Abstract
It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18–65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18–65 year age range.
Highlights
It is essential to characterize the pathogenesis of schizophrenia (SZ) and evolution of the illness during the lifespan to develop future therapeutic strategies and improve disease outcomes.According to the classical neurodevelopmental hypothesis of SZ pathogenesis, genetic and environmental factors can interfere with the development of the central nervous system, leading to permanent errors in the organization of axonal connections or other complex morphological characteristics of the brain as cell patterning or brain asymmetry [1,2,3,4]
In the voxelwise analysis of the age-related changes of white matter (WM) FA in SZ and healthy control (HC), a negative correlation between FA and age was found for both diagnostic groups in the entire skeleton
The assumption of homogeneity of regression slopes was fulfilled and a main effect of the diagnosis emerged in a bilateral portion of the WM skeleton mainly located in the corona radiata, corpus callosum, thalamic radiations and external capsule
Summary
It is essential to characterize the pathogenesis of schizophrenia (SZ) and evolution of the illness during the lifespan to develop future therapeutic strategies and improve disease outcomes.According to the classical neurodevelopmental hypothesis of SZ pathogenesis, genetic and environmental factors can interfere with the development of the central nervous system, leading to permanent errors in the organization of axonal connections or other complex morphological characteristics of the brain as cell patterning or brain asymmetry [1,2,3,4]. We can look at age-related trajectories followed by diffusion tensor imaging (DTI) parameters. These microstructural indexes are reliable and sensitive tools for detecting subtle, but critical, structural abnormalities even where macrostructural volumetric impairments cannot be observed. DTI provides significant descriptions of age-related changes in neural development It helps to explain mechanisms of physiological and pathological aging [8,9,10,11,12] as well as different neuropsychiatric conditions [13,14,15] and it allows to map brain plasticity, even in elderly subjects [16]. Only the concurrent investigation of interplaying diffusivity- and anisotropy-related parameters can help clarifying brain microstructural features in SZ and other neuropsychiatric disorders
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