longitudinal mri to assess effect of puberty on subcortical brain development: an observational...

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Poster Abstracts 52 www.thelancet.com Longitudinal MRI to assess effect of puberty on subcortical brain development: an observational study Anne-Lise Goddings, Kathryn Mills, Liv Clasen, Jay Giedd, Russell Viner, Sarah-Jayne Blakemore Abstract Background The human brain undergoes significant change between childhood and adulthood, but little is known about how puberty influences its structural development. To investigate the control mechanisms behind adolescent brain development, we examined how subcortical brain regions change in relation to puberty. Methods We used a longitudinal sample of 711 MRI scans from 275 individuals aged 7–20 years. All participants had at least two scans with recorded Tanner stage (a measure of pubertal status). The MRI scans were processed with surface-based reconstruction software, and volumes were extracted for the a-priori structures of interest: the amygdala, hippocampus, nucleus accumbens (NA), caudate, putamen, and globus pallidus (GP). Mixed-effects modelling established best-fit models of the developmental trajectory of each structure of interest in relation to Tanner stage. Cubic, quadratic, and linear growth models were compared using F tests between models where the highest order variable was significant (p<0·05). Age was added into the Tanner models to see whether the model improved with the combined effects of both variables. Finally, an age-only model was fitted to establish whether this provided a better fit for the data than the models incorporating Tanner stage. This study was approved by the National Institutes for Health’s Institutional Review Board (89-M-0006), and all participants, their guardians, or both gave their written consent to be included in the study at the time of MRI scanning. This study is registered with ClinicalTrials.gov, number NCT00001246. Findings Structural development in all regions of interest was significantly associated with advancing puberty (all p<0·02). For the amygdala, hippocampus, and putamen in both sexes, as well as the caudate in female participants, a combined model (including Tanner stage and age as main effects, and a Tanner stage by age interaction) provided a significantly better fit than did the Tanner-only model (difference between Akaike Information Criterion >5·9). For the NA and GP in both sexes, and for the caudate in male participants, a Tanner by age interaction-only model provided a significant fit to the data, but the model was no improvement over the Tanner stage only model. For the hippocampus and the GP in male participants, age-only models gave a significantly better fit of the data than models incorporating Tanner stage (hippocampus likelihood ratio [LR] test compared with interactive model 4·69, p=0·030; GP LR test compared with interactive model 9·29, p=0·002). Interpretation The developmental trajectories of the subcortical brain structures studied are related to pubertal development during adolescence. This association is likely to reflect the effects of systemic sex hormones on structural brain development. Funding UK Medical Research Council, National Institute of Mental Health. Contributors A-LG conceived the idea for the study. LC and JG collected the data and managed the MRI database. A-LG and KM analysed the data. RV, S-JB, and JG supervised the study including development of the study idea and data analysis. A-LG interpreted the results, supervised by RV, S-JB, and JG. All authors wrote the abstract. Conflicts of interest We declare that we have no conflicts of interest. Published Online February 26, 2014 Poster 91 Institute of Child Health, University College London, London, UK (A-L Goddings MBBS, Prof R Viner MD); Institute of Cognitive Neuroscience, University College London, London, UK (A-L Goddings, K Mills BSc, Prof S-J Blakemore PhD); and Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA (K Mills, L Clasen PhD, J Giedd MD) Correspondence to: Dr Anne-Lise Goddings, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK [email protected]

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Page 1: Longitudinal MRI to assess effect of puberty on subcortical brain development: an observational study

Poster Abstracts

52 www.thelancet.com

Longitudinal MRI to assess eff ect of puberty on subcortical brain development: an observational studyAnne-Lise Goddings, Kathryn Mills, Liv Clasen, Jay Giedd, Russell Viner, Sarah-Jayne Blakemore

Abstract Background The human brain undergoes signifi cant change between childhood and adulthood, but little is known about how puberty infl uences its structural development. To investigate the control mechanisms behind adolescent brain development, we examined how subcortical brain regions change in relation to puberty.

Methods We used a longitudinal sample of 711 MRI scans from 275 individuals aged 7–20 years. All participants had at least two scans with recorded Tanner stage (a measure of pubertal status). The MRI scans were processed with surface-based reconstruction software, and volumes were extracted for the a-priori structures of interest: the amygdala, hippocampus, nucleus accumbens (NA), caudate, putamen, and globus pallidus (GP). Mixed-eff ects modelling established best-fi t models of the developmental trajectory of each structure of interest in relation to Tanner stage. Cubic, quadratic, and linear growth models were compared using F tests between models where the highest order variable was signifi cant (p<0·05). Age was added into the Tanner models to see whether the model improved with the combined eff ects of both variables. Finally, an age-only model was fi tted to establish whether this provided a better fi t for the data than the models incorporating Tanner stage. This study was approved by the National Institutes for Health’s Institutional Review Board (89-M-0006), and all participants, their guardians, or both gave their written consent to be included in the study at the time of MRI scanning. This study is registered with ClinicalTrials.gov, number NCT00001246.

Findings Structural development in all regions of interest was signifi cantly associated with advancing puberty (all p<0·02). For the amygdala, hippocampus, and putamen in both sexes, as well as the caudate in female participants, a combined model (including Tanner stage and age as main eff ects, and a Tanner stage by age interaction) provided a signifi cantly better fi t than did the Tanner-only model (diff erence between Akaike Information Criterion >5·9). For the NA and GP in both sexes, and for the caudate in male participants, a Tanner by age interaction-only model provided a signifi cant fi t to the data, but the model was no improvement over the Tanner stage only model. For the hippocampus and the GP in male participants, age-only models gave a signifi cantly better fi t of the data than models incorporating Tanner stage (hippocampus likelihood ratio [LR] test compared with interactive model 4·69, p=0·030; GP LR test compared with interactive model 9·29, p=0·002).

Interpretation The developmental trajectories of the subcortical brain structures studied are related to pubertal development during adolescence. This association is likely to refl ect the eff ects of systemic sex hormones on structural brain development.

Funding UK Medical Research Council, National Institute of Mental Health.

ContributorsA-LG conceived the idea for the study. LC and JG collected the data and managed the MRI database. A-LG and KM analysed the data. RV, S-JB, and JG supervised the study including development of the study idea and data analysis. A-LG interpreted the results, supervised by RV, S-JB, and JG. All authors wrote the abstract.

Confl icts of interestWe declare that we have no confl icts of interest.

Published OnlineFebruary 26, 2014

Poster 91

Institute of Child Health, University College London,

London, UK (A-L Goddings MBBS,

Prof R Viner MD); Institute of Cognitive Neuroscience, University College London, London, UK (A-L Goddings,

K Mills BSc, Prof S-J Blakemore PhD);

and Child Psychiatry Branch, National Institute of Mental

Health, National Institutes of Health, Bethesda, MD, USA

(K Mills, L Clasen PhD, J Giedd MD)

Correspondence to: Dr Anne-Lise Goddings, UCL

Institute of Child Health, 30 Guilford Street,

London WC1N 1EH, [email protected]