Perinatal Folic Acid May Protect Against Serious Mental Illness in Young People

MedicalResearch.com Interview with:

Joshua L. Roffman, MD Department of Psychiatry Mass General Hospital

Dr. Roffman

Joshua L. Roffman, MD
Department of Psychiatry
Mass General Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Autism, schizophrenia, and other serious mental illness affecting young people are chronic, debilitating, and incurable at present.  Recent public health studies have associated prenatal exposure to folic acid, a B-vitamin, with reduced subsequent risk of these illnesses.  However, until this point, biological evidence supporting a causal relationship between prenatal folic acid exposure and reduced psychiatric risk has remained elusive.

We leveraged the rollout of government-mandated folic acid fortification of grain products in the U.S. from 1996-98 as a “natural experiment” to determine whether increased prenatal folic acid exposure influenced subsequent brain development.  This intervention, implemented to reduce risk of spina bifida and other disabling neural tube defects in infants, rapidly doubled blood folate levels among women of childbearing age in surveillance studies.

Across two large, independent cohorts of youths age 8 to 18 who received MRI scans, we observed increased cortical thickness, and a delay in age-related cortical thinning, in brain regions associated with schizophrenia risk among individuals who were born during or after the fortification rollout, compared to those born just before it.  Further, delayed cortical thinning also predicted reduced risk of psychosis spectrum symptoms, a finding that suggests biological plausibility in light of previous work demonstrating early and accelerated cortical thinning among school-aged individuals with autism or psychosis.

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Biochemical Test Promises To Aid in Diagnosis of ASD

MedicalResearch.com Interview with:

Juergen Hahn Professor and Department Head Department of Biomedical Engineering Department of Chemical & Biological Engineering Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute

Prof. Hahn

Juergen Hahn,  Professor and Department Head
Department of Biomedical Engineering Department of Chemical & Biological Engineering Center for Biotechnology and Interdisciplinary Studies Rensselaer
Polytechnic Institute 

MedicalResearch.com: What is the background for this study?

Response: Autism Spectrum Disorder (ASD) encompasses a large group of early‐onset developmental disorders that are collectively characterized by deficits in social interaction and communication as well as the expression of restricted, repetitive behaviors and interests. ASD is currently estimated to affect 1 in 59 children in the US. Despite this high prevalence, relatively little is know about the pathophysiology of ASD. The result of this is that no lab test exists for ASD and the diagnosis is based upon observations of the child. The average age of diagnosis is 4 years of age, but it is generally acknowledged that diagnosis at 2 years of age is possible and desirable. Continue reading

Driving Skills May Be Harder to Master with ASD

MedicalResearch.com Interview with:
“Driving” by Martin Alvarez Espinar is licensed under CC BY 2.0Kristina Elise Patrick, Ph.D

Nationwide Children’s Hospital
Columbus, OH 43205

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Many families of young adults with autism spectrum disorder (ASD) are concerned that they may have difficulty acquiring driver’s licenses and driving safely because of symptoms of ASD. However, the ability to drive opens the door to a variety of social, occupational, and educational experiences. We aimed to assess differences in simulated driving behaviors of young adults with ASD and those with typical development and to evaluate whether differences depended on level of driving experience and complexity of the driving task.

On average, young adults with ASD had more difficulty regulating their speed and position within their lane compared with typically developing individuals even on a very basic rural route. After completing the basic route, drivers were required to engage in more complex tasks such as changing the radio or engaging in conversation while driving, driving through a construction zone, and following behind a truck. On complex driving tasks, drivers with ASD who had acquired licensure drove similarly to typically developing drivers who had acquired licensure. However, novice drivers with ASD had more difficulty than typically developing drivers regulating their speed and position within the lane.

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Food Allergies More Common in Children With ASD

MedicalResearch.com Interview with:

Wei Bao, MD, PhD Assistant Professor, Epidemiology College of Public Health University of Iowa

Dr. Wei Bao

Wei Bao, MD, PhD
Assistant Professor, Epidemiology
College of Public Health
University of Iowa

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies indicated a possible link between immunologic dysfunction and autism. The current study, based on nationally representative large-scale surveys, showed that food allergy, respiratory allergy, and skin allergy, all relevant to immunological dysfunction, were associated with autism spectrum disorder among US children.

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No Link Found Between Autism and Maternal Fish Ingested During Pregnancy

MedicalResearch.com Interview with:
“Fish” by Dhruvaraj S is licensed under CC BY 2.0Dr Caroline M Taylor
Wellcome Trust Research Fellow
Centre for Child and Adolescent Health
Bristol Medical School, University of Bristol
Oakfield House, Oakfield Grove, Bristol

MedicalResearch.com: What is the background for this study?

Response: Mercury is a toxic metal that is widespread in the environment. In pregnancy, mercury in the mother’ bloodstream is transferred through the placenta to the fetus, where is can affect development of the nervous system. Mercury from vaccines has been the focus of attention particularly in regard to a link with autism in children. However, the amount of mercury used in the vaccines is small in comparison with mercury from the diet and atmospheric pollution, and in the EU at least, childhood vaccines no longer contain this preservative. The fear that mercury is linked to autism has persisted, despite increasing evidence that this is not the case.

The aim of our study was to look at mercury from the diet rather than vaccines – specifically from fish – in pregnant women. We measured the women’s mercury levels in their blood and asked them about how much fish they ate. We then followed up their children for 9 years and recorded how many of them had autism diagnosed within that time. We also measured how many of them had autist traits by measuring their social and communication difficulties.  The data were part of the Children of the 90s study (Avon Longitudinal Study of Parents and Children – ALSPAC), which is based in Bristol, UK.

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Umbilical Cord Blood Stem Cells May Improve Symptoms in Children with Autism

MedicalResearch.com Interview with:

Michael G. Chez, M.D. Director of Pediatric Neurology Sutter Memorial Hospital Director of the Pediatric Epilepsy and Autism Programs Sutter Neuroscience Group 

Dr. Michael Chez

Michael G. Chez, M.D.
Director of Pediatric Neurology Sutter Memorial Hospital
Director of the Pediatric Epilepsy and Autism Programs
Sutter Neuroscience Group 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The study looked at possible use of autologous cord blood as a source of stem cells in patients with autism. The patients had to have fairly good genetic screening per protocol and had confirmation of autism to participate.

The use of cord blood was a pilot cross over double blind study with hypothesis that a post natal factor or immune dysregulation may add to the autism clinical phenotype.

Cord blood ( the baby’s own from birth) is a safe source of mixed stem cell types and should be safe from rejection or autoimmune reaction in theory.

Infusion /placebo or placebo/infusion was randomized and observed and tested every 3 months with switch to other wing of treatment at 0 and 6 months. Total observation was over 1 year.

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Subtle Motor Biomarker May Be Essential Feature of Autism Spectrum Disorder

Indiana University graduate student Di Wu poses for a portrait in Swain Hall on Friday, Dec. 22, 2017.

Di Wu credit: James Brosher

MedicalResearch.com Interview with:
Di Wu, Msc
PhD candidate at Indiana University
Graduate Research Assistant
Department of Physics
Indiana University Bloomington
Linked-in: www.linkedin.com/in/di-wu-3a197373 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Current clinical diagnosis and evaluations of Autism Spectrum Disorder (ASD). has remained subjective in nature. There is a need to have objective assessments for the disorder. We discovered in this study an important motion feature that was unknown before. This feature provides a clear screening of ASD. It gave a remarkable quantitative connection between the way children with ASD move and their psychiatric scores, like the IQ score and the Vineland Adaptive Behavior Scale. This connection we captured suggests that the motor feature may be an essential core feature characterizing ASD deficits, as well as neurodevelopment in general.

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Brain Signals Reflect Social Anxiety and Performance Fears in ASD

MedicalResearch.com Interview with:

Tamara Rosen

Tamara Rosen

Tamara Rosen
Graduate student in Clinical Psychology
Stony Brook University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Approximately 40 percent of youth with autism spectrum disorder (ASD) are diagnosed with a co-occurring anxiety disorder.  Social anxiety is a common presenting problem for these youth.

Youth with ASD and increased social anxiety have heightened threat sensitivity, particularly in relation to performance fears, as measured by a brain signal response called the error-related negativity (ERN), which measures response to errors. The threat sensitivity-performance fears association remained even after controlling for anxiety symptoms other than social fearfulness.

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Lack of Folic Acid Supplements During Pregnancy Linked With Increased Autism Risk in Children Exposed to Seizure Drugs In Utero

MedicalResearch.com Interview with:

Dr. Marte Bjørk, MD PhD Department of Clinical Medicine University of Bergen, Department of Neurology Haukeland University Hospital Bergen, Norway

Dr. Marte Bjørk

Dr. Marte Bjørk, MD PhD
Department of Clinical Medicine
University of Bergen,
Department of Neurology
Haukeland University Hospital
Bergen, Norway

MedicalResearch.com: What is the background for this study?

Response: In utero antiepileptic drug exposure are associated with neurodevelopmental problems in the child. We looked into if maternal folate during pregnancy could reduce the risk of autistic traits in children of women in need of antiepileptic drugs in pregnancy. The rationale for the hypothesis that folate could be beneficial, was that many antiepileptic drugs interact with folate metabolism. Folic acid supplement use is also associated with slightly reduced risk of autism in children of women from the general population.

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Mechanism Identified Linking ASD and Intellectual Disability, Opening Door To Development of Treatment Options

MedicalResearch.com Interview with:

Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience  Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960

Dr-Woo-Yang Kim

Woo-Yang Kim, Ph.D
Associate Professor
Department of Developmental Neuroscience
Munroe-Meyer Institute
University of Nebraska Medical Center
Omaha, NE 68198-5960

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions.

Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown.

Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes.

Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability.

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Multivitamins in Pregnancy May Be Associated With Lower Autism Risk

MedicalResearch.com Interview with:
Elizabeth DeVilbiss, PhD MPH
Dornsife School of Public Health
Drexel University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Unfortunately, not much is known about how diet during pregnancy affects autism risk.  There have been studies in recent years about varied aspects of diet during pregnancy and autism risk involving multivitamins, iron, folic acid, vitamin D, and more, but the evidence is still inconclusive.

After adjusting for several potentially influencing factors in both mothers and children, we found that multivitamin use, with or without additional iron and/or folic acid, was associated with a lower likelihood of child autism spectrum disorder with intellectual disability relative to mothers who did not use folic acid, iron, and multivitamins.

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Autism Spectrum Disorder Found To Be Highly Heritable

MedicalResearch.com Interview with:

Sven Sandin, PhD Assistant Professor Department of Psychiatry Icahn School of Medicine at Mount Sinai New York, NY 10029

D. Sandin

Sven Sandin, PhD Assistant Professor
Department of Psychiatry
Icahn School of Medicine at Mount Sinai
New York, NY 10029 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2014, we estimated the heritability of autism to be approximately 50%. Motivating us then was the lack of studies in autism heritability using population based and the findings from a twin-study in California finding the heritability to be substantially lower than the 80-90% estimated in previous studies. Since then continued efforts working with the questions on heritability and environmental factors for autism we found differences between different methods and different samples. When we went back to our previous data we found the heritability of autism to be higher than previously estimated. We found that our previous result was due to a methodological artifact where the adjustment for differences in follow-up used in that manuscript underestimated the heritability. Using methods used in other heritability studies the heritability is now estimated to 84%. Importantly, as previously concluded, there is no support for any ‘shared environmental factors’ in the etiology of autism, e.g. environmental factors shared between two siblings.

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Folic Acid May Reduce Risk of Autism Associated With Pesticide Exposure During Pregnancy

MedicalResearch.com Interview with:

Rebecca J. Schmidt, M.S., Ph.D.  Assistant Professor, Public Health Sciences UC Davis California

Dr. Schmidt

Rebecca J. Schmidt, M.S., Ph.D. 
Assistant Professor, Public Health Sciences
UC Davis California

MedicalResearch.com: What is the background for this study?

Response: Maternal folic acid taken near conception has been linked to reduced risk for autism in the child in previous studies.

Separate studies show that exposure to pesticides during pregnancy is associated with increased risk for autism.

Animal studies demonstrate that folic acid and other B-vitamins can attenuate effects of certain environmental contaminants, including pesticides.

This case-control study examined combined maternal folic acid and pesticide exposures in relation to autism in the child.

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Association of Brain White Matter Structure With Autism Spectrum Disorder and ADHD

MedicalResearch.com Interview with:

Dr. Adriana Di Martino, MD Associate Professor, Department of Child and Adolescent Psychiatry NYU Langone Health

Dr. Di Martino

Dr. Adriana Di Martino, MD
Associate Professor, Department of Child and Adolescent Psychiatry
NYU Langone Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: While there has been an increased awareness of the co-occurrence of symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) in children with a primary diagnosis of ASD, only recently has there been an appreciation that a substantial proportion of children with ADHD may also have ASD traits. These symptom domains overlap pose a challenge for accurate recognition and targeted treatments, yet their underlying mechanisms have been unknown.

With more traditional diagnostic group comparisons we detected a significant influence of ASD on white matter organization, but our analyses of the severity of symptoms across individuals revealed an association between autistic traits and white matter organization, regardless of the individual’s diagnosis. These findings were mostly centered around the corpus callosum, a structure that enables communication between the left and right cerebral hemispheres.

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Study Finds Diet Not Connected to GI Problems in Children With Autism

MedicalResearch.com Interview with:

Bradley James Ferguson, PhD University of Missouri School of Medicine

Dr. Ferguson

Bradley James Ferguson, PhD
University of Missouri School of Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many individuals with autism spectrum disorder (ASD) have gastrointestinal problems, such as constipation, irritable bowel syndrome and abdominal pain, but the cause of these GI issues is not currently known. Previous research from our laboratory showed a significant positive relationship between cortisol levels and GI problems, especially for constipation. However, it is possible that other factors such as diet may affect GI functioning, especially since many children have altered diets. This study examined 32 different nutrients in the children’s diets, as assessed by a food frequency questionnaire that assessed the participant’s diet over the past month, and how each nutrient was related to upper and lower GI tract symptom scores over the past month created from the Questionnaire on Pediatric Gastrointestinal Symptoms – Rome III. The results showed no significant relationships between any of the nutrients and GI symptoms, suggesting that diet was not associated with GI symptoms in this sample.

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MRI At Six Months Can Predict Which High Risk Babies Will Develop Autism

MedicalResearch.com Interview with:

Joseph Piven, MD The Thomas E. Castelloe Distinguished Professor of Psychiatry UNC School of Medicine Director of the Carolina Institute for Developmental Disabilities Co-senior author of the study

Dr. Piven

Joseph Piven, MD
The Thomas E. Castelloe Distinguished Professor of Psychiatry
UNC School of Medicine
Director of the Carolina Institute for Developmental Disabilities
Co-senior author of the study

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Babies with older siblings with autism are at an increased risk (20%) of getting autism over the general population (1%).  Infants who later are diagnosed with autism don’t have any of the stigmata of autism in the first year of life. The symptoms of autism unfold in the first and particularly in the second year of life and beyond.

We have evidence to support the idea that behavioral symptoms of autism arise from changes in the brain that occur very early in life. So we have employed MRI and computer analyses to study those early brain changes and abnormalities in infancy to see if early brain changes at 6 months of age can predict whether babies at high-risk of developing autism will indeed develop the condition at age two.

For this particular study, we used data from MRIs of six-month olds to show the pattern of synchronization or connection across brain regions throughout the brain and then predict which babies at high familial risk of developing autism would be most likely to be diagnosed with the condition at age two.

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Baby Teeth Can Expose Toxic Levels of Minerals Associated With Autism

MedicalResearch.com Interview with:

Manish Arora, PhD Associate Professor Environmental Medicine & Public Health Icahn School of Medicine at Mount Sinai

Dr. Arora

Manish Arora, PhD
Associate Professor
Environmental Medicine & Public Health
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Autism has both genetic and environmental risk factors. Our aim was to study if exposure to toxic metals, such as lead, or disruptions in the uptake of essential nutrient elements such as manganese or zinc would be related to autism risk. Furthermore, we were interested in not only understanding how much exposure had taken place but also which developmental periods were associated with increased susceptibility to autism risk.

Researchers suspect that the risk factors for autism start early in life, even prenatally, but measuring in utero exposures is technically very challenging. We used a newly developed technique that uses lasers to map growth rings in baby teeth (like growth rings in trees) to reconstruct the history of toxic metal and essential nutrient uptake. We applied this technology in samples collected from twins, including twins who were discordant for autism. This allowed us to have some control over genetic factors.

We found that twins with autism had higher levels of lead in their teeth compared to their unaffected twin siblings. They also had lower levels of zinc and manganese. The lower uptake of zinc was restricted to approximately 10 weeks before birth to a few weeks after birth, indicating that as a critical developmental period.

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Gene Dosage at 22q11.2 Helps Determine Schizophrenia vs Autism Brain Differences

MedicalResearch.com Interview with:

Carrie Bearden, Ph.D. Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology Semel Institute for Neuroscience and Human Behavior University of California, Los Angeles

Dr. Bearden

Carrie Bearden, Ph.D.
Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology
Semel Institute for Neuroscience and Human Behavior
University of California, Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population.

Thus, we became interested in trying to understand whether there were differences in brain development that might predispose to one condition vs. the other.

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Metformin Reverses Some Autism Symptoms In Animal Model

MedicalResearch.com Interview with:
Ilse Gantois, PhD

Research Associate
Dr. Nahum Sonenberg’s laboratory
Department of Biochemistry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by cognitive impairment and affects 1 in 4000 males and 1 in 6000 females. About 60% of persons with Fragile X also have autism spectrum disorder. FXS is caused by absence of Fragile X protein (FMRP), which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rapamycin complex 1) signaling. We show that treatment with metformin, the most widely used FDA-approved antidiabetic drug, suppresses translation by inhibiting the ERK pathway, and alleviates a variety of behavioural deficits, including impaired social interaction and excessive grooming. In addition, metformin also reversed defects in dendritic spine morphogenesis and synaptic transmission.
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Study Finds No Link To Autism, ADHD In Offspring From Antidepressant Use In Pregnancy

MedicalResearch.com Interview with:

Simone Vigod, MD, MSc, FRCPC Psychiatrist and Lead, Reproductive Life Stages Program Women’s Mental Health Program Women’s College Hospital Toronto, ON

Dr. Vigod

Simone Vigod, MD, MSc, FRCPC
Psychiatrist and Lead, Reproductive Life Stages Program
Women’s Mental Health Program
Women’s College Hospital
Toronto, ON

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Depression is one of the most common problems that can complicate a pregnancy. Untreated, or incompletely treated, it can be associated with significant harm to mother and child. While psychotherapies alone may be effective for women with mild (or even moderate) severity symptoms, sometimes antidepressant medication is required. In these cases, the benefits of treatment must be weighed against potential risks. Previous research suggested that there may be an increased risk for autism in children exposed to antidepressant medication during pregnancy. However, previous studies were limited in their ability to account for other potential causes of autism in their analyses. In our study, we used several different strategies to try to compare children whose pregnancy exposures were very similar, except for exposure to an antidepressant.

The main finding was that after using these strategies, there was no longer a statistically significant association between in-utero antidepressant exposure and autism.

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