The exposure to trauma, such as parental mental illness and household dysfunction, during early childhood period is a recognized risk factor for later development of anxiety and mood disorders. Only a fraction of children who experience traumatic stress, however, actually develop anxiety or mood disorders in adulthood, even though many youth are exposed to severe adversity during childhood. Thus, the enduring question in the study of stress-related neuropsychiatric illness is why some individuals are more susceptible to the traumatic effects of stress than others.

Findings of a new study, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, indicate that childhood trauma alters the brain circuits involved in affective processing, and, consequently, influences stress adaptation (vulnerability or resilience) and the development of anxiety or mood disorders in adolescence. Also, findings show that “childhood, but not late adolescence, is a particularly important developmental period in determining neural adaption to adversity,” the authors write in their publication.

Scientists followed 132 participants from infancy to 18 years, and, during the process, collected the information about participants’ exposure to childhood adversity (ie, family adversity levels during infancy to age 11, including maternal depression, negative parenting, parental conflict/family anger, maternal role overload, and financial stress). They assessed adolescent internalizing symptoms four times per year, from ages 15 to 18, by using the adolescent version of the MacArthur Health and Behavior Questionnaire. An absence of symptoms of anxiety and depression was used to operationalize emotional adaptation.

When subjects were 18 years old, researchers performed functional MRI analysis during an emotion-processing task in which participants were instructed to rate picture valance via button press and were not explicitly instructed to regulate their emotional responses. Participants were shown images that evoke positive, negative, or neutral emotions.

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Investigators examined the effects of childhood adversity, adolescent internalizing, and their interaction on neuroanatomic substrates of adversity adaptation. More specifically, they examined activation patterns and functional connectivity in prefrontal-amygdala and prefrontal-hippocampal pathways.

Nearly 30% of participants had a lifetime diagnosis of any internalizing disorder, whereas 14% and 12% of participants had a lifetime diagnosis of major depressive disorder (MDD) or social anxiety disorder, respectively. More than 5% of participants had a lifetime diagnosis of attention-deficit/hyperactivity disorder (ADHD).

Consistent with previous reports, results of this study indicate that childhood adversity predicts greater amygdala reactivity to negative vs. neutral images in adolescence (reactivity is defined as activation 2-6 seconds after image onset). Analysis of a priori regions for the negative-neutral image contrast revealed that right amygdala (but not prefrontal cortex or hippocampus) reactivity was positively correlated with childhood adversity (k = 141 voxels, peak t = -3.07, x y z = 20, -4, -24).

In terms of amygdala functional connectivity, researchers analyzed the negative vs. neutral contrast, and data show that childhood adversity positively predicted functional connectivity of the right amygdala to bilateral medial prefrontal cortex [in adolescence]. This relationship was, however, moderated by internalizing symptoms.

With regard to hippocampal functional connectivity, researchers analyzed the negative vs. neutral contrast, and data show that childhood adversity positively predicted functional connectivity of the left and right hippocampus to bilateral dorsomedial/dorsolateral prefrontal cortex. No interaction was observed between childhood adversity and adolescent internalizing.

“These results implicate childhood as a critical developmental period in the brain’s response to adversity, potentially tipping emotion regulatory circuits toward adaptation or vulnerability by late adolescence,” the authors noted. Data point to a potential neurobiological mechanism that drives the observed adaptation to adversity in a subgroup of individuals. More specifically, “childhood adversity is associated with augmentation of prefrontal-amygdala coupling in adolescents with lower internalizing,” the authors write.

The findings of this study increase our knowledge of neuroanatomic substrates that may influence the development of anxiety and mood disorders in adolescence following childhood adversity, and will possibly facilitate the development of novel behavioral or pharmaceutical approaches to treatment of stress-related neuropsychiatric illness.

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Herringa RJ, Burghy CA, Stodola DE, et al. Enhanced prefrontal-amygdala connectivity following childhood adversity as a protective mechanism against internalizing in adolescence. Biol Psychiat: Cognitive Neuroscience and Neuroimaging. 2016;1:326-334.