gene-environment interactions in neurodevelopmental...

EditorialGene-Environment Interactions inNeurodevelopmental Disorders

Susanna Pietropaolo,1,2 Wim E. Crusio,1,2 and Joram Feldon3

1University of Bordeaux, INCIA, Pessac Cedex, France2CNRS, INCIA, UMR 5287, Pessac Cedex, France3Department of Biology, The Swiss Federal Institute of Technology (ETH), Zurich, Switzerland

Correspondence should be addressed to Susanna Pietropaolo; susanna.pietropaolo@u-bordeaux.fr

Received 8 December 2016; Accepted 12 December 2016; Published 31 January 2017

Copyright © 2017 Susanna Pietropaolo et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Neurodevelopmental disorders (NDDs) include a huge vari-ety of pathologies characterised by varying degrees of intel-lectual disability and behavioural dysfunction. Research dur-ing the last years has underlined the genetic nature of theaetiological factors involved in most NDDs, identifying insome cases (e.g., Fragile X and Rett syndromes) single genemutations as the unique pathological cause, while determin-ing in othersmultiple genetic risk factors (e.g., schizophrenia,autism spectrum disorders (ASDs)).The high interindividualvariability in several key pathological aspects of NDDs,such as the severity of the behavioural symptoms and theage-related progression, has motivated researchers to directtheir attention to environmental factors that may criticallyinfluence the expression of the genetic “determinants” ofthese pathologies. This research has led to several theoreticalmodels describing the relationships between genetic andenvironmental insults in NDDs: these models have in turnemphasised the additive or synergistic interactions betweengenes and environment and increased the interest in betterunderstanding the specific contributions of these interactionsin the aetiopathology of NDDs.

Gene-environment interactions are obviously of rele-vance to most disorders of the nervous system but areespecially important for developmental pathologies, becauseof the considerable plasticity of the developing brain andits critical responsiveness to environmental changes. Indeed,a large body of human and animal data has demonstratedthat environmental stimulation/deprivation can, respectively,ameliorate or exacerbate the symptoms of many NDDs.

Nonetheless, animal studies combining both genetic andenvironmental manipulations are still scarce, at least com-pared to the huge amount of research work that concen-trates only on genetic effects. This special issue aims toattract attention to the importance of gene-environmentinteractions, which so far have often been ignored. Reviewand original research articles are combined to discuss theimpact of the interactions between genetic and environmen-tal interventions in both clinical and preclinical studies. Avariety of NDDs are included, such as ASDs, schizophrenia,Fragile X, Down syndrome, and ADHD, and a multitudeof genetic and environmental manipulations are discussed.Several environmental factors were studied, such as nutri-tional manipulations, immunological changes, environmen-tal enrichment, stress, or social deprivation.These sometimesimplied environmental adversity, but in other cases environ-mental stimulation, possibly supporting nonpharmacologicaltherapies based on sensory-social or nutritional enrichment.

The review by C. Madore et al. investigates the relevanceof nutritional factors in the aetiopathology of neurodevel-opmental disorders. This article is focused in particular onthe role of polyunsaturated fatty acids (PUFAs), becauseof the association between imbalances in PUFA levels andNDDs. Preclinical and clinical data are summarised, high-lighting the anti-inflammatory properties of PUFAs andtheir impact on the microbiota, which is suggested as themain factor potentially linking inflammation, environmentaladversity, and NDDs. P. Moran et al. instead provide a reviewof preclinical studies on gene-environment interactions in

HindawiNeural PlasticityVolume 2017, Article ID 9272804, 2 pageshttps://doi.org/10.1155/2017/9272804

2 Neural Plasticity

schizophrenia using genetic animal models. This reviewdiscusses the synergistic effects of genetic and environmentalrisk factors on the expression of those endophenotypes thatare relevant to schizophrenia, thus supporting the validity ofmultifactorial preclinical models.

The research article by E. Aronoff et al. provides originalclinical data on the therapeutic impact of environmentalenrichment in autistic children. Indeed, a therapy based ondaily sensory enrichment is shown to ameliorate children’sbehavioural problems in multiple domains, including cogni-tive, emotional, social, and sensorial abilities. Interestingly,these effects were largely independent of the subjects’ gender,nationality, or initial severity levels of the pathology. Thearticle by L. Garbugino et al. parallels this human study,providing original data on the effects of early enrichment inan animal model of social dysfunction, the KO mouse forthe 𝜇-opioid receptor gene (Oprm1−/−). Early environmentalstimulation of the highly immature mouse pups using anenrichment protocol providing additional maternal care wasapplied and both short- and long-term behavioural effects ofthis manipulation were detected. The research article by E.Burrows et al. focuses its attention instead on environmentaladversity, evaluating the behavioural effects of social isolationhousing in a mouse model for autism, the Neuroligin-3(NL3) mouse. The data presented here also highlight theimportance of the choice of the procedures for behaviouraltesting in research on genetic models of neurodevelopmentaldisorders, since the effects of the environmental and geneticmanipulations differed depending on the specific social testused.

The review by I. De Toma et al. expands the eval-uation of the effects of gene-environment interactions inNDDs by assessing the role of epigenetic mechanisms in theaetiopathology of these diseases. The link between globaland local epigenetic alterations, such as anomalies in DNAmethylation, histone modifications or chromatin remod-elling, and developmental disorders, is discussed, with a focuson two examples of developmental pathologies characterisedby cognitive impairments, Down syndrome (DS) and FragileX syndrome (FXS). This article also directly describes ther-apeutic approaches using epigenetic drugs that can act ascognitive enhancers in DS and FXS.

In conclusion, this special issue emphasises the impor-tance of continuing and extending neurobehavioural studieson NDDs combining genetic with environmental manipu-lations and suggests that a multifactorial approach is mostlikely to identify novel therapeutic approaches and to advanceour understanding of the aetiopathology of these complexdisorders.

Susanna PietropaoloWim E. CrusioJoram Feldon

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