Abstract
Puberty is a period characterized by major changes in hormone levels, physical appearance, cognition, brain structure and function. The teenage brain undergoes considerable reorganization on a structural and functional level. These changes may be associated with cognitive and social development. Adolescence is also a precarious period, with a several psychiatric
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disorders showing their first symptoms during this period. Determining the process of brain development during puberty is thus not only important for understanding the individual differences in development of teenagers, but can also be important for understanding the causes and consequences of developmental disorders. This dissertation focuses on changes in hormone levels, the relation between hormone levels and brain development, and the development of the white matter network and its relation to intelligence. This was done in a longitudinal study with up to 3 assessments in healthy twins and their older siblings who were recruited from the Netherlands Twin Register (http://www.tweelingenregister.org/). Between ages 9 and 12 years, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone levels in boys and girls showed a 2- to 9-fold increase. LH (in girls) and FSH (in boys) at age 9 were related to secondary sexual characteristics at age 12. Hormone levels and secondary sexual characteristics were mostly under influence of genes. Changes in FSH levels between ages 9 and 12 were positively related to change in gray matter density. At age 12, estradiol was negatively related to gray matter density. These relations were only found in girls and influenced by environmental factors. FA-weighted global efficiency (communication capacity over the entire brain) of the white matter network developed in a non-linear way: an increase from ages 10 to 13 followed by a small decease until around age 20. The increase during early adolescence is partly related to changes in the intelligence quotient (IQ): those participants with most pronounced increases in IQ showed higher increases in global and local FA-weighted efficiency, especially in the frontal and temporal lobes. Local and global efficiency were partly influenced by genetic factors. White matter network efficiency based on streamline count showed increases and decreases in local efficiency, resulting in a net-decrease of streamline count-weighted global efficiency. Changes in local streamline count-weighted efficiency were negatively related to changes in IQ. Clearly, the adolescent streamline count-weighted network reflects a different aspect of the white matter network than the adolescent FA-weighted network. The development of network efficiency was related to IQ. Overall, network efficiency (which can be considered as a measure of communication capacity of the brain) decreased between ages 13-18. However, participants with a high IQ showed stable network efficiency over this age span. The correlation between network efficiency and IQ seems to be a process of adolescent development: whereas there was no correlation between local or global efficiency and IQ at age 10, only a small correlation in a few regions at age 13, there was a brain wide, FDR-corrected significant correlation between local efficiency and IQ at age 18. The correlation between IQ and local FA-efficiency was to a large extent driven by genes that influence both FA-efficiency and IQ.
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