Impact of FAAH Genotype and Marijuana Use on Brain Structure and Neuropsychological Performance in Emerging Adults
Date of Award
Master of Science
Krista M. Lisdahl
Christine Larson, Cecilia Hillard
Adolescence, Brain, DTI, Genetics, Gyrification, Marijuana
Introduction: Chronic MJ use may be associated with higher cognitive ability impairments (see Lisdahl et al., 2013). Regions undergoing later maturation (Gogtay 2004), may be at increased risk for MJ-induced alterations. Endogenous cannabinoid signaling (ECS) is modulated by the function the enzyme Fatty Acid Amide Hydrolase (see Ho & Hilard, 2005), thus the gene encoding for this enzyme (FAAH) impacts ECS (Sipe et al., 2002). Here, we examine the impact of MJ use and FAAH genotype on PFC complexity and underlying frontal white matter (WM) integrity in young adults. Methods: Participants included 37 MJ users and 37 non-using young adults (ages 18-25). Of those, 27 were FAAH A carriers and 47 were homozygous (C/C) carriers. Exclusion criteria included co-morbid psychiatric and neurologic disorders and excessive other drug use. Brain complexity and WM integrity was measured using local gyrification index and Tracula programs. The Letter Number Sequencing, PASAT and D-Kefs c/w interference measured complex attention and inhibition. Multiple regressions and Pearson r correlations were used to predict LGI, WM integrity and cognitive performance indices from MJ use status, FAAH status, and MJ*FAAH interactions controlling for demographic variables and comorbid drug use. Results: MJ users demonstrated decreased LGI in bilateral vmPFC (RH: [beta=-.54, p<.001] and LH: [beta=-.55, p<.001]); bilateral mPFC (RH: [beta=-.48, p=.001] and LH: [beta=-.51, p<.001]); and bilateral frontal poles (RH: [beta=-.31, p=.02]; LH: [beta=-.43, p=.004]), with increased LGI in LH DLPFC [beta=.40, p=.004]. Controlling for the same variables, reduced WM integrity was found in bilateral UCF (RH: [beta=.32, p=.03] and LH: [beta=.31, p=.03]) and fMinor [beta=.27, p=.05] tracts of MJ users. Significant interactions between MJ*FAAH were seen predicting LGI in LH OFC [beta=-.24, p=.04] and WM integrity in fMinor [beta=.26, p=.04] and LH ATR [beta=.36, p=.003]. In MJ users, increased gyrification was associated with better LNS performance in RH mPFC [r=.51, p=.001], RH vmPFC [r=.41, p=.01], and RH frontal pole [r=.45, p=.005] and a negative correlation with gyrification and color-word completion time in LH vmPFC [r=-.32, p=.05]. In MJ users, decreased WM integrity was associated with greater PASAT performance in the RH UNC [r=.38, p=.02]. Discussion: MJ use was associated with reduced LGI in several PFC regions with one region showing an opposite relationship. These results are consistent with Mata and colleagues (2010). We also found reduced WM integrity in fronto-temporal tracts, which may have important emotion regulation implications. These brain characteristics were also moderated by FAAH genotype. Additional implications of ECS and brain health will be discussed.
Shollenbarger, Skyler Gabriel, "Impact of FAAH Genotype and Marijuana Use on Brain Structure and Neuropsychological Performance in Emerging Adults" (2014). Theses and Dissertations. 761.