Abused Children May Develop Subtle Physiological Changes

Progress may be slow, but research continues to lay down the building blocks that connect the external world to the brain cells of the growing child. Study of the influence of early adversity on childhood development, for example, began with epidemiology and continues with more specific techniques such as genetics and imaging.

“This may be a relatively underfunded and understudied area, but we are as close to understanding the mechanisms of gene/environment interactions with child development as anything else in psychiatry,” said Frank Putnam, M.D., a professor of pediatrics and psychiatry and director of the Mayerson Center for Safe and Healthy Children at Children's Hospital Medical Center in Cincinnati.

For instance, a recent study using magnetic resonance imaging has linked childhood sexual abuse with reduced gray-matter volume in the brain.

The researchers compared MRIs of 23 unmedicated young women aged 19 or 20 who reported at least three episodes of being the victim of forced child sexual abuse before age 18 with MRI images from 14 matched control subjects. The scans revealed reduced gray-matter volume in two areas of the brains of the women who had been abused.

On average, there was an 18.1 percent reduction in volume in the left visual cortex and a 12.6 percent reduction in the right visual cortex of the child sexual abuse subjects, wrote Akemi Tomoda, M.D., Ph.D., of the Developmental Biospychiatry Research Program at McLean Hospital in Belmont, Mass., and colleagues in the October 1 Biological Psychiatry.

Further analysis found that gray-matter volume correlated with the duration of child sexual abuse that took place before age 12, but there was no similar correlation with duration of abuse after age 12 or with age of onset of abuse.

This suggested, the authors said, “that exposure to abuse affects visual cortex development, but that vulnerability is limited to an early, sensitive period.”

The neurobiological changes during development may be adaptive for victims of child sexual abuse, said Tomoda and colleagues. “[T]he child's brain may endeavor to reduce stress by attenuating the development of sensory systems and pathways relaying recurrent aversive or traumatic experiences.”

“These changes in the visual cortex are somewhat unexpected findings,” said Putnam, who was not involved in the study. “Earlier studies have provided evidence on processing activity in the visual cortex, but this study may be the first to show differences in its structure.”

Tomoda and colleagues also analyzed a subset (n=14) of abused subjects who had not been diagnosed with Axis I psychiatric disorders and found a significant reduction in gray-matter volume among these participants as well. Such changes in the visual cortex may also “help explain the tendency of some patients to interpret ambiguous facial expressions as angry,” they said.

A different study found that two variants in the corticotropin-releasing hormone receptor (CRHR1) gene linked the effects of childhood maltreatment to cortisol responses on a standard test. In this case, maltreatment was defined as a moderate to severe score on the Childhood Trauma Questionnaire scales for physical abuse, sexual abuse, emotional abuse, physical neglect, or emotional neglect.

The researchers in this study recruited 129 white, non-Hispanic volunteers. They included 91 with little or no maltreatment and 38 with moderate to severe maltreatment. Maltreated subjects were more likely to be older, to have higher body mass indices, and to have had depression or alcohol problems than those who were not maltreated. The subjects were evaluated with the Structured Clinical Interview for DSM-IV and the Childhood Trauma Questionnaire. The dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test was used to measure cortisol, and the subjects' DNA was genotyped for two single-nucleotide polymorphisms in the CRHR1 gene.

The presence of one of the three alleles (called GG) of both single-nucleotide polymorphisms was associated with higher cortisol responses to the test, wrote Audrey Tyrka, M.D., Ph.D., of the Butler Hospital in Providence, R.I., and colleagues, in the same issue of Biological Psychiatry.

“Given the role of the Type I receptor in the activation of the HPA axis, as well as involvement in extrahypothalamic brain regions and the behavioral response to stress, these findings suggest that this genotype might increase neurosensitivity to stress,” wrote Tyrka and colleagues. The other alleles, which did not show the same effect, might offer some resilience against stress or adversity, they said.

“The GG variant does show a real difference in the maltreated group,” said Putnam. “We've seen data on the dysregulation of the HPA axis and psychiatric outcomes for a decade, but this study gets more at the mechanism involved. It shows how child sexual abuse interacts in a complex way with genomics and the environment and leads to high rates of comorbidity and outcomes associated with trauma.”

However, Putnam suspected that as in all studies comparing abused and supposedly nonabused subjects, the latter cohort may harbor persons who are unwilling to reveal a history of abuse. Such potential covert abuse among the controls may muddy the data, he said.

Similar studies in cohorts with greater ethnic and racial diversity, as well as including subjects with psychosis or bipolar disorder, would match clinical populations more closely, he noted.

Overall, child maltreatment is an often unrecognized variable, invisible in many studies, said Putnam. He added that researchers investigating childhood issues other than child abuse could easily add the Childhood Trauma Questionnaire to their studies to permit controlling for such adversity.

An abstract of “Childhood Sexual Abuse Is Associated With Reduced Gray-Matter Volume in Visual Cortex of Young Women” is posted at <www.journals.elsevierhealth.com/periodicals/bps/article/S0006-3223(09)00507-1/abstract>. An abstract of “Interaction of Childhood Maltreatment With the Corticotropin-Releasing Hormone Receptor Gene: Effects on Hypothalamic-Pituitary-Adrenal Axis Reactivity” is posted at <www.journals.elsevierhealth.com/periodicals/bps/article/S0006-3223(09)00634-9/abstract>.