title: Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults.
abstract: BACKGROUND
  The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms.
  
  
  METHODS
  Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18-25). Multiple regressions examined the independent and interactive effects of variables on WM integrity.
  
  
  RESULTS
  Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC.
  
  
  CONCLUSIONS
  Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Garland Hall Rm 224, 2441 East Hartford Ave, Milwaukee, WI 53211, USA.
authors.forename: Skyler G
authors.initials: SG
authors.lastname: Shollenbarger
authors.affiliation: McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
authors.forename: Jenessa
authors.initials: J
authors.lastname: Price
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Garland Hall Rm 224, 2441 East Hartford Ave, Milwaukee, WI 53211, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Wieser
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Garland Hall Rm 224, 2441 East Hartford Ave, Milwaukee, WI 53211, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Lisdahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000581:Amidohydrolases / Q000235:genetics*; D057565:Apathy / Q000502:physiology*; D002188:Cannabis / Q000009:adverse effects*; D003863:Depression / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000473:pathology; D005838:Genotype; D006801:Humans; D008032:Limbic System / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D066127:White Matter / Q000187:drug effects* / Q000473:pathology; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000099252:Fatty Acid Amide Hydrolases
keywords: Cannabis; Depression; Diffusion tensor imaging; Emerging adults; FAAH; Frontolimbic