Nav: Home

Genomic copy number variants contribute to cognitive impairment in the UK

June 28, 2017

Philadelphia, PA, June 28, 2017 - Genetic alterations of rare deletions or duplications of small DNA segments, called copy number variants (CNVs), have been known to increase risk of neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, and intellectual disability. Now, a new study in Biological Psychiatry reports that even in the absence of a disorder, people carrying a CNV associated with these disorders may have impaired cognition.

Led by Dr. George Kirov of Cardiff University MRC Centre for Neuropsychiatric Genetics & Genomics, UK, the study provides the largest analysis to date on the effects of CNVs on cognition in a general population -- most previous studies have focused on disease populations. The findings help researchers understand the effects of neurodevelopmental genetic abnormalities, even when they don't lead to the emergence of a disease.

"Psychiatric disorders are relatively extreme neuropsychiatric conditions. This study makes the case that CNVs that have been implicated in the risk for these disorders more directly produce subtle intellectual and functional changes that may be of great importance to these people and to society," said Dr. John Krystal, Editor of Biological Psychiatry.

In the study, first author Dr. Kimberley Kendall, also of Cardiff University, and colleagues analyzed data from the UK Biobank, a repository of extensive demographic, health, and cognitive data from 500,000 adults. The first nearly 152,000 of those have also been genotyped and were included in the study. Kendall and colleagues focused on CNVs that have been statistically linked with risk of neurodevelop-mental disorders (neurodevelopmental CNVs), including 12 schizophrenia-associated CNVs and a group of 41 CNVs associated with other disorders.

In a comparison of performance on cognitive tests between adults with schizophrenia, carriers of neurodevelopmental CNVs who were otherwise healthy, and people who did not carry any CNVs in their genome (noncarriers), those with schizophrenia performed the worst. Performance of carriers fell in between noncarriers and people with schizophrenia. Carriers also had lower educational attainment and tended to have occupations requiring less skill or training. No differences were found between carriers of the 12 schizophrenia-associated CNVs versus carriers of the other neurodevelopmental CNVs.

However, there was a lot of overlap between the schizophrenia, carrier, and noncarrier groups. "The cognitive performance of carriers of schizophrenia-associated CNVs was indeed reduced, but the differences were subtle and a large proportion of CNV carriers appeared to function very well," said Kirov, adding that many CNV carriers reached very high levels of academic achievement, and successfully obtain highly skilled or cognitively demanding occupations.

The findings fill gaps in the knowledge of the effects of CNVs in adults from the general population, and extend previous reports of incomplete penetrance, where adults carrying CNVs who don't develop a disorder may still have an increased burden of cognitive impairments.

"The study hints at the huge potential of the UK Biobank for further research into the role of CNVs in human health and disease, and the opportunities it affords to study the effect of CNVs on carriers who are being followed up for many years for their psychiatric, cognitive and medical outcomes," said Kirov.
-end-
Notes for editors

The article is "Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects," by Kimberley M. Kendall, Elliott Rees, Valentina Escott-Price, Mark Einon, Rhys Thomas, Jonathan Hewitt, Michael C. O'Donovan, Michael J. Owen, James T.R. Walters, and George Kirov (http://dx.doi.org/10.1016/j.biopsych.2016.08.014). It appears in Biological Psychiatry, volume 82, issue 2 (July 2017), published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@UTSouthwestern.edu or +1 214 648 0880. Journalists wishing to interview the authors may contact George Kirov, Ph.D., at kirov@cardiff.ac.uk.

The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 5th out of 140 Psychiatry titles and 11th out of 256 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2015 Impact Factor score for Biological Psychiatry is 11.212.

About Elsevier

Elsevier is a global information analytics company that helps institutions and professionals progress science, advance healthcare and improve performance for the benefit of humanity. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 35,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. http://www.elsevier.com

Media contact

Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
Biol.Psych@UTSouthwestern.edu

Elsevier

Related Schizophrenia Articles:

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.
Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.
Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.
The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.
Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.
Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.
Genetics researchers close in on schizophrenia
Researchers at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University have discovered 50 new gene regions that increase the risk of developing schizophrenia.
Looking for the origins of schizophrenia
Schizophrenia may be related to neurodevelopment changes, including brain's inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ).
Researchers uncover novel mechanism behind schizophrenia
An international team of researchers led by a Case Western Reserve University School of Medicine scientist has uncovered a novel mechanism in which a protein--neuregulin 3--controls how key neurotransmitters are released in the brain during schizophrenia.
A new genetic marker for schizophrenia
Japanese scientists find a rare genetic variant that shows strong association with schizophrenia.
More Schizophrenia News and Schizophrenia Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab