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.