Search bioRxiv⌕ Search

Biology subjects

Norbom, L. B.

Publications and source records attributed to Norbom, L. B..

2 recordsLinked to original sources
bioRxiv2018

Probing developmental patterns of intracortical myelination using gray/white matter contrast and associations with cognitive abilities and psychopathology in youth

BackgroundCerebral myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. Differential myelination between intracortical and subjacent white matter can be approximated using signal intensities in T1-weighted magnetic resonance images (MRI).\n\nMethodsTo test the sensitivity of gray/white matter contrast (GWC) to age and individual differences in psychopathology and general cognitive ability in youth (8-23 years), we formed data-driven psychopathology and cognitive components using a large population-based sample, the Philadelphia Neurodevelopmental Cohort (PNC) (n=6487, 52% females). We then tested for associations with regional GWC defined by an independent component analysis (ICA) in a subsample with available MRI data (n=1467, 53% females).\n\nResultsThe analyses revealed a global GWC component, which showed an age-related decrease from late childhood and across adolescence. In addition, we found regional anatomically meaningful components with differential age associations explaining variance beyond the global component. When accounting for age and sex, both higher symptom levels of anxiety or prodromal psychosis and lower cognitive ability were associated with higher GWC in insula and cingulate cortices and with lower GWC in pre- and postcentral cortices. We also found several additional regional associations with anxiety, prodromal psychosis and cognitive ability.\n\nConclusionIndependent modes of GWC variation are sensitive to global and regional brain developmental processes, possibly related to differences between intracortical and subjacent white matter myelination, and individual differences in regional GWC are associated with both mental health and general cognitive functioning.

neuroscience↗
bioRxiv2018

Cerebellar grey matter volume in adolescence is associated with prodromal psychotic symptoms and norm-violating behavior

ImportanceAccumulating evidence supports cerebellar involvement in mental disorders such as schizophrenia, bipolar disorder, depression, anxiety disorders and attention-deficit hyperactivity disorder. However, little is known about cerebellar involvement in the developmental stages of these disorders. In particular, whether cerebellar morphology is associated with early expression of specific symptom domains remains unclear.\n\nObjectiveTo determine the robustness and specificity of associations between cerebellar morphology, general cognitive function, general psychopathology and sub-clinical psychiatric symptom domains in adolescence.\n\nDesign, setting and participantsAssessment of parametric structure-function associations between MR-based brain morphometric features and data-driven cognitive and clinical phenotypes in the Philadelphia Neurodevelopmental Cohort (N=1401, age-range: 8 - 23).\n\nMain outcomes and measuresRobust prediction of cognitive and clinical symptom domain scores from cerebellar, subcortical and cerebro-cortical brain features using machine learning with 10-fold internal cross-validation and permutation-based statistical inference.\n\nResultsCerebellar morphology predicted both general cognitive function and general psychopathology (mean Pearson correlation coefficients between predicted and observed values: r = .20 and r = .13, respectively; corrected p-values < .0009). Analyses of specific sub-clinical symptom domains revealed significant associations with rates of norm-violating behavior (r = .17; p < .0009), prodromal psychotic symptoms (r = .12; p < .0009) and anxiety symptoms (r = .09; p =.0117). In contrast, we observed no significant associations between cerebellar features and the severity of attention deficits, depressive, manic or obsessive-compulsive symptoms (all rs =< .03, all ps => .1). Associations with norm-violating behavior and prodromal psychotic symptoms were stronger for the cerebellum than for subcortical and cerebro-cortical regions, while anxiety and general cognitive function were related to more global brain morphology patterns. The association between cerebellar volume and prodromal psychotic symptoms, and to a lesser extent norm violating behavior, remained significant when adjusting for potentially confounding factors such as general cognitive function, general psychopathology, parental education level and use of psychoactive substances.\n\nConclusions and relevanceThe robust associations with sub-clinical psychiatric symptoms in the age range when these typically emerge highlight the cerebellum as a key brain structure in the development of severe mental disorders.\n\nKey pointsO_ST_ABSQuestionsC_ST_ABSIs cerebellar morphology associated with sub-clinical psychiatric symptoms in adolescence? Do such associations show symptom domain specificity or do they rather constitute a marker of general psychopathology?\n\nFindingsMachine learning utilizing cerebellar morphology features significantly predicted the severity of prodromal psychotic symptoms, norm-violating behavior and anxiety, but not attention deficits, depressive, manic or obsessive-compulsive sub-clinical symptoms. Associations with prodromal psychotic symptoms were stronger for the cerebellum than for cerebral subcortical and cerebro-cortical regions, and remained significant when adjusting for several potentially confounding factors.\n\nMeaningThe cerebellum appears to play a key role in the development of severe mental illness.

neuroscience↗