Our Earlier Studies

We first began exploring the neurobiological underpinnings of CA by examining individuals with borderline personality disorder who had (a) symptoms indicative of temporal lobe epilepsy (TLE), (b) abnormal electroencephalograms (EEG) consisting of spike and sharp waves, and (c) findings of temporal mesial sclerosis or dilated temporal horns as observed with magnetic resonance imaging or computed tomography (Teicher, Glod, Surrey, & Swett, 1993). Given that these individuals all had a history of CA—together with animal models of kindling—we hypothesized that CA exerts a deleterious effect on limbic system elec-trophysiology or development. Using the Limbic System Checklist (LSCL-33) to assess symptoms typically encountered by persons with TLE during seizures with 253 consecutive admissions to an adult outpatient clinic, we found that scores were significantly elevated in subjects with a self-reported history of childhood sexual or physical abuse. For those subjects who experienced both physical and sexual abuse, LSCL-33 scores were comparable to subjects with documented TLE. In a subsequent study with 115 consecutive admissions to a child and adolescent center, the incidence of clinically significant EEG abnormalities (i.e., spike waves, sharp waves, and paroxysmal slowing) was observed to be markedly greater in children with abuse histories than those who were never exposed to abuse (Ito et al., 1993). Furthermore, children with a documented history of severe physical and/or sexual abuse had a 72% incidence of abnormal EEG readings. Contrary to the premise that the EEG abnormalities were preexisting, preclinical studies provide evidence that exposure to early stress can indeed induce such anomalies. For example, Heath and colleagues (Heath, 1973; Heath & Harper, 1974) studied monkeys raised in isolation by Harry Harlow and documented spike waves in the hippocampus and fastigial nuclei, which project from the cerebellar vermis to a variety of brain structures such as the hippocampus.

As a follow-up, we used EEG coherence to assess cortical maturation and differentiation (Ito, Teicher, Glod, & Ackerman, 1998) and found that the left cortex of 15 healthy right-handed children was more developed than their right cortex, which is consistent with what is known about the anatomy of the dominant hemisphere (Galaburda, 1991). In contrast, EEG coherence revealed that the right hemispheres were significantly more developed than the left hemispheres in 15 child psychiatric inpatients with a documented history of CA, even though all subjects were right-handed. Although coherence measures indicated that the right hemisphere of CA subjects was comparable to that of control subjects, their left hemisphere lagged substantially behind the left hemisphere of the healthy children. This lateralized effect of CA was further supported in a study by Schiffer, Teicher, and Papanicolaou (1995).

As previously noted, the corpus callosum is one brain area that has received recent attention in the CA literature. Advancing the pioneering preclinical contributions of Denenberg (Denenberg, 1983; Denenberg, Garbanati, Sherman, Yutzey, & Kaplan, 1978; Denenberg & Yutzey, 1985), Sanchez, Hearn, Do, Rilling, and Herndon (1998) observed diminished corpus callosal size, in particular the midsaggital area, of male rhesus monkeys that were raised in relative isolation compared to monkeys living in a seminatural environment. In parallel, we examined the corpus callosum in children hospitalized for psychiatric disorders and also found a substantial reduction in the midsaggital area of those children who additionally had a history of abuse or neglect, especially in males (Teicher et al., 1997). This finding was replicated in a more comprehensive study of children with abuse-related PTSD (De Bellis et al., 1999). Although the clinical consequences of reduced corpus callosum area are not fully understood, some preliminary work from our research program illustrates how this brain alteration might influence emotional memory (see below).

To more fully understand our limbic findings, we used T2 relaxometry— a noninvasive means of ascertaining resting regional cerebral blood volume (Teicher et al., 2000)—to examine the relationship between cerebellar vermis functionality and limbic irritability symptoms in young adults (Anderson, Teicher, Polcari, & Renshaw, 2002). A strong correlation was observed between T2 relaxation time and the degree of limbic irritability on the LSCL-33 in all subjects. However, at any level of limbic symptomatology, a marked decrease in the relative perfusion of the vermis appeared specific to those individuals who had CA histories. Consequently, we interpreted this finding as indicative of a functional impairment of cerebellar vermis activity. This conclusion is consistent with preclinical studies demonstrating that isolation-reared monkeys with behavioral disturbances have epileptiform spike and sharp-wave activity in their fasti-gial nucleus (output nucleus of the cerebellar vermis) and hippocampus (Heath, 1973; Heath & Harper 1974).

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