N-Acetyl Cysteine Offers Therapeutic Alternative In Psychiatric Disorders

05 October 2013

European College of Neuropsychopharmacology (ECNP)

 

Edvard Munch Painting 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.

 

 

Autism Linked To Environmental Factors

New Studies of Air Pollution, Pesticides and Iron Bolster Evidence Tying Developmental Disorder to Influences in Womb

SAN SEBASTIÁN, Spain—Researchers at an international conference on autism Friday presented three new studies lending strength to the notion that environmental influences before birth play a role in the risk for the condition.

Air Pollution Over Los Angeles SkylineAgence France Presse/Getty Images

In one study, pregnant women who were exposed to certain levels of air pollution were at increased risk of having a child with autism. Another presentation suggested that iron supplements before and early in pregnancy may lower the risk, and a third suggested some association between use of various household insecticides and a higher risk of autism.

A new study finds that a pregnant woman’s exposure to certain levels of air pollution may contribute to an increased risk of autism in her child. Here, an early morning photo shows poor air quality in Los Angeles.

The causes of autism, a developmental disorder that involves social-skill problems, among other symptoms, aren’t well understood but are thought to be multifaceted. Genetics likely account for about 35% to 60% of the risk, many researchers say. But some experts and parents believe that nutrition and other environmental factors may also play a role, especially as the rate of autism in the U.S. appears to have climbed sharply over the past decade.

The new studies showed only associations and couldn’t prove causality, and each factor itself likely accounts for a small portion of the risk for autism, researchers say. But the results, taken together with previous work—showing an association with factors like the flu and the use of certain medicines in pregnant women, for instance—provide more evidence that environmental factors affecting the womb, including what we eat and where we live, are meaningful in terms of autism risk.

“The exciting thing about looking at environment, or environment and genes in conjunction with each other, is this provides the possibility of intervention,” said Irva Hertz-Picciotto, an environmental epidemiologist at the University of California, Davis, who presented the study on insecticides.

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Speaking in a packed auditorium at the International Society for Autism Research annual conference here, Marc Weisskopf of the Harvard School of Public Health presented results from a large national study, known as the Nurses’ Health Study II. The research suggested that a mother’s exposure to high levels of certain types of air pollutants, such as metals and diesel particles, increased the risk of autism by an average of 30% to 50%, compared with women who were exposed to the lowest levels.

Dr. Weisskopf and his colleagues examined levels of some particles and pollutants that the U.S. Environmental Protection Agency has measured and studied across the country in the locations where the approximately 330 women from the study who reported having a child with autism lived. They compared the levels with 22,000 women who didn’t have a child with autism, focusing on 14 pollutants that had been previously reported in the literature as possibly linked to autism.

The results mimicked those of previously published work on traffic pollution and autism risk in California. The consistency of findings across studies “certainly makes me start to feel much more certain that we’re on a path to finding something environmental that’s playing a role here,” said Dr. Weisskopf, a professor of environmental health and epidemiology. “At this stage it does seem there’s something related to air pollution.”

Children Autism Rates 2000-2008 Chart

Data from another large study, known as the Charge study, also presented Friday, found for the first time that mothers who reported that they had taken iron supplements just before or early on in pregnancy had a 40% decrease in associated risk of having a child with autism, an effect similar in magnitude to that of folic-acid supplementation and its reduction of certain birth defects, said Rebecca Schmidt, a professor of public-health sciences UC Davis.

Her team compared the mothers of 510 kids with an autism-spectrum disorder to mothers of 341 kids without autism. Mothers completed a phone survey that included questions on many types of environmental exposures, including supplements like prenatal vitamins, multivitamins and nutrient-specific vitamins, cereal and protein bars, which are often fortified with iron and other nutrients. They weren’t asked about other dietary sources of iron, such as red meat and leafy green vegetables.

Dr. Schmidt cautioned that women shouldn’t boost iron intake without getting their levels checked by a doctor, because too much iron can lead to toxicity. “It’s much easier to change your diet or supplemental intake than it is to change your exposure to many other toxins,” said Dr. Schmidt.

In a separate analysis of the Charge data, UC Davis researchers also found a relationship between exposure to some insecticides in the household, such as bug foggers, and features of autism, but more research is needed to understand why there is a potential link, said Dr. Hertz-Picciotto.

Write to Shirley S. Wang at shirley.wang@wsj.com

A version of this article appeared May 4, 2013, on page A3 in the U.S. edition of The Wall Street Journal, with the headline: Autism Linked to Environmental Factors.

Autism: Peer-Reviewed Analysis

 

Folic Acid At Conception Reduces Autism Risk

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.

pregant women, folic acid reduces autism risk

Citation:

 

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.

Article

Figures

Tables

References

 

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[1]. 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[2].  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.

 

Related:

 

Autism and children of color                                               

http://drwilda.com/tag/children-of-color-with-autism/

 

Archives of Pediatrics and Adolescent Medicine study: Kids with autism more likely to be bullied                                  

http://drwilda.com/2012/09/06/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

http://drwilda.com/2012/08/26/fathers-age-may-be-linked-to-autism-and-schizophrenia/

 

Chelation treatment for autism might be harmful 

http://drwilda.com/2012/12/02/chelation-treatment-for-autism-might-be-harmful/

 

Dr. Wilda Reviews ©                                                http://drwildareviews.wordpress.com/

 

Autism Link To Obesity In Mothers

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.

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“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 body—as can be the case in some obese people—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” mutations—ones that caused genes to stop working—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 shirley.wang@wsj.com

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