This project builds on our preliminary findings suggesting that, during adolescence, testosterone affects axonal calibre rather than the thickness of myelin sheath and that this effect is moderated by generic variations in the AR receptor. In Aims 1,2 and 4 (see main application), we are taking advantage of the existing longitudinal birth cohort (ALSPAC) that contains a wealth of information about sexual maturation and testosterone levels (at 3 time points), as well as mental health and cognitive abilities, during adolescence. Aim 3 (see main application) will take the first step towards an experimental evaluation of the predicted effects of testosterone on the axon in the rat model.

This is a 5 year programme grant, but ALSPAC costs fall within years 1-4.

Deliverables (ALSPAC)

1. To identify 500 boys with certain variables collected in the past (questionnaire data, or current clinic data) on puberty plus DAWBA, SDQ, DRUGs, PLIKS and bloods for at least 3 time points between ages 9 and 17.

2. To employ a fieldworker(s) to ensure these subjects undergo a structural (and possibly functional) MRI scan at CUBRIC, Cardiff University (under supervision of Prof Derek Jones - subject to a separate arrangement).

3. Saliva samples to be collected for testosterone (added since original proposal - will incur extra costs regarding sample collection, storage, transport and analysis).

4. Administer a computerised questionnaire to the subjects to include CIS-R, PLIKS, substance-use (as in the clinic).

5. Participant recruitment will be reported to the PI so that he may complete the Recruitment Milestone Reporting system in good time. These are due on: April 1st, August 1st, December 1st 2011. The RMR system expects that at least 176 of the 500 subjects will be recruited by 1st April.

6. The statistician will work under the supervision of Beate Glaser and Margaret May on the initial analysis of cohort-based data.

7. The ALSPAC lab technician will support identification, retrieval and preparation of blood and saliva samples for testosterone analyses.

8. The original proposal had participants attending for scans at Bristol Royal Infirmary; however, this has been changed to Cardiff and will increase participant travel considerably.