David Braff, M.D. is Distinguished Professor of Psychiatry, and Director of the Schizophrenia Program at the Department of Psychiatry, University of California San Diego School of Medicine. He is also Director and Lead Scientist of the NIH-funded multi-site Consortium on the Genetics of Schizophrenia (COGS). He trained at the University of Pennsylvania, Yale University, and the University of California, San Francisco.
David Braff’s research interests have received long-term NIMH and NARSAD Distinguished Investigator funding and a special NIMH MERIT Award to extend his research as well as funding from the Veterans Administration. His interests center around 1) the identification of neurocognitive and neurophysiological biomarker deficits in psychiatric disorders (with an emphasis on schizophrenia); 2) understanding the neural circuit/substrate dysfunctions of schizophrenia patients using human and cross-species translational animal model studies; 3) using neurocognitive, imaging, information processing, and attentional dysregulation as endophenotypes in family/genetic studies; 4) utilizing translational and genetic research tools to identify the neural circuit basis and the genetic architecture of neuropsychiatric disorders such as schizophrenia; and 5) utilizing genetically and behaviorally determined, strong inference-based targets for developing efficacious antipsychotic medications and psychosocial therapies that can improve the functional outcome and quality of life of schizophrenia patients and reduce the devastating disease burden placed on them and their families by this “no fault” clinical brain disorder.
David Braff has published over 250 articles and 300 reviews, book chapters and abstracts. He has received special recognition from the Institute for Scientific Information (ISI) as being in the top half of 1% of most highly cited neuropsychiatric researchers. In addition, he has been the Attending Physician for over 10,000 patients with schizophrenia and other serious mental disorders, and has trained many researchers and clinicians. Dr. Braff has served as Councilor, Executive Secretary and President of the Society of Biological Psychiatry (SOBP), and as a Councilor and President of the American College of Neuropsychopharmacology (ACNP), 2 world leading neuropsychiatric research societies. He has consulted to the Diagnostic and Statistical Manual (DSM IV and V) Committee of the APA, and Expert Treatment Committee of the American Psychiatric Association (APA). He is the Co-Chair of the Executive Committee and Director of the Clinical Neurosciences and Genomic Unit at the Veterans Administration VISN 22 Mental Illness, Research and Clinical Center (MIRECC) program in the Southwest United States which investigates psychosis and its treatment. He has also been a key figure in advancing the Mission of the International Congress on Schizophrenia Research (ICOSR) and liaisoned USA-Russia and USA-China cultural and grant cooperative projects. He served for 15 years as President of the campus-wide UCSD Faculty Association.
David Braff has received numerous Grants, Awards, and Prizes. A Fellow of the American Psychiatric Association (APA), Dr. Braff received the Kempf Research Prize and Marmor Award for excellence in biopsychosocial research from the APA, as well as the Gold Medal for lifetime research accomplishments from the SOBP, and the Warren Award for schizophrenia research from the ICOSR. He received the George Thompson Award from the SOBP for service to the field, the Dean Award for Schizophrenia Research Excellence from the American College of Psychiatrists (ACP) as well as Gold Medal for psychiatric research from Society of Biological Psychiatry with other awards. He has been selected by his peers as one of the “Best Doctors” in the United States and in San Diego. He serves on many national and international committees and societies, such as the Executive Committee of the MATRICS Project of the NIMH, which identified novel cognitive targets for antipsychotic medications, and other NIMH advisory committees that focus on issues such as the design and conduct of large clinical treatment trials. Dr. Braff is on the Editorial Boards of the Archives of General Psychiatry and five other journals and reviews manuscripts for over 20 Top Journals. He has lectured nationally and internationally on many topics in neuropsychiatric science and practice, and is recognized as a leader of the international neuropsychiatric community.
- Jernigan TL, Zisook S, Heaton RK, Moranville JT, Hesselink JR, Braff DL. Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia. Arch Gen Psychiatry 48:881-890, 1991. (See 78 in CV). Significance: This paper was one of the first to use advanced quantitative MR imaging in schizophrenia. Results gave support to emerging ideas of cortical deficits and genomically determined “failure to prune” neurodevelopmental abnormalities in schizophrenia patients. Crucial subcortical brain areas were found to be larger than normal reflecting a potential neurodevelopmentally determined “failure to prune”. Cortical areas showed abnormal loss of volume, consistent with neurodegeneration in schizophrenia.
- Braff DL, Grillon C, Geyer MA. Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49(3):206-15, 1992. (See 81 in CV). Significance: Since Braff et al.’s first published study of gating deficits of the startle reflex (prepulse inhibition (PPI)) in schizophrenia patients, PPI has been perhaps the most studied biomarker in cross species research in neuropsychiatry. There have been over 3,000 citations on PPI since Braff et al.’s first experiment in Noch Callaway’s lab at UCSF. PPI of the startle reflex has informed the neural circuit basis of schizophrenia and other neuropsychiatric disorder revealing cortico-striato-pallido-thalamic (CSPT) modulatory circuit deficits leading to inhibitory deficits. PPI deficits have been the most widely used technique to assess antipsychotic efficacy in human and animal models of schizophrenia.
- Light GA & Braff DL. Mismatch Negativity Deficits are Associated with Poor Functioning in Schizophrenia Patients. Arch Gen Psychiatry 62:127-136, 2005. (See 191 in CV). Significance: With Gregory Light, Ph.D., Braff continued to explore the information processing deficits and neural circuit dysfunction of schizophrenia patients. We helped to develop and apply mismatch negativity (MMN), a paradigm where redundant “typical” stimuli occur, say 90% of the time and “deviant” (longer duration, pitch-deviant, louder) stimuli occur 10% of the time. The deviant stimuli elicit the MMN wave, even in infrahuman mammals, in fetuses in utero and neonates immediately postpartum. We reported here that MMN deficits correlate at 0.7 with real world functional deficits. This association level is equal to or exceeds the level of association of any neurocognitive biomarker with functional outcome in schizophrenia.
- Braff DL, Freedman R, Schork NJ, Gottesman II. Deconstructing Schizophrenia: An Overview of the Use of Endophenotypes in Order to Understand a Complex Disorder. Schizophr Bull 33:21-32, 2007. (See 209 in CV). Significance: This highly cited article is significant because it integrated disparate findings in the context of the world of genetically mediated endophenotypes. I was Guest Editor of this issue of Schizophrenia Bulletin, which presented articles and described the Consortium on the Genetics of Schizophrenia (COGS), the NIMH multi-site study of which I am Director. My co-authors are each distinguished scientists in the world of neuropsychiatric genetics and schizophrenia research. Quantitative endophenotypes are “closer” to gene products than are “fuzzy” qualitative diagnostic categories and offer a powerful strategy for gene hunting in patients.
- Greenwood TA, Swerdlow NR, Gur RE, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RC, Lazzeroni LC, Nuechterlein KH, Olincy A, Radant AD, Ray A, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Sugar CA, Tsuang DW, Tsuang MT, Turetsky BI, Light GA, Braff DL. Genome-Wide Linkage Analyses of 12 Endophenotypes for Schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS). Am J Psychiatry 170:521-32, 2013. (See 247 in CV).
- Greenwood TA, Lazzeroni LC, Murray SS, Cadenhead KS, Calkins ME, Dobie DJ, Green MF, Gur RE, Hardiman G, Kelsoe JR, Leonard S, Light GA, Nuechterlein KH, Olincy A, Radant AD, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Freedman R, Braff DL. Analysis of 94 candidate genes and 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am J Psychiatry 168:930-46, 2011.
Significance: As COGS Lead Scientist, I applied for and received 2 NIMH R01s and the National Alliance for Research on Schizophrenia and Depression (NARSAD) Distinguished Investigator Award that funded this work. First, Dr. Greenwood and I selected the 1536 Single Nucleotide Polymorphisms (SNPs) based on a thorough review of the relevant mammalian biology and schizophrenia literature. We interrogated 94 functionally relevant candidate genes for schizophrenia and identified significant associations with the 12 heritable neurophysiological and neurocognitive COGS endophenotypes. A novel bootstrap total significance test (TST) was developed to overcome the limitations of existing genomic multiple testing methods and robustly demonstrate the presence of significant associations in a 42 gene network in the context of complex family data. Next, we conducted this linkage study in 300 families, identifying and replicating multiple linkage/gene loci of significance for understanding schizophrenia. This family based linkage study is the first step in identifying other schizophrenia-related genomic abnormalities such as de novo mutations (e.g., Gulsuner et al., Spatial and Temporal Mapping of De novo Mutations in Schizophrenia To a Fetal Prefrontal Cortical Network, Cell Aug. 2013, DL Braff, co-author), methylation events and gene expression profiles in 3 other funded NIMH projects and in COGS-2, a 3,000 subject case-control, intermediate phenotype follow-up on the COGS-1 family study.
- Braff L, Braff DL. The Neuropsychiatric Translational Revolution: Still Very Early and Still Very Challenging. JAMA Psychiatry “View Point” 70(8):777-9, 2013. Significance: There are many strategies for identifying the neurobiological (genomic and circuit based) substrates and functional significance of abnormalities found in schizophrenia patients and their relatives. The field is facing profound challenges regarding how to interpret the extensive interlocking data on the biology of schizophrenia and its treatment. In this “Viewpoint”, the scientific neuropsychiatric revolution (cf. Braff DL. Promises, Challenges and Caveats of Translational Research in Neuropsychiatry. In: Barrett JE, Coyle JT, Williams M (Eds.); Translational neuroscience: Applications in Neurology, Psychiatry, and neurodevelopmental Disorders. Cambridge University Press, pp. 339-358, 2012) is examined in a broad context of the history of social and scientific revolutions. Critical research pathways are delineated for understanding serious mental illness (SMI) and its treatment. This is a “revolution” that will have significant short term accomplishments but also requires reflective patience as we await genomically and neurobiologically guided treatments in the moderately “far” future.