaginative and labor-intensive examination of the genomic substrates of heritable neurophysiological endophenotypes in the Minnesota Center for Twin and Family Research (MCTFR) cohorts. The authors ...

    Abstract This special issue of Psychophysiology is focused on an imaginative and labor-intensive examination of the genomic substrates of heritable neurophysiological endophenotypes in the Minnesota Center for Twin and Family Research (MCTFR) cohorts. The authors artfully combine the power of family-based behavioral data with the atheoretical genome-wide association study (GWAS) platform to enrich the examination of the genomic substrates of endophenotypes. Neurophysiological endophenotype deficits are found in psychiatric patients and are heritable in families of these psychiatric patients, allowing the investigators to combine the explanatory power of endophenotypes, with their known neural and functional substrates, with the otherwise agnostic identification of genes in the GWAS platform. This amplifies the power of the MCTFR endophenotype database. These well-considered studies add significantly to our understanding of normal human neurobiology and stimulate the use of these endophenotypes to expand our knowledge of the role of these measures and their genomic substrates in normal and psychopathology research.
    MeSH term(s) Brain/physiopathology ; Endophenotypes ; Genome-Wide Association Study ; Genotype ; Humans ; Mental Disorders/genetics ; Mental Disorders/physiopathology
    Language English
    Publishing date 2014-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209486-1
    ISSN 1540-5958 ; 0048-5772
    ISSN (online) 1540-5958
    ISSN 0048-5772
    DOI 10.1111/psyp.12352
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Understanding Connections and Boundaries Between Positive Symptoms, Negative Symptoms, and Role Functioning Among Individuals With Schizophrenia: A Network Psychometric Approach.

    Abplanalp, Samuel J / Braff, David L / Light, Gregory A / Nuechterlein, Keith H / Green, Michael F

    JAMA psychiatry

    2022  Volume 79, Issue 10, Page(s) 1014–1022

    Abstract: Importance: Improved understanding of the boundaries and connections between positive symptoms, negative symptoms, and role functioning in schizophrenia is critical, given limited empirical support for clear distinctions among these clinical areas. This ...

    Abstract Importance: Improved understanding of the boundaries and connections between positive symptoms, negative symptoms, and role functioning in schizophrenia is critical, given limited empirical support for clear distinctions among these clinical areas. This study's use of network psychometrics to investigate differential associations and structural overlap between positive symptoms, negative symptoms, and functional domains in schizophrenia may contribute to such understanding.
    Objective: To apply network analysis and community detection methods to examine the interplay and structure of positive symptoms, negative symptoms, and functional domains in individuals with schizophrenia.
    Design, setting, and participants: Cross-sectional study in 5 geographically distributed research centers in the US as part of the Consortium on the Genetics of Schizophrenia-2 from July 1, 2010, through January 31, 2014. Data were analyzed from November 2021 to June 2022. Clinically stable outpatients with schizophrenia or schizoaffective disorder were included. Participants were excluded if they had evidence of neurologic or additional Axis I psychiatric disorders. Other exclusion criteria included head injury, stroke, and substance abuse. Of 1415 patients approached, 979 were included in the final analysis.
    Main outcomes and measures: Measures included the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Role Functioning Scale. Main outcomes were expected influence, which assesses the relative importance of items to the network and is defined as the association of an item with all others, and community detection and stability, defined as the presence of statistical clusters and their replicability.
    Results: Participants with complete data included 979 outpatients (mean [SD] age, 46 [11] years; 663 male [67.7%]; 390 participants [40%] self-identified as African American, 30 [3%] as Asian, 7 [0.7%] as Native American, 8 [0.8%] as Pacific Islander, 412 [42.1%] as White, 125 [12.8%] as more than 1 race, and 5 [0.5%] did not identify). Anhedonia had the highest expected influence in the most comprehensive network analysis, showing connections with negative and positive symptoms and functional domains. Positive symptoms had the lowest expected influence. Community detection analyses indicated the presence of 3 clusters corresponding to positive symptoms; negative symptoms and work functioning; functional domains, including independent living, family relationships, and social network; and avolition, anhedonia, and work functioning. Hallucinations and delusions replicated in 1000 bootstrapped samples (100%), while bizarre behavior and thought disorder replicated in 390 (39%) and 570 (57%), respectively. In contrast, negative symptoms and work functioning replicated between 730 (73%) and 770 (77%) samples, respectively, and the remaining functional domains in 940 samples (94%).
    Conclusions and relevance: The high centrality of anhedonia and its connections with multiple functional domains suggest that it could be a treatment target for global functioning. Interventions for work functioning may benefit from a specialized approach that focuses primarily on avolition.
    MeSH term(s) Anhedonia ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Psychometrics ; Schizophrenia/drug therapy ; Schizophrenic Psychology
    Language English
    Publishing date 2022-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2701203-7
    ISSN 2168-6238 ; 2168-622X
    ISSN (online) 2168-6238
    ISSN 2168-622X
    DOI 10.1001/jamapsychiatry.2022.2386
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: The neuropsychiatric translational revolution: still very early and still very challenging.

    Braff, Lara / Braff, David L

    JAMA psychiatry

    2013  Volume 70, Issue 8, Page(s) 777–779

    MeSH term(s) Animals ; Genomics/methods ; Genomics/standards ; Genomics/trends ; Humans ; Neuropsychiatry/methods ; Neuropsychiatry/standards ; Neuropsychiatry/trends ; Translational Medical Research/methods ; Translational Medical Research/standards ; Translational Medical Research/trends
    Language English
    Publishing date 2013-06-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2701203-7
    ISSN 2168-6238 ; 2168-622X
    ISSN (online) 2168-6238
    ISSN 2168-622X
    DOI 10.1001/jamapsychiatry.2013.2184
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Gating in schizophrenia: from genes to cognition (to real world function?).

    Braff, David L

    Biological psychiatry

    2011  Volume 69, Issue 5, Page(s) 395–396

    MeSH term(s) Cognition/physiology ; Genotype ; Humans ; Neuropsychological Tests ; Phenotype ; Reflex, Startle/physiology ; Schizophrenia/genetics ; Schizophrenic Psychology ; Sensory Gating/physiology
    Language English
    Publishing date 2011-03-01
    Publishing country United States
    Document type Comment ; Introductory Journal Article
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2011.01.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article: Prepulse inhibition of the startle reflex: a window on the brain in schizophrenia.

    Braff, David L

    Current topics in behavioral neurosciences

    2011  Volume 4, Page(s) 349–371

    Abstract: Prepulse inhibition (PPI) of the startle response is an important measure of information processing deficits and inhibitory failure in schizophrenia patients. PPI is especially useful because it occurs in the same lawful manner in all mammals, from ... ...

    Abstract Prepulse inhibition (PPI) of the startle response is an important measure of information processing deficits and inhibitory failure in schizophrenia patients. PPI is especially useful because it occurs in the same lawful manner in all mammals, from humans to rodents, making it an ideal candidate for cross-species translational research. PPI deficits occur across the "schizophrenia spectrum" from schizophrenia patients to their clinically unaffected relatives. Parallel animal model and human brain imaging studies have demonstrated that PPI is modulated by cortico-striato-pallido-thalamic (and pontine) circuitry. This circuitry is also implicated in schizophrenia neuropathology and neurophysiology. The finding of PPI deficits in schizophrenia patients has been replicated by many groups, and these deficits correlate with measures of thought disorder and appear to be "normalized" by second generation antipsychotic (SGA) medications. Consistent pharmacological effects on PPI have been demonstrated; among these, dopamine agonists induce PPI deficits and (in animal models) these are reversed by first and SGA medications. PPI is also significantly heritable in humans and animals and can be used as a powerful endophenotype in studies of families of schizophrenia patients. Genomic regions, including the NRGL-ERBB4 complex with its glutamatergic influences, are strongly implicated in PPI deficits in schizophrenia. PPI continues to hold promise as an exciting translational cross-species measure that can be used to understand the pathophysiology and treatment of the schizophrenias via pharmacological, anatomic, and genetic studies.
    MeSH term(s) Antipsychotic Agents/pharmacology ; Antipsychotic Agents/therapeutic use ; Brain/drug effects ; Brain/physiopathology ; Dopamine/metabolism ; Dopamine/pharmacology ; Humans ; Inhibition (Psychology) ; Nicotine/pharmacology ; Reflex, Startle/drug effects ; Reflex, Startle/physiology ; Schizophrenia/drug therapy ; Schizophrenia/pathology ; Schizophrenia/physiopathology ; Sensory Gating/drug effects ; Sensory Gating/physiology
    Chemical Substances Antipsychotic Agents ; Nicotine (6M3C89ZY6R) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2011-02-11
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1866-3370
    ISSN 1866-3370
    DOI 10.1007/7854_2010_61
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Endophenotypes, Epigenetics, Polygenicity and More: Irv Gottesman's Dynamic Legacy.

    Braff, David L / Tamminga, Carol A

    Schizophrenia bulletin

    2016  Volume 43, Issue 1, Page(s) 10–16

    Abstract: First, we describe the hallmark contributions of Irv Gottesman's pioneering scholarship for schizophrenia research including concepts of polygenicity, gene × environment interactions, epigenetics and the endophenotype concept. Gottesman and colleagues' ... ...

    Abstract First, we describe the hallmark contributions of Irv Gottesman's pioneering scholarship for schizophrenia research including concepts of polygenicity, gene × environment interactions, epigenetics and the endophenotype concept. Gottesman and colleagues' twin studies showed that genes, not social factors, mediate schizophrenia risk. He then showed that schizophrenia is highly polygenic. Next, he introduced the concept of epigenetics into schizophrenia research. Gottesman then introduced the quantitative endophenotype concept. Endophenotypes are laboratory-based measures that show deficits in schizophrenia patients and lesser deficits in their first degree "unaffected" relatives and are viewed as being more proximal to genes and having a simpler genetic architecture than are "fuzzy" qualitative diagnostic disorders. Endophenotypes offer an exciting path to gene discovery, neural circuits, genetic architecture and new treatment pathways of schizophrenia and related psychotic disorders. Second, we were asked to discuss 2 of many endophenotype Consortia and related studies, in order to illustrate the impact of Gottesman's work. We describe the Consortium on the Genetics of Schizophrenia (COGS) exploring neurocognitive and neurophysiological endophenotypes in family and case-control studies. Association, linkage, sequencing and epigenetic studies are described. The Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) uses an array of endophenotypes including brain imaging in studies across the psychosis dimension, allowing for dimensional analyses. BSNIP results have led to the concept of biotypes, advancing the field. Irv Gottesman was imaginatively prescient in generating novel insights and predicting many major issues which challenge schizophrenia researchers who still use his concepts to guide current research approaches.
    MeSH term(s) Endophenotypes ; Epigenesis, Genetic ; Gene-Environment Interaction ; History, 20th Century ; History, 21st Century ; Humans ; Multifactorial Inheritance ; Schizophrenia/etiology ; Schizophrenia/genetics ; Schizophrenia/history
    Language English
    Publishing date 2016-11-21
    Publishing country United States
    Document type Biography ; Historical Article ; Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbw157
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article: Neurophysiologic Characterization of Resting State Connectivity Abnormalities in Schizophrenia Patients.

    Koshiyama, Daisuke / Miyakoshi, Makoto / Tanaka-Koshiyama, Kumiko / Joshi, Yash B / Molina, Juan L / Sprock, Joyce / Braff, David L / Light, Gregory A

    Frontiers in psychiatry

    2020  Volume 11, Page(s) 608154

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-11-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2020.608154
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top