B2158 - Excessive drinking and alcohol related harms in Adulthood ALSPAC at 24 - 06/02/2014

B number: 
B2158
Principal applicant name: 
Prof Matt Hickman (University of Bristol, UK)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK), Prof Debbie A Lawlor (University of Bristol, UK), Prof John Macleod (University of Bristol, UK), Prof Marcus Munafo (University of Bristol, UK), Dr S J Lewis (University of Bristol, UK), Dr Jon Heron (University of Bristol, UK), Prof Kate Tilling (University of Bristol, UK), Prof Anne Lingford-Hughes (Imperial College London, UK), Dr John McGonigle (Imperial College London, UK), Prof Glyn Lewis (University College London, UK), Prof Eileen Kaner (Newcastle University, UK), Prof Colin Drummond (King's College London, UK), Prof Anthony David (King's College London, UK), Prof Michael Lynskey (King's College London, UK), Prof Barbara Maughan (King's College London, UK), Prof Gunter Schumann (King's College London, UK), Prof Derek K Jones (University of Cardiff, UK), Prof Matt Field (University of Liverpool, UK), Dr Petra Meier (University of Sheffield, UK), Prof Alan Brennan (University of Sheffield, UK), Prof Kenneth Kendler (Virginia Commonwealth University, USA), Dr Danielle Dick (Virginia Commonwealth University, USA), Dr Nick Sheron (University of Southampton, UK)
Title of project: 
Excessive drinking and alcohol related harms in Adulthood: ALSPAC at 24.
Proposal summary: 

AIMS

We propose repeating the detailed MRI examinations on 125 participants from ALSPAC who were scanned at 18 years as controls for a study of psychotic symptoms (MRC, PLIKS) in order to test the hypothesis that differences in brain structure and dysregulation in function are associated with AU. Thus:-

1. We will compare MR imaging data from their first imaging session (age 18) to the second (age 24) to assess the cumulative impact of drinking alcohol during the intervening years on:

i) brain tissue macrostructure, grey and white matter, using voxel based morphometry (VBM) and cortical thickness measurements

ii) white matter microstructure, including standard diffusion tensor MRI measures (FA, mean diffusivity) and 'hindrance modulated orientational anisotropy', using diffusion MRI (dMRI), and multi-component relaxometry (mcR) to assess putative markers of myelin along specific pathways(52)

iii) activation of prefrontal cortex (PFC) during a task of working memory (n-back).

2. We will investigate whether MR imaging data (VBM, dMRI, mcR, fMRI as above) from the 1st session predicts use of alcohol during the intervening years.

Specifically we hypothesise that compared with those with limited or no drinking, those with greater cumulative alcohol consumption and those predominantly with a binge pattern during the intervening years will show: i) greater reduction in hippocampal, prefrontal, cerebellar volumes; ii) altered WM microstructure in those white matter tracts maturing later (PFC connections eg cingulum, superior longitudinal fasciculus (SLF)) compared with those maturing earlier (eg posterior limb of internal capsule; iii) greater activation during n-back task with unimpaired performance, in their 1st session and when comparing 1st and 2nd sessions.

3. We will investigate the relationship between current and cumulative alcohol consumption with MR imaging data (VBM, dMRI, mcR, fMRI as above) and from ICCAM protocol at the 2nd session, activation of PFC during inhibitory task (go-nogo(53)), activation of ventral striatum during reward task (MIDT(54)), activation of amygdala during stress (stressful images).

Date proposal received: 
Monday, 3 February, 2014
Date proposal approved: 
Thursday, 6 February, 2014
Keywords: 
Substance Use
Primary keyword: 
Alcohol