Is there such a thing as 'pure' autism?

Genetic analysis from a new study in Biological Psychiatry says no

2015-04-20

(Press-News.org) Philadelphia, PA, April 20, 2015 - The search for genes that contribute to the risk for autism has made tremendous strides over the past 3 years. As this field has advanced, investigators have wondered whether the diversity of clinical features across patients with autism reflects heterogeneous sources of genetic risk.

If so, it was reasoned, then selecting a group of patients with very similar clinical features might result in a "purer", i.e., more genetically homogenous, group of patients, making it easier to find autism-related genes.

Results from a new study published in the current issue of Biological Psychiatry now cast the validity of this view into doubt.

A large group of collaborating scientists used data from the Simons Simplex Collection, a project that extensively characterized 2576 autism simplex families, the largest such cohort amassed to date and for which the data is now available in a permanent repository.

The availability of this vast collection allowed the researchers to create phenotypic subgroups. In addition to the whole sample, this resulted in 11 subgroups of patients with similar diagnostic, IQ and symptom profiles. They then analyzed the genotypic data in an attempt to discover common genetic variants that confer risk for autism spectrum disorder.

Their results did not identify any genome-wide significant associations in the overall sample or in the phenotypic subgroups. This means that the extreme clinical variability observed among patients with autism spectrum disorder does not closely reflect common genetic variation.

"This study did not provide good evidence that selecting patients with similar symptoms results in a greater ability to find autism genes," said Dr. John Krystal, Editor of Biological Psychiatry. "This might suggest that some of the clinical variability in autism arises from causes other than genetic vulnerability, such as epigenetic changes or other responses to the environment."

It is important to note that these results are in alignment with the recent major change to autism's diagnostic classification in the Diagnostic and Statistical Manual of Mental Disorders. In its 5th revision, several separate disorders, which included autism and Asperger's disorder, were grouped into a single category termed autism spectrum disorder. That decision was based on growing evidence that the previously-distinct disorders actually reflected a continuum of severity of the same condition.

"We hope our study is a step towards a new paradigm for studies involving the relationship between psychiatric phenotypes and genotypes. Most previous studies have sought to refine or narrow phenotypic variation irrespective of its impact on genetic variation, with the expectation that such refinement will improve detection of genetic variation increasing risk for a disorder," explained first author Dr. Pauline Chaste from Centre Hospitalier Sainte Anne in France.

"Our results motivate another route, one targeting the genetic structure of traits and, for multiple traits, their genetic correlations," Chaste added. "For autism, one important implication of our results is that our colleagues have done a very good job in first defining it; however, to make better headway on discovering genetic variation underlying risk, we believe refining phenotypes in light of their impact on genetic architecture will be essential."

INFORMATION:

The article is "A Genome-wide Association Study of Autism Using the Simons Simplex Collection: Does Reducing Phenotypic Heterogeneity in Autism Increase Genetic Homogeneity?" by Pauline Chaste, Lambertus Klei, Stephan J. Sanders, Vanessa Hus, Michael T. Murtha, Jennifer K. Lowe, A. Jeremy Willsey, Daniel Moreno-De-Luca, Timothy W. Yu, Eric Fombonne, Daniel Geschwind, Dorothy E. Grice, David H. Ledbetter, Shrikant M. Mane, Donna M. Martin, Eric M. Morrow, Christopher A. Walsh, James S. Sutcliffe, Christa Lese Martin, Arthur L. Beaudet, Catherine Lord, Matthew W. State, Edwin H. Cook Jr., and Bernie Devlin (doi: 10.1016/j.biopsych.2014.09.017). The article appears in Biological Psychiatry, Volume 77, Issue 9 (May 1, 2015), published by Elsevier.

Notes for editors Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Dr. Pauline Chaste at +33-1-45-65-61-05 or p.chaste@ch-sainte-anne.fr.

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 135 Psychiatry titles and 14th out of 251 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2013 Impact Factor score for Biological Psychiatry is 9.472.

Biological Psychiatry Journal: http://www.biologicalpsychiatryjournal.com/

About Elsevier Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions -- among them ScienceDirect, Scopus, Elsevier Research Intelligence and ClinicalKey -- and publishes over 2,500 journals, including The Lancet and Cell, and more than 33,000 book titles, including a number of iconic reference works. Elsevier is part of RELX Group plc, a world-leading provider of information solutions for professional customers across industries. http://www.elsevier.com

ELSE PRESS RELEASES FROM THIS DATE:

LGBT-competent physicians are scarce at US academic medical practices, UCLA study finds

2015-04-20

Research has shown that, for a number of reasons, lesbian, gay, bisexual and transgender people are significantly more likely than heterosexuals to avoid or delay medical care. For instance, LGBT individuals who are between the ages of 18 and 44 and single are less likely than heterosexuals to have the money or insurance for care, and even partnered gays and lesbians are twice as likely to be uninsured. The fear of stigma and homophobia can also keep LGBT people from seeking care. And many are afraid to disclose their sexual or gender identity to their physicians, which ...

A common nerve protein elevated in aggressive neuroblastomas

2015-04-20

PHILADELPHIA - A protein produced by nerve cells appears to be elevated in the blood of those with an aggressive form of neuroblastoma. The finding, presented today at the American Association for Cancer Research 2015 Annual Meeting in Philadelphia, could potentially lead to a prognostic test for the disease or be used to monitor its progress. Neuroblastoma is a pediatric cancer with varying types, ranging from spontaneously regressing to untreatable fatal tumors. Consequently, treatment strategies vary significantly between patients, encompassing different approaches ...

Overnight fasting may reduce breast cancer risk in women

2015-04-20

A decrease in the amount of time spent eating and an increase in overnight fasting reduces glucose levels and may reduce the risk of breast cancer among women, report University of California, San Diego School of Medicine researchers in the journal Cancer Epidemiology, Biomarkers & Prevention. The findings were presented at the American Association of Cancer Research's annual meeting in Philadelphia. "Increasing the duration of overnight fasting could be a novel strategy to reduce the risk of developing breast cancer," said Catherine Marinac, UC San Diego doctoral candidate ...

Immune therapy tested in study of women with triple-negative breast cancer

2015-04-20

Early data in a preliminary human study show that an experimental immune system drug is generally safe and well tolerated in women with metastatic, triple-negative breast cancer, a persistently difficult form of the disease to treat. Results of the early-phase clinical trial of the therapy, called MPDL3280A, which aims to restore the immune system's ability to recognize and attack cancer cells, are expected to be presented at the American Association for Cancer Research's 2015 Annual Meeting in Philadelphia from April 18-22. Triple-negative breast cancer cells lack expression ...

3-T MRI advancing on ultrasound for imaging fetal abnormalities

2015-04-20

TORONTO, April 20, 2015--Although ultrasound remains the primary imaging modality used in prenatal imaging, fetal MRI is playing an increasing role in further evaluation of fetuses suspected of congenital anomalies. As 3-T MRI scanners become more common due to their improved image signal-to-noise ratio and anatomical detail, the benefits of 3-T MRI must be weighed against potential risks to the fetus that may result from the higher field strength. "MRI is playing an increasingly important role in the assessment of complex prenatal disease," said Kathleen E. Carey, MD, ...

Advanced techniques improve success rate of IVC filter removal to more than 98 percent

2015-04-20

TORONTO, April 20, 2015--The design of inferior vena cava (IVC) filters for pulmonary embolism prophylaxis, once used almost exclusively for permanent implantation, has progressed to retrievable designs. However, complications can create scenarios in which the routine filter retrieval is either extremely difficult or impossible. The use of advanced retrieval techniques, such as loop-snare, "sandwich," stiff wire or balloon realignment, forceps retrieval and excimer laser sheath can raise the overall success rate above 98%. "Implementation of IVC filters is increasing ...

Thin-cut coronary calcium quantification: Advantages compared with standard 3 mm slices

2015-04-20

TORONTO, April 20, 2015--Research comparing the accuracy of three MDCT slice thicknesses has found that 3-mm slices underestimated coronary artery calcium (CAC) scores at every level of calcification. The inaccuracies were caused by partial volume averaging errors. "Our analysis proved this concept and showed that CAC can be more accurately measured with 0.5 or 1 mm using isotropic data acquisition obtained by a volume scanner at identical radiation dose ," said Farhood Saremi, MD, University of Southern California. "Coronary artery calcium can be more accurately measured ...

Ultrasound/MRI fusion biopsy detects more sonographically occult prostate cancers

2015-04-20

TORONTO, April 20, 2015--Research conducted at the State University of New York Upstate Medical University has found that multiparametric MRI and subsequent fusion of MR images with ultrasound enables a targeted biopsy of high-suspicion foci with increased diagnostic accuracy of prostate cancer over established methods. For patients on active surveillance for low-risk cancer, multiparametric MRI can better characterize the prostate gland and find occult foci of higher grade disease. "The need to differentiate a clinically significant cancer from indolent cancers is ...

Computational fluid dynamics in coronary plaques predict coronary artery disease

2015-04-20

TORONTO, April 20, 2015-- Computational fluid dynamics (CFD) simulation based on 3D luminal reconstructions of the coronary artery tree can be used to analyze local flow fields and flow profiling resulting from changes in coronary artery geometry. Research conducted at Curtin University in Perth, Australia, used the technique to identify risk factors for development and progression of coronary artery disease. Both idealized and realistic coronary models were successfully generated using CFD simulations of hemodynamic flow. Results showed a direct correlation between left ...

Dual-energy CT imaging improves pancreatic cancer assessment

2015-04-20

TORONTO, April 20, 2015-- Dual-energy CT (DECT) has several potential applications in the detection, characterization, staging, and follow-up of pancreatic cancer patients, according to a new study conducted at Johns Hopkins University. "DECT imaging is a promising technique, and it has the potential to improve lesion detection and characterization beyond levels available with single-energy CT imaging," said Satomi Kawamoto, MD, associate professor of radiology and radiological science at Hopkins. Several studies have shown that DE CT can help assessment of pancreatic ...

Is there such a thing as 'pure' autism?

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: