The neural correlates of emotional memory in posttraumatic stress disorder and the mediating role of genetic influences.

摘要

Background. PTSD is marked by intrusive, chronic, and distressing memories of highly emotional events. Previous research has highlighted the role of the amygdala and its interactions with the hippocampus in mediating the effect of enhanced memory for emotional information in healthy individuals. As the functional integrity of these regions may be compromised in PTSD, the current study sought to examine the neural correlates of emotional memory in PTSD. Additionally, research has documented a mediating role of the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism on amygdala activity and anxious behaviors as well as mediating roles of the catechol-Omethyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) polymorphisms on hippocampal activity and memory performance. As such, the current study sought to examine the potentially mediating roles of these three common genetic polymorphisms on the neural correlates of emotional memory in PTSD.;Methods. We used functional magnetic resonance imaging (fMRI) and an event-related subsequent memory paradigm to study amygdala and hippocampus activation in 18 individuals with PTSD and 18 trauma-exposed non-PTSD (TENP) control participants genotyped for the candidate genes 5-HTTLPR, BDNF, and COMT. The stimuli were negative and neutral pictures from the International Affective Picture System. Recognition memory was assessed one week following encoding.;Results. Memory enhancement for negative, relative to neutral, pictures was found across all subjects. This effect did not significantly differ between groups. Relative to the TENP group, the PTSD group showed exaggerated amygdala activation during the encoding of negative vs. neutral pictures; this effect was even more pronounced when the analysis included data from only those pictures that were subsequently remembered one week later. In the PTSD group, degree of amygdala activation during the encoding of negative vs. neutral pictures was positively correlated with both hippocampal activation and current PTSD symptom severity. Additionally, hippocampal activation associated with the successful encoding of negative relative to neutral pictures was significantly greater in the PTSD group relative to the TENP group. We failed to find a strong association between 5-HTTLPR, BDNF, or COMT status and memory for negative relative to neutral pictures nor with the amygdala or hippocampal activity associated with the encoding of negative relative to neutral pictures. However, analysis of interactions between polymorphism status and PTSD status was limited given the disproportionate genetic breakdown among the groups.;Conclusions. Exaggerated amygdala activation during the encoding of emotionally negative stimuli in PTSD is related to symptom severity and to hippocampal activation, suggesting a role for these structures in the pathophysiology of this disorder. Further research will be needed to determine whether these functional brain abnormalities act as risk factors for or acquired characteristics of PTSD. Additionally, replication in a much larger sample would be required in order to draw any significant conclusions with respect to the roles of 5-HTTLPR, BDNF, and COMT (and potential interactions between these polymorphisms) as they relate to emotional memory in PTSD.