Genetic variation in endocannabinoid signaling: Anxiety, depression, and threat- and reward-related brain functioning during the transition into adolescence.

BACKGROUND: The endocannabinoid system modulates neural activity throughout the lifespan. In adults, neuroimaging studies link a common genetic variant in fatty acid amide hydrolase (FAAH C385A)-an enzyme that regulates endocannabinoid signaling-to reduced risk of anxiety and depression, and altered threat- and reward-related neural activity. However, limited research has investigated these associations during the transition into adolescence, a period of substantial neurodevelopment and increased psychopathology risk. METHODS: This study included FAAH genotype and longitudinal neuroimaging and neurobehavioral data from 4811 youth (46% female; 9-11 years at Baseline, 11-13 years at Year 2) from the Adolescent Brain Cognitive DevelopmentSM Study. Linear mixed models examined the effects of FAAH and the FAAH x time interaction on anxiety and depressive symptoms, amygdala reactivity to threatening faces, and nucleus accumbens (NAcc) response to happy faces during the emotional n-back task. RESULTS: A significant main effect of FAAH on depressive symptoms was observed, such that depressive symptoms were lower across both timepoints in those with the AA genotype compared to both AC and CC genotypes (p's<0.05). There were no significant FAAH x time interactions for anxiety, depression, or neural responses (p's>0.05). Additionally, there were no main effects of FAAH on anxiety or neural responses (p's>0.05). CONCLUSIONS: Our findings add to emerging evidence linking the FAAH C385A variant to lower risk of psychopathology, and extend these findings to a developmental sample. In particular, we found lower depressive symptoms in FAAH AA genotypes compared to AC and CC genotypes. Future research is needed to characterize the role of the FAAH variant and the eCB system more broadly in neurodevelopment and psychiatric risk.

Attention, attention! Posttraumatic stress disorder is associated with altered attention-related brain function.

Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered arousal, mood, and cognition. Studies report attentional alterations such as threat bias in individuals with PTSD, though this work has largely been conducted within emotionally-charged contexts (e.g., threatening stimuli). Emerging behavioral evidence suggests that PTSD-related attention deficits exist even in the absence of threatening cues or anxiety triggers. However, the role and functioning of attention brain circuits as they relate to PTSD remains underexplored. In this mini review, we highlight recent work using non-emotional stimuli to investigate the neurobiology of attention and disruptions to attention-related brain function among individuals with PTSD. We then discuss gaps in the current literature, including questions pertaining to the neural circuitry of attentional alterations in PTSD, as well as the contributions that trauma exposure, PTSD symptoms, comorbidities, and pre-existing vulnerabilities may have in this relationship. Finally, we suggest future directions for this emerging area of research, which may further inform knowledge surrounding the neurobiological underpinnings of PTSD and potential treatments.