05 October 2013
European College of Neuropsychopharmacology (ECNP)
BARCELONA, SPAIN (7 October 2013) – Improved understanding of the roles of inflammation and oxidative stress in psychiatric disorders has generated new leads in the search for novel therapies. One such investigative compound currently in clinical trials is an amino acid, N-Acetyl Cysteine (NAC), which appears to reduce the core symptoms of bipolar disorder, schizophrenia, depression, autism and cravings in addictions including cocaine, cannabis abuse and cigarette smoking.
At the start of the decade of the brain, in the early 1990s, there was great hope that a flurry of new treatment discoveries would eventuate. In contrast, today, most pharmaceutical companies have a drying psychiatry and neurology pipeline and many have exited the field entirely. “One of the factors has been an over reliance on typical monoamine pathways as targets for drug discovery,” said Professor Michael Berk, Chair in Psychiatry at Deakin University, Geelong, Australia.
Professor Berk pointed out that the situation regarding new drug development for psychiatric problems was best summarised by former National Institute for Mental Health Director, Steven Hyman:
“drug discovery is at a near standstill for treating psychiatric disorders such as schizophrenia, bipolar disorder, depression and common forms of autism.”
Beyond the monoamine-based drugs, neuroscience has elucidated an array of other important pathways that are involved in most major psychiatric disorders, for example schizophrenia and both unipolar and bipolar depression.
According to Professor Berk, there is now an incontrovertible evidence base that these disorders share inflammation and oxidative stress as part of their disease physiology. In addition, associated pathways including reduction in proteins that stimulate neuronal growth (neurotrophins), and increased cell death (apoptosis), as well as energy generation in organelles called mitochondria are intimately involved. “This understanding provides an entirely new set of treatment targets.”
The amino acid, NAC, seems to have multiple effects on all these pathways: it
- boosts glutathione, which is the body’s major antioxidant defence;
- has anti-inflammatory properties;
- enhances levels of nerve cell growth proteins and the growth of new neurons; and
- reduces cell death pathways.
- It also appears to reduce dysfunction of mitochondria.
These molecular effects of NAC have been investigated in a series of clinical trials, which show that NAC reduces the core symptoms of schizophrenia including negative symptoms such as improved apathy, social interaction and motivation.
It also appears to reduce depression in people with bipolar disorder and at this meeting, new data on its role in unipolar major depression was presented. Furthermore, there is intriguing evidence that it reduces cravings in a number of addictions including cocaine, cannabis and cigarette smoking. “Apart from nausea, it appears to be relatively free of problematic side effects,” said Professor Berk.
In addition to NAC, a range of other compounds that target similar pathways, particularly inflammation, seem to have therapeutic potential. These include aspirin, cyclooxygenase (COX) inhibitors, statins, omega-3 fatty acids and even some anti-diabetic agents such as pioglitazone. “Capitalising on our understanding of inflammation and oxidative stress in major psychiatric disorders appears to give us an entirely new range of potential treatments for these common, severe and disabling conditions,” said Professor Berk.
The Journal of the American Medical Association (JAMA) is reporting in a new study that folic acid use during pregnancy may reduce autism risk.
Researchers in Norway reviewed records of 85,000 children and discovered that if mothers were taking folic acid at the time of conception, they were 2.1 times less likely to have children with autism.
February 13, 2013, Vol 309, No. 6 >
Original Contribution | February 13, 2013
Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children
Pål Surén, MD, MPH; Christine Roth, MSc; Michaeline Bresnahan, PhD; Margaretha Haugen, PhD; Mady Hornig, MD; Deborah Hirtz, MD; Kari Kveim Lie, MD; W. Ian Lipkin, MD; Per Magnus, MD, PhD; Ted Reichborn-Kjennerud, MD, PhD; Synnve Schjølberg, MSc; George Davey Smith, MD, DSc; Anne-Siri Øyen, PhD; Ezra Susser, MD, DrPH; Camilla Stoltenberg, MD, PhD
JAMA. 2013;309(6):570-577. doi:10.1001/jama.2012.155925.
Importance Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders.
Objective To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder–not otherwise specified [PDD-NOS]) in children.
Design, Setting, and Patients The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity.
Main Outcome Measure Specialist-confirmed diagnosis of ASDs.
Results At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.
Conclusions and Relevance Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation. http://jama.jamanetwork.com/article.aspx?articleid=1570279
One of the implications of this study is the necessity that women receive adequate prenatal care and women really should have pre-pregnancy counseling and care.
United Health Foundation reports Prenatal Care (1990 – 2011): Percentage of pregnant women receiving adequate prenatal care, as defined by Kessner Index:
Prenatal care is a critical component of health care for pregnant women and a key step towards having a healthy pregnancy and baby. Early prenatal care is especially important because many important developments take place during the first trimester, screenings can identify babies or mothers at risk for complications and health care providers can educate and prepare mothers for pregnancy. Women who receive prenatal care have consistently shown better outcomes than those who did not receive prenatal care. Mothers who do not receive any prenatal care are three times more likely to deliver a low birth weight baby than mothers who received prenatal care, and infant mortality is five times higher. Early prenatal care also allows health care providers to identify and address health conditions and behaviors that may reduce the likelihood of a healthy birth, such as smoking and drug and alcohol abuse. http://www.americashealthrankings.org/All/PrenatalCare/2012
Given this recent study it is imperative that ALL women receive prenatal care particularly poor and those women at risk of difficult pregnancies.
Autism and children of color
Archives of Pediatrics and Adolescent Medicine study: Kids with autism more likely to be bullied
Father’s age may be linked to Autism and Schizophrenia
Chelation treatment for autism might be harmful
Dr. Wilda Reviews © http://drwildareviews.wordpress.com/
By Shirley Wang for the Wall Street Journal
The obesity epidemic may be contributing to the rising number of children diagnosed with autism, according to a study published Monday.
Researchers said mothers who are obese are significantly more likely to have a child with autism or another developmental abnormality. The finding adds to the increasingly complex picture of possible factors that contribute to the disorders.
About half the risk of autism, a condition characterized by poor social skills and repetitive behaviors, is genetic, researchers believe, while the rest stems from factors including older parental age, premature birth or failure to take prenatal vitamins.
The new findings come in the wake of the announcement last month by the U.S. Centers for Disease Control and Prevention that autism-spectrum disorders, as the range of abnormalities is now called, affect one in 88 U.S. children, up from one in 110 in a 2009 report.
The link between obesity and developmental disorders is particularly worrisome because obesity has become so prevalent. About a third of U.S. women of reproductive age are considered obese, the authors said.
A Complex Puzzle
Experts say these factors seem to contribute to autism:
- Obesity among mothers
- Older parental age
- Premature birth/birth complications
- Fewer than 12 months between children
These factors are suspected and are under investigation:
- Environmental toxins
- Diet and other lifestyle factors
- Other existing medical conditions, including viral infections
–Source: WSJ reporting
The new research, published in the journal Pediatrics, studied over 1,000 children aged two to five years old with and without autism or other developmental problems, as well as their mother’s health history.
It showed that compared to non obese mothers, those who were obese before pregnancy had a 60% increase in the likelihood of having a child with autism and a doubling in risk of having a child with another type of cognitive or behavioral delay.
The risk was even more pronounced when mothers who had high blood pressure or diabetes before or during pregnancy were included in the analysis.
The results suggest that obesity and other metabolic conditions are a general risk factor for autism and other developmental disorders, said the researchers from the University of California, Davis and Vanderbilt University.
“The brain is quintessentially susceptible to everything’s that happening in the mother’s body,” said Irva Hertz-Picciotto, senior author of the study and chief of the division of environmental and occupational health in public health sciences at UC Davis.
But she added that “no one factor is going to be responsible for any one child’s case. This is not a ‘blame the mom’ thing.”
Susan Hyman, a developmental behavioral pediatrician at the University of Rochester, found a positive theme in the results. “The statistics on obesity are alarming, but it’s a modifiable risk factor,” she said. Dr. Hyman, who heads the American Academy of Pediatrics’ autism subcommittee, wasn’t involved in the study.
How a mother’s weight or metabolic disorders might contribute to autism or other problems isn’t known. One possibility is that insulin resistance is involved, said Dr. Hertz-Picciotto.
When insulin isn’t made or used properly by the bodyâ€”as can be the case in some obese peopleâ€”it alters how sugar, which serves as energy for the body, is produced and transported to tissues including the brain. Such disruption may have a particularly potent effect on fetal brains, which are known to need a lot of sugar.
The researchers weren’t able to compare mothers who had well-controlled blood sugar to those who didn’t, she said.
Obesity joins a growing list of potential causes of autism. The UC Davis researchers and colleagues had examined other environmental factors, such as pollutants, and last summer published data from the same children in Monday’s study showing the risk of autism doubled if families were living closer to a freeway during the third trimester of pregnancy. Not taking prenatal vitamins and having less than 12 months between kids also have been associated with autism.
Genetics are another contributor. Last week, three independent papers published in the journal Nature found more “highly disruptive” mutationsâ€”ones that caused genes to stop workingâ€”on three genes in children with autism compared to those without, and estimated there could be 500 or more mutations related to autism.
“By and large, the kids with autism didn’t have substantially more mutations but slightly more severe mutations,” said Mark Daly, an author of one of the Nature papers and chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital in Boston.
The papers were seen as a boon to the field because they indicate that a relatively new technique could be used to figure out which genes looked different in children with and without autism. That could provide new avenues for research into the condition, said Matthew State, a professor of child psychiatry, psychiatry and genetics at Yale University who was an author of another of the Nature papers.
Ultimately, both genetic and early environmental factors that are under investigation seem to suggest the period of risk for autism is in the womb, said Bryan King, director of the Seattle Children’s Autism Center, who wasn’t involved in the current study. Together, these “will be very important in focusing the field on what to look for when.”
Write to Shirley S. Wang at email@example.com
When we talk about CSI_Health Crimes, we have just this sort of thing in mind. Read more from Want To Know.info