title: White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study.
abstract: BACKGROUND
  Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse.
  
  
  METHODS
  Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI.
  
  
  RESULTS
  This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution.
  
  
  CONCLUSIONS
  Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery.
  
  
  BACKGROUND
  US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Rosenbloom
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chu
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Sassoon
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Rohlfing
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kilian M
authors.initials: KM
authors.lastname: Pohl
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Zahr
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: edie@stanford.edu.
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan