White matter development in adolescence: the influence of puberty and implications for affective disorders

Abstract

There have been rapid advances in understanding a broad range of changes in brain structure and function during adolescence, and a growing interest in identifying which of these neurodevelopmental changes are directly linked with pubertal maturation—at least in part because of their potential to provide insights into the numerous emotional and behavioral health problems that emerge during this developmental period. This review focuses on what is known about the influence of puberty on white matter development in adolescence.We focus on white matter because of its role in providing the structural architectural organization of the brain and as a structural correlate of communication within complex neural systems. We begin with a review of studies that report sex differences or sex by age interactions in white matter development as these findings can provide, although indirectly,information relevant to puberty-related changes. Studies are also critically reviewed based on methodological procedures used to assess pubertal maturation and relations with white matter changes. Findings are discussed in light of their implications for the development of neural systems underlying the regulation of emotion and behavior and how alterations in the development of these systems may mediate risk for affective disorders in vulnerable adolescents.

Keywords: affective disorders; diffusion tensor imaging; puberty; white matter development; white matter volume.

Fig. 1

Regions with a significant sex–age interaction on FA (blue = boys > girls, yellow-red = girls > boys) in a cohort of 105 children ages 5–18 years. Slice location (L-R; Talairach coordinate system) given at bottom of each frame. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)

Fig. 2

Luteinizing hormone (LH) and changes in white matter density in 9-year-old children. Specifically, the images on the left (i) depicts positive phenotypic associations between LH level and regional white matter density in 104 9-year-old twins. (A) Left cingulum, (B) bilateral middle temporal gyrus, (C) splenium of the corpus callosum. Displayed are z-values. The critical z-value was 3.39 (corrected for multiple comparisons according to the false discovery rate, a = .05). The scatterplot on the right (ii) depicts a phenotypic association between LH level and white matter density in the left anterior cingulum. Depicted are LH levels versus white matter densities in the left anterior cingulum (Talairach x, y and z coordinates −13, 23 and 36). The phenotypic correlation coefficient is 0.44 (95% CI = 0.26–0.58). The LH-values are log-transformed and ranged between −2.25 and −.78, corresponding to LH values ranging between 0.056 and 0.167 U/l (divided by creatinine-level). The actual raw uncorrected LH values range between 0.1 and 1.1 U/l.

Fig. 3

FA reductions in healthy adolescents at high familial risk for unipolar depression compared to healthy controls. Specifically, the significant clusters obtained from voxel-wise comparisons between control and high-risk groups. Green color indicates white matter skeletons, and red color shows clusters with significant FA reduction in the high-risk group (p < 0.001). Underlying gray scale images are the averaged FA maps, depicting different tracts. The left, middle, and right columns of each panel show the images of axial, coronal, and sagittal views, respectively. White arrows indicate clusters of the specified white matter tracts in the left cerebral hemisphere if multiple clusters are shown in the image. FA, fractional anisotropy; CG-L, left cingulate, SLF-L, left superior longitudinal fasciculus; SCC, splenium of the corpus callosum; UNC-IFO-L, left uncinate-inferior fronto-occipital fasciculus. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)