title: White matter development in the early stages of psychosis.
abstract: Schizophrenia has been conceptualized as a disorder of both neurodevelopment and a disorder of connectivity. One important aspect of the neurodevelopmental hypothesis is that schizophrenia is no longer thought to have discrete illness time points, but rather a long trajectory of brain changes, spanning many years, across a series of stages of the disease including the prodrome, first episode, and chronic period. As the disease progresses, there is a complex relationship between age related changes and disease related changes. Therefore, neural changes, and specifically white matter based connectivity changes, in schizophrenia may be best conceptualized based on a lifespan trajectory. In this selective review, we discuss healthy changes in white matter integrity that occur with age, as well as changes that occur across illness stages. We further propose a set of models that might explain lifespan changes in white matter integrity in schizophrenia, with the conclusion that the evidence most strongly supports a pattern of disrupted maturation during adolescence, with the potential for later changes that may be a result of disease neurotoxicity, abnormal or excessive aging effects, as well as medication, cohort or other effects. Thus, when considering white matter integrity in psychosis, it is critical to consider age in addition to other contributing factors including disease specific effects. Discovery of the factors driving healthy white matter development across the lifespan and deviations from the normal developmental trajectory may provide insights relevant to the discovery of early treatment interventions.
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, NorthShore-LIJ Health System, Glen Oaks, NY, United States.
authors.forename: Bart D
authors.initials: BD
authors.lastname: Peters
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, NorthShore-LIJ Health System, Glen Oaks, NY, United States; Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset, NY, United States; Department of Psychiatry, Hofstra NorthShore-LIJ School of Medicine, Hempstead, NY, United States.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Karlsgodt
mesh_terms: D000375:Aging; D018450:Disease Progression; D006801:Humans; D059906:Neuroimaging; D011618:Psychotic Disorders / Q000235:genetics / Q000473:pathology*; D066127:White Matter / Q000254:growth & development* / Q000473:pathology*
keywords: Development; Diffusion tensor imaging; Prodrome; Schizophrenia; White matter