Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals

Abstract

Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.

Genetics of resilience: Implications from genome‐wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression

“…Several studies have shown an association between the S allele variant of this gene and PTSD and MDD in relation to experienced stress and adversity (Karg et al, ; Xie et al, ) as well as a lower level of resilience in S allele carriers (Stein et al, ). Another promising candidate of the catecholaminergic system is COMT , whose variants also show a gene × environment interaction effect, with Met allele carriers who experienced trauma or adversity in childhood exhibiting a greater risk for the development of PTSD and depression and thus appearing to be less resilient (Valente et al, ; van Rooij et al, ). The HPA axis also appears to have an influence on resilience, particularly for the CRHR1 and FKBP5 genes, with interesting results suggesting a link between genetic variants and maltreatment during childhood and the development of PTSD and depression (Bradley et al, ; Polanczyk et al, ; Tamman et al, ).…”

“…Homozygous carriers of the Met allele show lower emotional resilience against negative mood states in humans (Smolka et al, ) and exaggerated stress reactivity in mice (Papaleo et al, ). The Met allele was found to be associated with decreased inhibition‐related activation in the hippocampus, which in turn was associated with PTSD and depression symptoms in patients with childhood trauma (van Rooij et al, ). An accumulation of the Met allele was also found in individuals who developed PTSD after being exposed to urban violence (Valente et al, ).…”

Medical Yoga Therapy

“…Meditation has been shown to increase the thickness of the left hippocampus, the region of the brain that functions in the formation of long-term memory, emotional regulation and cognition, as well as being a critical area of the brain that plays a vital role in the resiliency to chronic stress and depressive states, possibly due to expression of hippocampal neurotrophic protein (brain-derived neurotropic factor or BDNF) [ 59 ]. Resiliency to stress, stress-related depression and post-traumatic stress are housed in the hippocampus—multiple studies have shown that increased hippocampal activation correlated negatively with post-traumatic stress disorder (PTSD) and depression symptoms, and positively with resilience [ 25 , 55 , 60 , 61 , 62 ]. PTSD patients show considerable reduction in volume of the hippocampus, decreased ventromedial PFC activity and insufficient inhibition of the amygdala, all resulting in increased fear, persistent negative emotions, impulsivity, anxiety and depressive rumination.…”

Distinct neural correlates of trait resilience within core neurocognitive networks in at-risk children and adolescents

“…These neuroimaging studies have documented reduced threat-related amygdala and insula reactivity, altered reward-related responding in corticostriatal reward circuitry, and widespread changes in regional brain volumes in individuals who did not develop psychopathology. To our knowledge, only five neuroimaging studies have assessed the neural correlates of trait resilience ( Daniels et al, 2011 ; New et al, 2009 ; Reynaud et al, 2013 ; van Rooij et al, 2016 ; Waugh et al, 2008 ). Of note, these studies are all in adults.…”