This foundational work comprehensively examines the current state of the genetics, genomics and brain circuitry of psychiatric and neurological disorders. It consolidates discoveries of specific genes and genomic regions associated with these conditions, the genetic and anatomic architecture of these syndromes, and addresses how recent advances in genomics are leading to a reappraisal of the biology underlying clinical neuroscience. In doing so, it critically examines the promise and limitations of these discoveries toward treatment, and to the interdisciplinary nature of understanding brain and behavior. Coverage includes new discoveries regarding autism, epilepsy, intellectual disability, dementias, movement disorders, language impairment, disorders of attention, schizophrenia, and bipolar disorder. Genomics, Circuits, and Pathways in Clinical Neuropsychiatry focuses on key concepts, challenges, findings, and methods in genetics, genomics, molecular pathways, brain circuitry, and related neurobiology of neurologic and psychiatric disorders.
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Table of Contents
Section 1 The Genome Tools and Methods1. The Newly Emerging View of the Genome
Stephan Sanders
2. Genetic Epidmeiology
Kathleen Ries Merikangas
3. Common Variation
Mark Daly
4. Rare/Structural Variation
Daniel Barrera and Jonathan Sebat
5. Epigenetics and Epigenomics
Eric J. Nestler and John Greally
6. Bioinformatics
Shaun Purcell
7. Imaging Genomics
Paul Matthew Thompson
8. Stem Cell Technology and Genomics
Alysson Renato Muotri
9. Association Strategies
Benjamin M. Neale
10. The promise of Systems Biology
Eric Schadt
11. Gene networks in neuropsychiatric disease
Daniel Geschwind
12. Mosaicism
Christopher A. Walsh and Saumya Shekhar Jamuar
Section 2 A new neuroanatomy
13. Mapping the Molecular Landscape of the Human Brain
Nenad Sestan
14. Studying Circuits
Stephan Lammel and Robert Malenka
15. Electrophysiological Measurement of Circuits
Srikantan S. Nagarajan
16. Imaging the Circuitry of the Human Brain
Michael Greicius
17. Neuroimaging Advances in Alzheimer's Disease
Daniel R. Schonhaut and Gil Rabinovici
18. Progressive Supranuclear Palsy and Related Parkinsonian Disorders
Jesse A. Brown and William Seeley
19. The Anatomy of Basal Ganglia Circuitry of Behavior
Nicholas Au Yong, Adrienne M. Keener, Yvette Bordelon, Carlos Portera-Cailliau and Nader Pouratian
20. Brainstem Circuitry of Behavior
Helmut Heisen
21. Apathy
Basal Ganglia, Frontal Circuits
Mario F. Mendez
22. Emotion Circuitry
Robert Wayne Levenson
23. Delusions
Georges Naasan
24. Hallucinations
Dennis Velakoulis
Section 3 Clinical Phenomenology
25. Intro: Risk Overlap Among Disorders
Patrick Sullivan
26. The conundrum of Clinical Characterization RDOC/ICD-10/DSM
Bruce N. Cuthbert
27. Schizophrenia
Aiden Corvin
28. Psychosis
Raquel E. Gur and Ruben Gur
29. ASD
Rebecca Ann Muhle, Stephan Sanders, Hannah Reed and Matthew William State
30. Bipolar Disorder
Nelson B. Freimer, Carrie E. Bearden and Peter Zandi
31. MDD
David C. Glahn
32. Speech and Language Disorders
Marilu Gorno-Tempini
33. Molecular Pathways Leading to the Clinical Phenomenology of Frontotemporal Dementia
Suzee Eurie Lee and Jennifer S. Yokoyama
34. Alzheimer's
Rudy Tanzi
35. PTSD
Kerry Ressler
36. Neurodevelopmental syndromes
Elliott Sherr
37. Epilepsies
Ryan S. Dhindsa, Daniel Lowenstein and David Goldstein
38. Substance Abuse
Nii Addy
39. Neuroimmunology
Emmanuel Mignot
40. Brain Tumors
Vanessa Clark and Murat Günel
41. White Matter Disorders
Michael David Geschwind and Brianne Magouirk Bettcher
42. ALS
Elena Ratti and James Berry
43. Eating Disorders
Cynthia M. Bulik and Garret Stuber
Section 4 Clinical Translation and Drug Development
44. Pharmacogenomics
Roy H. Perlis
Authors
Thomas Lehner National Institutes of Mental Health, Rockville, MD, USA.Dr. Thomas Lehner is the Director of the Office for Genomics Research Coordination at the National Institute of Mental Health (NIMH), National Institutes of Health (NIH). He oversees and coordinates all efforts associated with genomics research for the NIMH and is the principal advisor to the NIMH Director and the NIMH Scientific Director for issues related to genetics and genomics. A native of Vienna, Austria, he received a Ph.D. in genetics from the University of Vienna and an MPH in Epidemiology from Columbia University. Since joining NIMH in 2004 Thomas has been instrumental in developing Team Science as a new paradigm for psychiatric genomics and forging international collaborative efforts and consortia. He has also been instrumental in developing and consolidating genomics resources for the research community through participation in developing NIH data sharing policies for genomics including the Genomic Data Sharing (GDS) policy and its implementation.
Bruce L. Miller San Francisco School of Medicine, University of California at San Francisco, CA, USA.
Dr. Miller holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Neurology at the University of California, San Francisco (UCSF). He directs the busy UCSF dementia center where patients in the San Francisco Bay Area and beyond receive comprehensive clinical evaluations. His goal is the delivery of model care to all of the patients who enter the clinical and research programs at the UCSF Memory and Aging Center (MAC).
Dr. Miller is a behavioral neurologist focused on dementia with special interests in brain and behavior relationships as well as the genetic and molecular underpinnings of disease. His work in frontotemporal dementia (FTD) emphasizes both the behavioral and emotional deficits that characterize these patients, while simultaneously noting the visual creativity that can emerge in the setting of FTD. He is the principal investigator of the NIH-sponsored Alzheimer's Disease Research Center (ADRC) and program project on FTD called Frontotemporal Dementia: Genes, Imaging and Emotions. He oversees a healthy aging program, which includes an artist in residence program. In addition, he helps lead two philanthropy-funded research consortia, the Tau Consortium and Consortium for Frontotemporal Research, focused on developing treatments for tau and progranulin disorders, respectively. Also, he works with the National Football League to help with the education and assessment of players related to brain health. Dr. Miller teaches extensively, runs the Behavioral Neurology Fellowship at UCSF, and oversees visits of more than 50 foreign scholars every year.
Dr. Miller has received many awards including the Potamkin Award from the American Academy of Neurology, the Raymond Adams Lecture at the American Neurological Association, the Elliot Royer Award from the San Francisco Neurological community, the UCSF Annual Faculty Research Lectureship in Clinical Science, the UCSF Academic Senate Distinction in Mentoring Award, Distinguished Service to Minorities, from Charles Drew University, and the Gene D. Cohen Research Award in Creativity and Aging from the National Center for Creative Aging. He has authored The Human Frontal Lobes, The Behavioral Neurology of Dementia, Frontotemporal Dementia and over 600 other publications regarding dementia. He has been featured in Fortune magazine and The New York Times, as well as on "Charlie Rose," "PBS NewsHour" and other media. For more than three decades, Dr. Miller has been the scientific director for the philanthropic organization The John Douglas French Alzheimer's Foundation, a private philanthropic organization that funds basic science research in Alzheimer's disease.
Matthew W. State University of California at San Francisco, San Francisco, CA, USA.
Matthew W. State MD, PhD, is a child psychiatrist and human geneticist studying pediatric neuropsychiatric syndromes. His lab focuses on gene discovery as a launching point for efforts to illuminate the biology of these conditions and to develop novel and more effective therapies.
Dr. State received his undergraduate and medical degrees at Stanford University, completed his residency in psychiatry and fellowship in child psychiatry at the UCLA Neuropsychiatric Institute, and earned a PhD in genetics from Yale University. He was on the faculty at Yale from 2001 to 2013 where he was the Donald J. Cohen Professor of Child Psychiatry, Psychiatry and Genetics and the Co-Founder and Co-Director of the Yale Program on Neurogenetics. He is currently the Oberndorf Family Distinguished Professor and Chair of Psychiatry at UCSF and Director of the Langley Porter Psychiatric Institute and Hospital.
