Developmental trajectories of gyrification and sulcal morphometrics in children and adolescents at high familial risk for bipolar disorder or schizophrenia

Abstract

Offspring of parents with severe mental illness are at increased risk of developing psychopathology. Identifying endophenotypic markers in high-familial-risk individuals can aid in early detection and inform development of prevention strategies. Using generalized additive mixed models, we compared age trajectories of gyrification index (GI) and sulcal morphometric measures (i.e., sulcal depth, length and width) between individuals at familial risk for bipolar disorder or schizophrenia and controls. 300 T1-weighted MRI scans were obtained of 187 individuals (53 % female, age range: 8-23 years) at familial risk for bipolar disorder (n = 80, n families=55) or schizophrenia (n = 53, n families=36) and controls (n = 54, n families=33). 113 individuals underwent two scans. Globally, GI, sulcal depth and sulcal length decreased significantly with age, and sulcal width increased significantly with age in a (near-)linear manner. There were no differences between groups in age trajectories or mean values of gyrification or any of the sulcal measures. These findings suggest that, on average, young individuals at familial risk for bipolar disorder or schizophrenia have preserved developmental patterns of gyrification and sulcal morphometrics during childhood and adolescence.

Keywords: Bipolar disorder; Gyrification; High familial risk; Longitudinal; Offspring; Schizophrenia.

Graphical abstract

Fig. 1

Schematic representation of the gyrification index and sulcal morphometrics used in the current study. The gyrification index (GI) is defined as the cortical surface area (inner contour, solid line) divided by the hull surface area (outer contour, dashed line). Sulcal depth is calculated as the geodesic distance between the sulcal base and the hull, averaged across all points along the median sulcal surface. Sulcal length is determined on the hull and defined as the summed distance of the intersections between the median sulcal surfaces and the hull. Sulcal width is calculated as the width of the CSF in the sulcus: it is the volume of cerebrospinal fluid in the sulcus, divided by the surface of the skeleton mesh. Adapted with permission from “Longitudinal Allometry of Sulcal Morphology in Health and Schizophrenia” by Janssen et al., (2022), The Journal of Neuroscience, 42(18), p. 3706.

Fig. 2

Age trajectories (in years) of total brain gyrification index, average sulcal depth, total sulcal length and average sulcal width. Generalized additive mixed model (k = 4) fits and 2-standard-error bands are presented on top of the raw data. The gyrification index, average sulcal depth and total sulcal length decreased and average sulcal width increased significantly with age in controls (all p’s < 0.001). After multiple comparison correction, there were no significant differences in the age trajectories between the three groups. Note that the fits may be slightly vertically shifted compared to the raw data points due to age being centered in the generalized additive mixed model, as this influences the intercept some.

Fig. 3

Age trajectories (in years) of gyrification of the bilateral frontal, parietal, temporal and occipital lobes and cingulate cortex. Generalized additive mixed model (k = 4) fits and 2-standard-error bands are presented on top of the raw data. There was a significant effect of age in controls in all bilateral lobes (all p’s ≤ 0.001), where the gyrification index decreased with age in all lobes. After multiple comparison correction, there were no significant differences in age trajectories between the three groups. Note that the fits may be slightly vertically shifted compared to the raw data points due to age being centered in the generalized additive mixed model, as this influences the intercept some. The highlighted lobes in the right-most figures are presented on the left hemisphere purely for visualization purposes.

Fig. 4

Brain color maps of Robust Effect Size Index (RESI) estimates for the effect of age in controls and of each age*group pairwise comparison in the linear mixed-effects model analyses on lobar gyrification and hemispheric average sulcal depth, total sulcal length and average sulcal width. Note that while the RESI itself is an index, a positive or negative sign is assigned based on the direction of the effect. For the effect sizes of the group comparisons, red reflects regions where the first group has a lower increase or steeper decrease than the second group, and blue-grey reflects regions where the first group has a higher increase or less steep decrease than the second group.

Fig. 5

Brain color maps of Robust Effect Size Index (RESI) estimates for each pairwise group comparison (the group variable) in the linear mixed-effects model analyses on lobar gyrification and hemispheric average sulcal depth, total sulcal length and average sulcal width. Note that while the RESI itself is an index, a positive or negative sign is assigned based on the direction of the effect. Red reflects regions where the first group has lower values than the second group, and blue-grey reflects regions where the first group has higher values than the second group.