Developmental timing and critical windows for the treatment of psychiatric disorders

Abstract

There is a growing understanding that pathological genetic variation and environmental insults during sensitive periods in brain development have long-term consequences on brain function, which range from learning disabilities to complex psychiatric disorders such as schizophrenia. Furthermore, recent experiments in animal models suggest that therapeutic interventions during sensitive periods, typically before the onset of clear neurological and behavioral symptoms, might prevent or ameliorate the development of specific pathologies. These studies suggest that understanding the dynamic nature of the pathophysiological mechanisms underlying psychiatric disorders is crucial for the development of effective therapies. In this Perspective, I explore the emerging concept of developmental windows in psychiatric disorders, their relevance for understanding disease progression and their potential for the design of new therapies. The limitations and caveats of early interventions in psychiatric disorders are also discussed in this context.

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Figure 1: Age of diagnosis for several neuropsychiatric disorders in relation to key processes in human neurodevelopment.
Figure 2: Brain regions and cell types affected in schizophrenia.
Figure 3: Milestones in the development of neural networks in the mouse neocortex.
Figure 4: Maturation of PV+ interneurons and critical-period plasticity.

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Acknowledgements

I apologize for not citing all relevant references, owing to space limitations. I thank B. Rico and members of the Marín lab for valuable discussions and their critical reading of this manuscript. The European Research Council (ERC-2011-AdG 293683), Wellcome Trust (103714MA), Simons Foundation Autism Research Initiative (SFARI 239766OM) and De Spoelberch Foundation support work on this topic in my laboratory. O.M. is a Wellcome Trust Investigator.

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Correspondence to Oscar Marín.

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Marín, O. Developmental timing and critical windows for the treatment of psychiatric disorders. Nat Med 22, 1229–1238 (2016). https://doi.org/10.1038/nm.4225

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