Gene-Environment Interactions in Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) include a huge variety of pathologies characterised by varying degrees of intellectual disability and behavioural dysfunction. Research during the last years has underlined the genetic nature of the aetiological factors involved in most NDDs, identifying in some cases (e.g., Fragile X and Rett syndromes) single gene mutations as the unique pathological cause, while determining in others multiple genetic risk factors (e.g., schizophrenia, autism spectrum disorders (ASDs)). The high interindividual variability in several key pathological aspects of NDDs, such as the severity of the behavioural symptoms and the age-related progression, has motivated researchers to direct their attention to environmental factors that may critically influence the expression of the genetic " determinants " of these pathologies. This research has led to several theoretical models describing the relationships between genetic and environmental insults in NDDs: these models have in turn emphasised the additive or synergistic interactions between genes and environment and increased the interest in better understanding the specific contributions of these interactions in the aetiopathology of NDDs. Gene-environment interactions are obviously of relevance to most disorders of the nervous system but are especially important for developmental pathologies, because of the considerable plasticity of the developing brain and its critical responsiveness to environmental changes. Indeed, a large body of human and animal data has demonstrated that environmental stimulation/deprivation can, respectively, ameliorate or exacerbate the symptoms of many NDDs. Nonetheless, animal studies combining both genetic and environmental manipulations are still scarce, at least compared to the huge amount of research work that concentrates only on genetic effects. This special issue aims to attract attention to the importance of gene-environment interactions, which so far have often been ignored. Review and original research articles are combined to discuss the impact of the interactions between genetic and environmental interventions in both clinical and preclinical studies. A variety of NDDs are included, such as ASDs, schizophrenia, Fragile X, Down syndrome, and ADHD, and a multitude of genetic and environmental manipulations are discussed. Several environmental factors were studied, such as nutritional manipulations, immunological changes, environmental enrichment, stress, or social deprivation. These sometimes implied environmental adversity, but in other cases environmental stimulation, possibly supporting nonpharmacological therapies based on sensory-social or nutritional enrichment. The review by C. Madore et al. investigates the relevance of nutritional factors in the aetiopathology of neurodevel-opmental disorders. This article is focused in particular on the role of polyunsaturated fatty acids (PUFAs), because of …