Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight.

Development of the cerebral cortex may be affected by aberrant white matter development. Preterm birth with very low birth weight (VLBW) has been associated with reduced fractional anisotropy of white matter and changes in cortical thickness and surface area. We use a new methodological approach to combine white and gray matter data and test the hypothesis that white matter injury is primary, and acts as a mediating factor for concomitant gray matter aberrations, in the developing VLBW brain. T1 and dMRI data were obtained from 47 young adults born preterm with VLBW and 73 term-born peers (mean age = 26). Cortical thickness was measured across the cortical mantle and compared between the groups, using the FreeSurfer software suite. White matter pathways were reconstructed with the TRACULA software and projected to their cortical end regions, where cortical thickness was averaged. In the VLBW group, cortical thickness was increased in anteromedial frontal, orbitofrontal, and occipital regions, and fractional anisotropy (FA) was reduced in frontal lobe pathways, indicating compromised white matter integrity. Statistical mediation analyses demonstrated that increased cortical thickness in the frontal regions was mediated by reduced FA in the corpus callosum forceps minor, consistent with the notion that white matter injury can disrupt frontal lobe cortical development. Combining statistical mediation analysis with pathway projection onto the cortical surface offers a powerful novel tool to investigate how cortical regions are differentially affected by white matter injury.

A longitudinal study of associations between psychiatric symptoms and disorders and cerebral gray matter volumes in adolescents born very preterm.

BACKGROUND: Being born preterm with very low birthweight (VLBW ≤ 1500 g) poses a risk for cortical and subcortical gray matter (GM) abnormalities, as well as for having more psychiatric problems during childhood and adolescence than term-born individuals. The aim of this study was to investigate the relationship between cortical and subcortical GM volumes and the course of psychiatric disorders during adolescence in VLBW individuals. METHODS: We followed VLBW individuals and term-born controls (birth weight ≥10th percentile) from 15 (VLBW;controls n = 40;56) to 19 (n = 44;60) years of age. Of these, 30;37 individuals were examined longitudinally. Cortical and subcortical GM volumes were extracted from MRPRAGE images obtained with the same 1.5 T MRI scanner at both time points and analyzed at each time point with the longitudinal stream of the FreeSurfer software package 5.3.0. All participants underwent clinical interviews and were assessed for psychiatric symptoms and diagnosis (Schedule for Affective Disorders and Schizophrenia for School-age Children, Children's Global Assessment Scale, Attention-Deficit/Hyperactivity Disorder Rating Scale-IV). VLBW adolescents were divided into two groups according to diagnostic status from 15 to 19 years of age: persisting/developing psychiatric diagnosis or healthy/becoming healthy. RESULTS: Reduction in subcortical GM volume at 15 and 19 years, not including the thalamus, was limited to VLBW adolescents with persisting/developing diagnosis during adolescence, whereas VLBW adolescents in the healthy/becoming healthy group had similar subcortical GM volumes to controls. Moreover, across the entire VLBW group, poorer psychosocial functioning was predicted by smaller subcortical GM volumes at both time points and with reduced GM volume in the thalamus and the parietal and occipital cortex at 15 years. Inattention problems were predicted by smaller GM volumes in the parietal and occipital cortex. CONCLUSIONS: GM volume reductions in the parietal and occipital cortex as well as smaller thalamic and subcortical GM volumes were associated with the higher rates of psychiatric symptoms found across the entire VLBW group. Significantly smaller subcortical GM volumes in VLBW individuals compared with term-born peers might pose a risk for developing and maintaining psychiatric diagnoses during adolescence. Future research should explore the possible role of reduced cortical and subcortical GM volumes in the pathogenesis of psychiatric illness in VLBW adolescents.

Mental health and cerebellar volume during adolescence in very-low-birth-weight infants: a longitudinal study.

BACKGROUND: Preterm birth at very low birth weight (VLBW) poses a risk for cerebellar abnormalities and increased psychiatric morbidity compared with reference populations. We aimed to study cerebellar volumes (grey and white matter; GM, WM) and mental health in VLBW individuals and controls at 15 and 19 years of age, as well as changes between the two time points. METHODS: Forty VLBW (≤1500 g) and 56 control adolescents were included in the study at 15 years of age, and 44 VLBW and 60 control adolescents at 19 years of age. We had longitudinal data for 30 VLBW participants and for 37 controls. Clinical diagnoses were assessed following the schedule for affective disorders and schizophrenia for school-age children (KSADS). Psychiatric symptoms and function were further investigated with the Achenbach System of Empirically Based Assessment (ASEBA), ADHD Rating Scale-IV and the children's global assessment scale (CGAS). An automatic segmentation of cerebellar GM and WM volumes was performed in FreeSurfer. The MRI scans were obtained on the same 1.5T scanner at both ages. RESULTS: The VLBW group had higher rates of psychiatric disorders at both ages. Cerebellar growth trajectories did not differ between VLBW adolescents and controls, regardless of psychiatric status. However, VLBW adolescents who had a psychiatric diagnosis at both ages or developed a psychiatric disorder from 15 to 19 years had maintained smaller cerebellar WM and GM volumes than controls and also smaller volumes than VLWB adolescents who were or became healthy in this period. Moreover, there were no differences in cerebellar WM and GM volumes between controls and those VLBW who were healthy or became healthy. In the VLBW group, cerebellar WM and GM volumes correlated positively with psycho-social function at both 15 and 19 years of age, and smaller GM volumes were associated with inattention at 15 years. CONCLUSIONS: Smaller cerebellar volume in adolescents born very preterm and with VLBW may be a biomarker of increased risk of psychiatric problems in young adulthood.