Schizophrenia delays and alters maturation of the brain in adolescence

Abstract

Early-onset schizophrenia appears to be clinically more severe than the adult-onset form of the disease. In a previous study, we showed that anatomically related grey and white matter abnormalities found in adolescents patients were larger and more widespread than what had been reported in the literature on adult schizophrenia. Particularly, we found novel structural abnormalities in the primary sensorimotor and premotor systems. Here, we tested alternative hypotheses: either this striking sensorimotor-related pattern is an artefact due to a better sensitivity of the methods, or apparent greater structural abnormalities in the early-onset population are specifically associated with earlier disease onset. Then, if we were to find such characteristic structural pattern, we would test whether these anatomical abnormalities would remain static or, conversely, show dynamic changes in the still developing brain. To address these questions, we combined a cross-sectional study of brain structure for adolescent-onset patients (n = 25) and adult-onset patients (n = 35) and respective matched healthy subjects with a longitudinal study of adolescent-onset patients (n = 12, representative subset of the cross-sectional group) and matched healthy controls for >2 years. Looking at differences between adolescent and adult patients' grey matter volume and white matter microstructure abnormalities, we first confirmed the specificity (especially in motor-related areas) and the greater severity of structural abnormalities in the adolescent patients. Closer examination revealed, however, that such greater anomalies seemed to arise because adolescent patients fail to follow the same developmental time course as the healthy control group. Longitudinal analysis of a representative subset of the adolescent patient and matched healthy populations corroborated the delayed and altered maturation in both grey and white matters. Structural abnormalities specific to adolescent-onset schizophrenia in the sensori-motor cortices and corticospinal tract were less marked or even disappeared within the longitudinal period of observation, grey matter abnormalities in adolescent patients evolving towards the adult-onset pattern as defined by recent meta-analyses of adult schizophrenia. Combining cross-sectional adolescent and adult datasets with longitudinal adolescent dataset allowed us to find a unique, abnormal trajectory of grey matter maturation regardless of the age at onset of symptoms and of disease duration, with a lower and later peak than for healthy subjects. Taken together, these results suggest common aetiological mechanisms for adolescent- and adult-onset schizophrenia with an altered neurodevelopmental time course in the schizophrenic patients that is particularly salient in adolescence.

A common brain network links development, aging, and vulnerability to disease

“…It should be noted that relatively late maturation in the lateral part of the primary motor cortex and small part of lingual gyrus is also seen during healthy adolescence and in adolescent-onset schizophrenia (38,39). We have previously found that adolescentonset schizophrenia exhibits an altered maturational pattern compared with matched healthy adolescents (38), with differences in M1, SMA, and lingual gyrus initially present at 16 y, and fading away 2.5 y later.…”

“…We have previously found that adolescentonset schizophrenia exhibits an altered maturational pattern compared with matched healthy adolescents (38), with differences in M1, SMA, and lingual gyrus initially present at 16 y, and fading away 2.5 y later. One difference between the inverted-U network of IC4 and the spatial pattern of adolescent-onset schizophrenia was the absence of medial temporal lobe abnormalities in the latter case (Figs.…”

“…There is mounting evidence that the pattern of various brain disorders can be explained to some extent by observing the healthy brain. Deviations from normal trajectories of brain maturation have been identified in developmental disorders (38,48), while some neurodegenerative disorders seem to progress within specific healthy brain networks (23,49). One recent study has also shown that data-driven decomposition of white matter tractograms in healthy young subjects recapitulates the pattern of abnormalities in dementia (50).…”

Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture

“…We adopted a longitudinal diffusion processing scheme similar to previous analyses (Douaud et al, 2009;Engvig et al, 2012). First, the initial alignment between brain-extracted images at baseline and post-treatment time points were conducted using FMRIB's Linear Image Registration Tool (FLIRT, degrees of freedom = 6), and both images were resampled to a common space halfway between the two (Jenkinson et al, 2002), which only requires a single registration per volume and thus minimizes registration bias towards one of the two time points.…”

Reactivity of perineuronal astrocytes in the prefrontal cortex in schizophrenia: an ultrastructural morphometric study

“…Шизофрения, начавшаяся в раннем возрасте, является наиболее тяжелой клинической фор-мой болезни [57]. У больных с ранним началом шизофре-нии (в подростковом возрасте) методом диффузионно-тензорной томографии показаны задержка развития и со-зревания мозга и более выраженные изменения в сером и белом веществе по сравнению с началом болезни в зрелом возрасте [58], в частности нарушения сложности в форми-ровании борозд и извилин коры больших полушарий. У подростков при первом эпизоде психоза снижено со-держание N-acetyl aspartate в ПФК, отражающее сниже-ние функционального состояния нейронов, в том числе по данным магнитно-резонансной спектроскопии [59].…”