Recent research shows that traumatic stress associated with childhood abuse may interfere with the development of the brain.
Children who are abused often have cognitive, behavioral, and emotional problems and tend to develop posttrauamtic stress disorder. Recent research suggests that these problems may be related to changes in their brain.
DeBellis presented his findings at the annual meeting of the American Academy of Child and Adolescent Psychiatry last October.
Most of the subjects were diagnosed with PTSD as a consequence of sexual abuse, which began when they were between 1 and 7 years old and lasted between one and five years. Several subjects had witnessed domestic violence and/or were emotionally abused, which often coincided with the sexual abuse. A few subjects were also physically abused. All the abused children were living in stable environments without the perpetrators during the study, which was published as the second of a two-part series in the May 15, 1999, issue of Biological Psychiatry.
The results showed that abused children diagnosed with PTSD had lower intracranial and cerebral volumes, larger lateral ventricles, and a smaller corpus callosum than healthy controls, which may indicate neuronal loss, said DeBellis.
Enlargement of the lateral ventricles was associated with longer duration of abuse, increased cerebral spinal fluid in the cortex and prefrontal cortex, and PTSD symptoms of intrusive thoughts, avoidance, hyperarousal, or dissociation.
The corpus callosum connects the brain’s right and left cerebral hemispheres, and its smaller size was not associated with duration of abuse, age of onset, or PTSD symptoms. The medial prefontal cortex, which is associated with cognition and executive functioning, including decision making, planning, and working memory, was also smaller in children with PTSD, said DeBellis.
However, the researchers’ prediction that the hippocampus, which plays a role in emotional memory, would be smaller in abused children with PTSD than controls did not hold up. Smaller hippocampal volumes have been reported in veterans with combat-related PTSD, but DeBellis commented that the veterans also had high rates of comorbid alcohol abuse, which he believes is a stronger factor than PTSD in the hippocampus.
The decrease in intracranial volume was associated with early-onset abuse in children with PTSD. "We found that the intracranial volume grew until age 5 and then fell off, which is worrisome," said DeBellis. "We must consider that the smaller volumes may be associated with permanent neuronal loss leading to lower IQ scores."
In healthy children, intracranial volume increases steadily until age 10, with 75 percent of the adult brain weight occurring by age 2, and 95 percent by age 5, he said.
Brain development begins in utero with an overproduction of neurons, which are selectively eliminated by age 4 by a process called pruning, according to DeBellis. Synapses grow (synaptogenesis) and connect neurons together, and their numbers are pruned in late childhood and through the third decade of life.
Neurons enlarge with age and axons thicken. Between the ages of 5 and 18 years, the process of coating the neurons in the central nervous system with a myelin sheath is most influential in determining brain size, said DeBellis.
"In the PTSD children, we saw that the corpus callosum did not grow with age compared with controls, which may be due to a failure of myelination," said DeBellis.
His earlier study of abused children with PTSD (part 1 in the May 15, 1999, issue of Biological Psychiatry) suggests that traumatic stress in children produces chemical changes in the brain that disrupt or alter these developmental processes.
Eighteen abused children with PTSD were compared with 10 children with generalized anxiety disorder (GAD) and 24 controls. Fifteen of the PTSD group had been sexually abused, and 11 of those children had also witnessed domestic violence. The average age of onset for sexual abuse was 4 years, with an average duration of two years. The average onset for witnessing domestic violence was 2 years, with an average duration of five years before disclosure, according to DeBellis.
The PTSD group had higher levels of the catecholamine neurotransmitters norepinephrine, dopamine, and epinephrine than the group with GAD and higher levels of cortisol than healthy controls.
The longer duration of abuse corresponded with increased levels of the catecholamine neurotransmitters and cortisol in the PTSD group and severity of PTSD symptoms, according to DeBellis.
Symptoms of hyperarousal, intrusive thoughts, and avoidance were associated with increased levels of norepinephrine, dopamine, and cortisol, according to the study.
The neurobiological pathway for PTSD is essentially the "fight or flight" response to fear. The amygdala, which is the seat of emotional memory in the brain, sets off a chain reaction in the rest of the limbic system and the hypothalamus, pituitary, and adrenal glands (HPA axis). The HPA axis produces corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH), and cortisol. These events stimulate the sympathetic nervous system and the brain to produce catecholamines, according to DeBellis.
A handful of studies has shown elevated catecholamine levels in abused children who had mood and anxiety disorders and did not meet the full criteria for PTSD. Other studies of maltreated children have shown that dysregulation of the HPA axis plays a role in the increased levels of cortisol throughout the day, said DeBellis.
"Results of animal studies suggested that higher levels of catecholamines and cortisol may adversely affect brain development through accelerated loss of neurons, delays in myelination, or abnormalities in developmentally appropriate pruning of neurons," said DeBellis.
He investigated the neuronal loss theory in a pilot study published in the July 2000 American Journal of Psychiatry. The researchers hypothesized that the level of N-acetylaspartate (a marker of neuronal integrity) relative to creatine (a stable measure of overall brain metabolism) would be lower due to increased metabolism and decreased neurons in the anterior cingulate.
Magnetic resonance spectroscopy was used to see the levels of N-acetylaspartate to creatine in 11 abused children with PTSD and 11 healthy controls.
The cingulate gyrus is located above the corpus callosum in the brain, and a lack of blood flow to the cingulate area has been implicated in PTSD in combat veterans and sexually abused women, according to DeBellis.
"We saw lower levels of N-acetylaspartate to creatine in the abused subjects compared with controls, which may reflect global neuronal loss in childhood PTSD. Our previous MRI findings of global brain differences in abused children with PTSD appear to support this theory," said DeBellis.
In another study, he measured the N-acetylaspartate to creatine ratio of an abused boy with PTSD he had treated with clonidine. Clonidine is an antihypertensive drug that blocks high levels of catecholamines, specifically norepinephrine. The results, published in the fall 2001 Journal of Child and Adolescent Psychopharmacology, showed that the boy’s PTSD symptoms were in remission and that the level of N-acetylaspartate to creatine increased at six months and was sustained at 18 months, indicating neuronal growth, said DeBellis.
He recognized the limitations of these studies including small sample sizes and cross-sectional designs. He is attempting to replicate some of the findings in a larger longitudinal study. ▪