“More than ninety percent of the relatives of schizophrenics”: Deborah M. Barnes and Constance Holden, “Biological Issues in Schizophrenia,” Science, January 23, 1987.
The odds of siblings in the same family: Gottesman, Schizophrenia Genesis, 102–3.
about ten times the chance: Kevin Mitchell, Innate, 221.
higher, even, than heart disease or diabetes: Ibid.
The hippocampi of the brains…were smaller: R. L. Suddath, G. W. Christison, E. F. Torrey, M. F. Casanova, and D. R. Weinberger, “Anatomical Abnormalities in the Brains of Monozygotic Twins Discordant for Schizophrenia,” The New England Journal of Medicine 322, no. 12 (March 22, 1990): 789–94.
In 1987, Weinberger published a theory: Daniel R. Weinberger, “Implications of Normal Brain Development for the Pathogenesis of Schizophrenia,” Archives of General Psychiatry 44, no. 7 (July 1, 1987): 660.
what he called the “epigenetic landscape”: Weinberger and Harrison, Schizophrenia, 400.
“The risk is passed on”: Kevin Mitchell, Innate, 75.
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In 1997, Freedman identified CHRNA7: Robert Freedman, H. Coon, M. Myles-Worsley, A. Orr-Urtreger, A. Olincy, A. Davis, M. Polymeropoulos, et al., “Linkage of a Neurophysiological Deficit in Schizophrenia to a Chromosome 15 Locus,” Proceedings of the National Academy of Sciences of the United States of America 94, no. 2 (January 21, 1997): 587–92.
the first gene ever to be definitively associated with schizophrenia: Carol Kreck, “Mental Institute to Focus on Kids,” Denver Post, March 3, 1999.
By the year 2000, at least five more trouble areas would be isolated: Ann Schrader, “Schizophrenia Researchers Close in on Genetic Sources,” Denver Post, August 13, 2000.
In 1997, Freedman devised an experiment: Freedman et al., “Linkage of a Neurophysiological Deficit in Schizophrenia to a Chromosome 15 Locus.”
“important and exciting”: Denise Grady, “Brain-Tied Gene Defect May Explain Why Schizophrenics Hear Voices,” New York Times, January 21, 1997.
And when, in 2004, he tested: Laura F. Martin, William R. Kem, and Robert Freedman, “Alpha-7 Nicotinic Receptor Agonists: Potential New Candidates for the Treatment of Schizophrenia,” Psychopharmacology 174, no. 1 (June 1, 2004): 54–64.
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In 1994, The New England Journal of Medicine: William T. Carpenter and Robert W. Buchanan, “Schizophrenia,” New England Journal of Medicine 330, no. 10 (March 10, 1994): 681–90.
“arguably the worst disease affecting mankind, even AIDS not excepted”: “Where Next with Psychiatric Illness?,” Nature 336, no. 6195 (November 1988): 95–96.
“Dr. DeLisi and her collaborators”: “Sequana to Participate in Multinational Effort to Uncover the Genetic Basis of Schizophrenia,” Business Wire, April 20, 1995.
“beyond the practical capabilities of a small laboratory”: Ibid.
the largest single-investigator multiplex family study to date: Ibid.
The Human Genome Project: Bijal Trevedi, Michael Le Page, and Peter Aldhous, “The Genome 10 Years On,” New Scientist, June 19, 2010.
In 1995, the cancer researcher Harold Varmus: Samuel H. Barondes, Bruce M. Alberts, Nancy C. Andreasen, Cornelia Bargmann, Francine Benes, Patricia Goldman-Rakic, Irving Gottesman, et al., “Workshop on Schizophrenia,” Proceedings of the National Academy of Sciences of the United States of America 94, no. 5 (March 4, 1997): 1612–14.
Weinberger recalled Zach Hall: Transcript of an interview with Daniel Weinberger, conducted by Stephen Potkin at the 48th annual meeting of the American College of Neuropsychopharmacology in Boca Raton, Florida, December 12, 2007.
“thousands of common alleles”: Shaun M. Purcell, Naomi R. Wray, Jennifer L. Stone, Peter M. Visscher, Michael C. O’Donovan, Patrick F. Sullivan, and Pamela Sklar, “Common Polygenic Variation Contributes to Risk of Schizophrenia and Bipolar Disorder,” Nature 460, no. 7256 (August 6, 2009): 748–52.
copy number variations (CNVs): James R. Lupski, “Schizophrenia: Incriminating Genomic Evidence,” Nature 455, no. 7210 (September 2008): 178–79.
One GWAS, published in Nature Genetics in 2013: Stephan Ripke, Colm O’Dushlaine, Kimberly Chambert, Jennifer L. Moran, Anna K. Kähler, Susanne Akterin, Sarah E. Bergen, et al., “Genome-Wide Association Analysis Identifies 13 New Risk Loci for Schizophrenia,” Nature Genetics 45, no. 10 (August 25, 2013): 1150–59.
Another GWAS, published in Nature in 2014: Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T. R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, et al., “Biological Insights from 108 Schizophrenia-Associated Genetic Loci,” Nature 511, no. 7510 (July 22, 2014): 421–27.
“polygenic risk score”: Brien Riley and Robert Williamson, “Sane Genetics for Schizophrenia,” Nature Medicine 6, no. 3 (March 2000): 253–55. (The complete explanation of the risk score: “Analysis of concordance in first-, second- and third-degree relatives suggests that variants at three or more separate loci are required to confer susceptibility, and that these allelic variants increase risk in a multiplicative rather than additive manner, with the total risk being greater than the sum of the individual risks conferred by each variant.”)
by about 4 percent: Jonathan Leo, “The Search for Schizophrenia Genes,” Issues in Science and Technology 32, no. 2 (2016): 68–71.
“It’s sort of a mindless score”: Author’s interview with Elliot Gershon.
“The guess among my colleagues is that we’ll need 250,000 schizophrenia patients”: Author’s interview with Steven Hyman.
“Is it a classical organically based biomedical disorder”: Kenneth Kendler, “A Joint History of the Nature of Genetic Variation and the Nature of Schizophrenia,” Molecular Psychiatry 20, no. 1 (February 2015): 77–83.
“a disaster”: Joan Arehart-Treichel, “Psychiatric Gene Researchers Urged to Pool Their Samples,” Psychiatric News (American Psychiatric Association), November 16, 2007.
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being described as effective, safe, and even relatively painless: Scott O. Lilienfeld and Hal Arkowitz, “The Truth About Shock Therapy: Electroconvulsive Therapy Is a Reasonably Safe Solution for Some Severe Mental Illnesses,” Scientific American, May 1, 2014.
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