By Will Boggs MD

NEW YORK (Reuters Health) - Adolescents with a history of childhood trauma show different neural responses to subjective anxiety and craving, researchers report.

"I think the finding of increased activation of insula, anterior cingulate, and prefrontal cortex in response to stress cues in the high- relative to low-trauma group, while arguably not necessarily unexpected, is important as it suggests that youth exposed to higher levels of trauma may experience different brain responses to similar stressors," Dr. Marc N. Potenza from Yale University, New Haven, Connecticut told Reuters Health by email.

Childhood trauma has been associated with anxiety and depression, as well as obesity, risky sexual behavior, and substance use. Previous imaging studies have not investigated neural responses to personalized stimuli, Dr. Potenza and his colleagues write in Neuropsychopharmacology, online January 8.

The team used functional MRI to assess regional brain activations to personalized appetitive (favorite food), aversive (stress), and neutral/relaxing cues in 64 adolescents, including 33 in the low-trauma group and 31 in the high-trauma group.

Two-thirds of the adolescents had been exposed to cocaine prenatally, with prenatal cocaine exposure being significantly over-represented in the high-trauma group.

Compared with the low-trauma group, the high-trauma group showed increased responsivity in several cortical regions in response to stress, as well as decreased activation in the cerebellar vermis and right cerebellum in response to neutral/relaxing cues. But the two groups did not differ significantly in their responses to favorite-food cues, the researchers found.

The high-trauma group had activation in the left hippocampus/parahippocampus, posterior caudate, posterior insula, thalamus, temporal pole, and midbrain that was inversely correlated with post-imagery anxiety.

Both groups showed inverse correlations between food craving and corticostriatal activation in the favorite-food condition, with no significant differences between the groups, according to the report.

"The present findings suggest that childhood trauma leads to neural hyper-responsivity to acute stress in prefrontal regulatory regions as well as the insula," the researchers explain. "Hypoactivation of subcortical structures, notably the hippocampus, was associated with anxiety in the response to stress cues, specifically in the high-trauma-exposed group. Trauma exposure was also linked to hypoactivation of cerebellar regions in response to the neutral/relaxing cues. These differences were observed in the absence of contemporaneous psychiatric disturbances."

"These findings suggest the possibility that there might exist different sensitivities to the relative allocation of brain resources to stressful stimuli in the environment and may hold multiple implications for prevention and treatment efforts," Dr. Potenza said. "An important observation is that the neural correlates of trauma appear to differ from those of prenatal cocaine exposure in the same sample."

"Studies like this help us to understand how exposure to trauma in early life impacts child development," Dr. Moriah E. Thomason from Wayne State University School of Medicine in Detroit, Michigan, told Reuters Health by email. "We can gaze into the active brain and discover how it functions differently following maltreatment. This provides us with mechanistic insight that is not obvious in behavior alone."

"For example," she said, "these researchers observed that the hippocampus is under-active in maltreatment-exposed adolescents. We can take a step back and consider the role that the hippocampus plays in processing cognitive and emotional material. With that there is potential to develop behavioral interventions suited to strengthen function in the hippocampus, a region critical for learning and memory, and one that grows new brain cells throughout the life span."

"Many studies have looked at brain differences in adults that experienced maltreatment in childhood, but far fewer have evaluated these in early life -- at the time when the effects are likely to interfere with development," Dr. Thomason said.

"Future studies will evaluate interventions informed from these basic science discoveries," Dr. Thomason concluded. "Additionally, there is a potential for brain function to become a prognostic indicator of which children are most likely to go on to experience negative mental and physical health outcomes. Improved prognostic information would be of value in advising families and developing customized treatment plans."


Neuropsychopharmacology 2015.