Abstractin English, Spanish, French

This article describes the history of the diagnostic class of neurodevelopmental disorders (NDDs) up to DSM-5.

We further analyze how the development of genetics will transform the classification and diagnosis of NDDs. In DSM-5, NDDs include intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD).

Physicians in German-, French- and English-speaking countries (eg, Weikard, Georget, Esquirol, Down, Asperger, and Kanner) contributed to the phenomenological definitions of these disorders throughout the 18th and 20th centuries.

These diagnostic categories show considerable comorbidity and phenotypic overlap.

NDDs are one of the chapters of psychiatric nosology most likely to benefit from the approach advocated by the National Institute of Mental Health's Research Domain Criteria project.

Genetic research supports the hypothesis that ID, ASD, ADHD, schizophrenia, and bipolar disorder lie on a neurodevelopmental continuum.

The identification of recurrently observed copy number variants and disruptive gene variants in ASD (eg, CDH8, 16p11.2, SCN2A) led to the adoption of the genotype-first approach to characterize individuals at the etiological level. .

Abstract

Events in fetal life impact long-term health outcomes. The placenta is the first organ to form and is the site of juxtaposition between the maternal and fetal circulations.

Most diseases of pregnancy are caused by, impact, or are reflected in the placenta.

The purpose of this review is to describe the main inflammatory processes in the placenta, discuss their immunology, and relate their short- and long-term disease associations.

Acute placental inflammation (API), including maternal and fetal inflammatory responses corresponds to the clinical diagnosis of chorioamnionitis and is associated with respiratory and neurodevelopmental diseases.

The chronic placental inflammatory pathologies (CPI), include chronic villitis of unknown etiology, chronic deciduitis, chronic chorionitis, eosinophilic T-cell vasculitis, and chronic histiocytic intervillositis.

These diseases are less-well studied, but have complex immunology and show mechanistic impacts on the fetal immune system.

Overall, much work remains to be done in describing the long-term impacts of placental inflammation on offspring health.

Abstract

Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon.

Here, we leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis and stress signaling.

We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an interleukin-17a-dependent manner, which reduced global mRNA translation and altered nascent proteome synthesis.

Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as increased cortical neural activity in MIA male offspring.

Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.

New insights into the detection, pathophysiology and treatment of inflammation-induced injury in the immature brain

The immature brain is especially vulnerable to inflammatory factors, before, during and after birth. This publication presents new insights into the detection, pathophysiology and treatment of inflammation-induced injury in the developing brain from both clinical and basic science perspectives.

Cellular mechanisms that lead to perinatal brain injury are presented, with specific emphasis on inflammation, brain development and potential treatment strategies. In particular, studies report on inflammatory pathways involved in perinatal brain injury, including caspases, STAT3, toll-like receptors and oxidative stress. Some data demonstrate how different inflammatory cell types may contribute to the injury, such as microglia and mast cells, and how peripheral organs can influence the cerebral inflammatory response.

Further, new developments in neuroprotective therapies using human amnion epithelial cells to reduce inflammation-induced brain damage in the fetus are described.

This publication is recommended to both clinicians and basic scientists who are interested in the developing nervous system, its vulnerability to inflammation and the short- and long-term consequences for neurologic development.

Past research has suggested that both genes and prenatal insults -- such as exposure to alcohol and nicotine -- can increase the risk of attention-deficit/hyperactivity disorder (ADHD).

But the identified increases in risk have been very modest.

Now, scientists has found that when those factors are studied together, risk of a severe type of ADHD greatly increases. .   .  .

"But when we looked at the effect of maternal smoking in children with one of our candidate genes, we saw a three-fold increase in risk, and in children with both genes whose mothers smoked during pregnancy, we saw a nine-fold increase," says senior investigator Richard D. Todd, M.D., Ph.D., the Blanche F. Ittleson Professor and director of the Division of Child Psychiatry at Washington University.

"Our findings begin to offer an explanation for the modest effects we've seen when looking at genes or environmental variables one at a time. It appears it's really the interaction of genes and environmental factors that predisposes a child to problems with ADHD."

Anxiety is also elevated in autism and this heightened state of distress occurs across the full age range. Research has shown, for example, that children on the autism spectrum are more likely to suffer from anxiety with close to 40 percent having at least one diagnosable anxiety disorder (Van Steenel, Bögels, & Perrin, 2011).

Given that both anxiety and GI problems are high in autism, it’s interesting to ponder whether or not there is a link between the two.

Research suggests that there is. Mazurek and colleagues (2013), for example, found that autistic children with GI conditions had higher rates of both anxiety and sensory over-responsivity.

There may be common underlying mechanisms that are unique to autism that influence the association between anxiety and GI problems. Some areas of the GI system which have been found to be impacted in autism include:

• Increased intestinal permeability
• Altered intestinal microbiota
• Altered Serotonin metabolism

However, it is important to note that the association between emotional distress and GI symptoms also exists for those who are not autistic.

There is an increasingly growing body of literature demonstrating a relationship between emotional distress and GI symptoms for the population at large.

In some ways, this is not surprising given the multiple ways in which the GI tract and nervous system interact.

The interactions between the GI tract and the nervous system are so close that the gut is sometimes referred to as “the Second Brain”.

Writing in the Journal of Attention Disorders, researchers note that ADHD symptoms are associated with stress, especially for those adults who primarily have the inattentive presentation. Chronic stress makes symptoms worse, and even causes chemical and architectural changes to the brain, affecting the brain’s ability to function.

In Nature Neuroscience, researchers note that stress affects the prefrontal cortex, the same location of the brain affected by ADHD. There, stress reduces neuronal firing and impairs cognitive abilities.

Dr. Murray says that research has shown repeatedly that stress causes changes to the brain. There is a decrease in the executive functioning abilities of the brain, often seen in the person’s ability to organize information and activities, and to manage emotions.

“What we can see over time, especially when stress is at the level we could consider toxic or chronic—or traumatic—you can see some effects on the brain,” she says.

“It’s both brain structure, and size of some specific sections, along with brain function, as related to some of the brain chemicals.

There is a reduced cognitive capacity for making decisions, goal-setting and problem-solving—the things we think of as related to cognitive self-regulation.”

Stress and anxiety increase when we’re in situations over which we have little or no control (a car going off the road, tripping on the stairs, reading in public).

All people, young and old, can experience overwhelming stress and exhibit signs of anxiety, but children, adolescents, and adults with dyslexia are particularly vulnerable.

That’s because many individuals do not fully understand the nature of their learning disability, and as a result, tend to blame themselves for their own difficulties.

Years of self-doubt and self recrimination may erode a person’s self-esteem, making them less able to tolerate the challenges of school, work, or social interactions and more stressed and anxious.


Many individuals with dyslexia have experienced years of frustration and limited success, despite countless hours spent in special programs or working with specialists.

Their progress may have been agonizingly slow and frustrating, rendering them emotionally fragile and vulnerable.

Some have been subjected to excessive pressure to succeed (or excel) without the proper support or training.

Others have been continuously compared to siblings, classmates, or co-workers, making them embarrassed, cautious, and defensive.