Breaking News
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Experts address sleep disorders following traumatic brain injury
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
December 9, 2018 - Feds say heroin, fentanyl remain biggest drug threat to US
December 9, 2018 - Eliminating microglia can reverse some aspects of stress sensitization, study shows
December 9, 2018 - New genetic insight could help treat rare debilitating heart and lung condition
December 9, 2018 - MiRagen Therapeutics Announces Final Safety, Biodistribution and Clinical Efficacy Data From Phase 1 Cobomarsen Clinical Trial in Patients With Mycosis Fungoides
December 9, 2018 - Work with your doctor to weigh pros, cons of treatment options for hyperthyroidism
December 9, 2018 - CWRU researcher secures $14.6 million funding for genetic study into Alzheimer’s disease
December 9, 2018 - High intensity statin treatment and adherence could save more lives
December 9, 2018 - Surgery patients use only 1/4 of prescribed opioids, and prescription size matters
December 9, 2018 - AXT offers Phi Optics upgrade to QPI systems for inverted light microscopes
December 9, 2018 - New booklet could help improve conditions of young pupils with albinism
December 9, 2018 - Few Physicians Work in Practices That Use Telemedicine
December 9, 2018 - Older Adults and Oral Health
December 9, 2018 - Health utility values improve after septorhinoplasty
December 9, 2018 - New EU-funded project provides insight into how the brain develops
December 9, 2018 - Expanded use of tele-emergency services can help strengthen rural hospitals
December 9, 2018 - Infections in the Young May Be Tied to Risk for Mental Illness: Study
December 9, 2018 - Profile: Native Hawaiians and Pacific Islanders
December 9, 2018 - Snoring poses greater cardiac risk to women
Gene-brain association occurs differently in toddlers with autism and poor language development

Gene-brain association occurs differently in toddlers with autism and poor language development

image_pdfDownload PDFimage_print

An international team of scientists, led by researchers at the University of Cyprus and University of California San Diego School of Medicine, have identified a previously unknown, large-scale association between molecular gene expression activity in blood leukocyte cells and altered neural responses to speech in toddlers with autism as measured with functional magnetic resonance imaging (fMRI).

The findings were published online November 26 in the journal Nature Neuroscience.

The large-scale gene-brain association occurs differently in toddlers diagnosed with autism spectrum disorder (ASD) and who have poor language development compared to toddlers with ASD and good language development or typically developing toddlers. This large-scale association involved a very large number of genes, many of which are commonly expressed in many tissues, including the brain and leukocytes, a type of blood cell.

“Many of the genes involved are known from other work to be involved in prenatal brain development are human-specific, are linked to vocal learning, and importantly, have been directly implicated in ASD by other genetic and postmortem studies,” said first author Michael Lombardo, PhD, assistant professor of psychology at the University of Cyprus. “The findings show that different molecular biological mechanisms underpin functional brain development in a subtype of ASD toddlers with poor language outcome, and this biology is present before such outcomes are known.”

Accordingly, say the authors, the work suggests that functional neuroimaging measures and gene expression levels in blood leukocyte cells may offer a novel in vivo way to identify brain-relevant molecular mechanisms in ASD.

“They also show how using peripheral blood samples could help inform our understanding of how brain development dynamically changes across the lifespan,” said co-senior author Eric Courchesne, PhD, professor of neurosciences at UC San Diego School of Medicine. “For example, the methodology behind this work can be utilized in the future to monitor how the biology of a patient, at molecular and neural systems levels, responds to treatment or changes over the lifespan across different outcomes.”

Early language development in autism is highly variable, noted the authors. “Some toddlers with autism are minimally verbal, while at the other extreme, many individuals develop language like typically developing toddlers,” said Lombardo. “An important and long-standing question has been whether these very different language profiles in autism are subtype distinctions that point to different biological underpinnings.”

“We need to better understand the biological underpinnings of different early language development in autism because early language ability is one of the most important predictors of early intervention response and later-life outcomes,” said Courchesne. “If we can understand that biology, this may have high impact in future work examining how to best facilitate change to the biology that can then substantially improve longer term outcomes for patients.”

At UC San Diego School of Medicine, a research team led by Courchesne and co-senior author Karen Pierce, PhD, professor of neuroscience and co-director with Courchesne of the UC San Diego Autism Center of Excellence, collected blood samples from 118 toddlers, average age 29 months or just under 2-and-a-half years old, and measured transcriptional activity of all protein coding genes in the genome.

The UC San Diego team additionally collected fMRI data during natural sleep from toddlers while they were passively exposed to speech stimuli. Using behavioral clinical assessment data collected repeatedly each year from one to four years of age, Pierce divided the toddlers with autism into subtypes that showed poor or good language outcome by three to four years of age.

Lombardo then used advanced biostatistics analyses to cluster genes into highly correlated “gene modules,” assessing how activity in the modules related to whole-brain neural response to speech. The researchers found that module activity linked to neural responses to speech was widespread across the genome, encompassing several thousand genes working in coordinated fashion.

The finding, said authors, was highly linked to in vivo fMRI response in living patients and is a methodological advance that could help improve how clinicians assess which individuals will respond to different kinds of treatment.

“One of the biggest challenges in advancing understanding of ASD has been the absence of a method to identify what gene activity differences underlie the initial brain differences and the clinical symptoms in living toddlers with ASD,” said Courchesne. “This is because the living toddler’s brain is inaccessible to the direct measurement of gene activity. As such, gene activity differences underlying emerging brain dysfunction and clinical symptoms has remained completely unknown — until now.

“Our method takes advantage of the fact that a large number of ASD-relevant and prenatal brain-relevant genes and gene networks broadly express in easily accessible non-brain tissues, such as leukocytes as well as in brain. By carefully analyzing such early age gene activity, it’s possible to advance understanding of this key biology in living toddlers with ASD. This unique method not only can have a huge impact on understanding the molecular bases of ASD, but also how to monitor changes in the biology as a function of early intervention. We think this method for linking molecular mechanisms in available peripheral samples, such as blood, with in vivo measures of the brain using neuroimaging helps us substantially.”

Courchesne said researchers plan to extend their work in clinically relevant directions, such as monitoring treatment response in ASD subtypes and potentially leverage information derived from gene expression, fMRI and clinical measures to develop tools that can better predict language outcomes for toddlers with ASD at very early ages.

Source:

https://health.ucsd.edu/news/releases/Pages/2018-11-18-Brain-Responses-to-Language-in-Toddlers-with-Autism-Linked-to-Altered-Gene-Expression.aspx?_ga=2.10539005.810214612.1543303859-2119186239.1515157559

Tagged with:

About author

Related Articles