Hidden Valley Road: Inside the Mind of an American Family (40 page)
Read Hidden Valley Road: Inside the Mind of an American Family Online
Authors: Robert Kolker
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.
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.
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.
Researchers predisposed against the reflexive use of medication
:
Whitaker,
Mad in America,
207–8.
Sure enough, with the Galvins, DeLisi and McDonough found something
:
O. R. Homann, K. Misura, E. Lamas, R. W. Sandrock, P. Nelson, Stefan McDonough, and Lynn E. DeLisi, “Whole-Genome Sequencing in Multiplex Families with Psychoses Reveals Mutations in the SHANK2 and SMARCA1 Genes Segregating with Illness,”
Molecular Psychiatry
21, no. 12 (December 2016): 1690–95.
a team from the Broad Institute in Cambridge
:
Aswin Sekar, Allison R. Bialas, Heather de Rivera, Avery Davis, Timothy R. Hammond, Nolan Kamitaki, et al., “Schizophrenia Risk from Complex Variation of Complement Component 4,”
Nature
530, no. 7589 (February 2016): 177–83.
others had conducted separate studies
:
Audrey Guilmatre, Guillaume Huguet, Richard Delorme, and Thomas Bourgeron, “The Emerging Role of SHANK Genes in Neuropsychiatric Disorders: SHANK Genes in Neuropsychiatric Disorders,”
Developmental Neurobiology
74, no. 2 (February 2014): 113–22. Also see Ahmed Eltokhi, Gudrun Rappold, and Rolf Sprengel, “Distinct Phenotypes of SHANK2 Mouse Models Reflect Neuropsychiatric Spectrum Disorders of Human Patients with SHANK2 Variants,”
Frontiers in Molecular Neuroscience
11 (2018).
“a collection of neurodevelopmental disorders”
:
Thomas R. Insel, “Rethinking Schizophrenia,”
Nature
468, no. 7321 (November 11, 2010): 187–93.
Another study of SHANK2 and schizophrenia
:
S. Peykov, S. Berkel, M. Schoen, K. Weiss, F. Degenhardt, J. Strohmaier, B. Weiss, et al., “Identification and Functional Characterization of Rare
SHANK2
Variants in Schizophrenia,”
Molecular Psychiatry
20, no. 12 (December 2015): 1489–98.
The geneticist Kevin Mitchell has noted
:
Kevin Mitchell,
Innate
, 233–34.
Freedman’s study about choline was published in 2016
:
Randal G. Ross, Sharon K. Hunter, M. Camille Hoffman, Lizbeth McCarthy, Betsey M. Chambers, Amanda J. Law, Sherry Leonard, Gary O. Zerbe, and Robert Freedman, “Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation,”
The American Journal of Psychiatry
173, no. 5 (May 2016): 509–16.
In 2017, the American Medical Association approved a resolution
:
Carrie Dennett: “Choline: The Essential but Forgotten Nutrient,”
Seattle Times,
November 2, 2017.
“Like riding the merry-go-round”
:
Rue L. Cromwell, “Strategies for Studying Schizophrenic Behavior,”
Psychopharmacologia
24, no. 1 (March 1, 1972): 121–46.
Hearing Voices Movement
:
Leudar and Thomas,
Voices of Reason, Voices of Insanity
.
many schizophrenia patients experience favorable long-term outcomes without prescription drugs
:
M. Harrow and T. H. Jobe, “Does Long-Term Treatment of Schizophrenia with Antipsychotic Medications Facilitate Recovery?,”
Schizophrenia Bulletin
39, no. 5 (September 1, 2013): 962–65. Also see M. Harrow, T. H. Jobe, and R. N. Faull, “Does Treatment of Schizophrenia with Antipsychotic Medications Eliminate or Reduce Psychosis? A 20-Year Multi-Follow-up Study,”
Psychological Medicine
44, no. 14 (October 2014): 3007–16.
more evidence that psychosis exists on a spectrum
:
S. Guloksuz and J. van Os, “The Slow Death of the Concept of Schizophrenia and the Painful Birth of the Psychosis Spectrum,”
Psychological Medicine
48, no. 2 (January 2018): 229–44.
One meta-analysis, published in 2013
:
R. J. Linscott and J. van Os. “An Updated and Conservative Systematic Review and Meta-Analysis of Epidemiological Evidence on Psychotic Experiences in Children and Adults: On the Pathway from Proneness to Persistence to Dimensional Expression Across Mental Disorders,”
Psychological Medicine
43, no. 6 (June 2013): 1133–49.
another study in 2015
:
John J. McGrath, Sukanta Saha, Ali Al-Hamzawi, Jordi Alonso, Evelyn J. Bromet, Ronny Bruffaerts, José Miguel Caldas-de-Almeida, et al., “Psychotic Experiences in the General Population: A Cross-National Analysis Based on 31,261 Respondents from 18 Countries,”
JAMA Psychiatry
72, no. 7 (July 1, 2015): 697–705.
“early detection and intervention model of care”
:
“Early Detection and Prevention of Psychotic Disorders: Ready for ‘Prime Time’?,” lecture by Jeffrey Lieberman for the Brain and Behavior Research Foundation, February 12, 2019.
so-called “soft interventions”
:
John M. Kane, Delbert G. Robinson, Nina R. Schooler, Kim T. Mueser, David L. Penn, Robert A. Rosenheck, Jean Addington, et al., “Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes from the NIMH RAISE Early Treatment Program,”
American Journal of Psychiatry
173, no. 4 (October 20, 2015): 362–72.
Australia and Scandinavia
:
Benedict Carey, “New Approach Advised to Treat Schizophrenia,”
New York Times,
December 21, 2017.
Lieberman at Columbia is developing
:
“Early Detection and Prevention of Psychotic Disorders: Ready for ‘Prime Time’?,” lecture by Jeffrey Lieberman for the Brain and Behavior Research Foundation, February 12, 2019.
whether the risk of schizophrenia is linked to the condition of an expectant mother’s placenta
:
Gianluca Ursini, Giovanna Punzi, Qiang Chen, Stefano Marenco, Joshua F. Robinson, Annamaria Porcelli, Emily G. Hamilton, Daniel Weinberger, et al., “Convergence of Placenta Biology and Genetic Risk for Schizophrenia,”
Nature Medicine,
May 28, 2018, 1.
“half of all young school shooters have symptoms of developing schizophrenia”
:
Peter Langman, “Rampage School Shooters: A Typology,”
Aggression and Violent Behavior
14 (2009): 79–86.
In 2016, the same year as her SHANK2 study, she published a paper
:
Lynn E. DeLisi, “A Case for Returning to Multiplex Families for Further Understanding the Heritability of Schizophrenia: A Psychiatrist’s Perspective,”
Molecular Neuropsychiatry
2, no. 1 (January 8, 2016): 15–19.
“Emotions are always accompanied…”
:
Arieti,
Interpretation of Schizophrenia,
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