Archive for December, 2008

Abuse and Sensitive Periods

December 14, 2008

Research from my laboratory, and from other labs here and abroad, have shown that exposure to childhood abuse is associated with alterations in brain structure and function.  This research has largely focused on brain regions known to be susceptible to the effects of stress, such as the hippocampus.  We have recently expanded our knowledge regarding the potential adverse effects of abuse by publishing the first preliminary data indicating that the neurobiological consequences of abuse depend on the age of exposure (Andersen et al 2008).

Andersen SL, Tomada A, Vincow ES, Valente E, Polcari A, Teicher MH (2008): Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. J Neuropsychiatry Clin Neurosci 20:292-301.

Synopsis:

Childhood Abuse and Regional Brain Development: Evidence for Sensitive Periods

Martin H. Teicher, Susan L. Andersen, Akemi Tomada, Evelyn Vincow, Elizabeth Valente, & Ann Polcari

Department of Psychiatry, Harvard Medical School; Developmental Biopsychiatry Research Program, McLean Hospital, Belmont MA 02478

Background

The brain is molded by experiences that occur throughout the lifespan. However, there are particular stages of development when experience exerts either a maximal (sensitive period) or essential (critical period) effect. Little direct evidence exists for sensitive or critical periods in human brain development. Based on differential rates of maturation specific brain regions should have their own unique periods of sensitivity to the effects of early experiences such as stress.

To ascertain if this is true in humans, the size of apriori selected target regions were measured from high-resolution volumetric MRI scans (1.5 T GE Echospeed) from unmedicated collegiate females with a history of repeated childhood sexual abuse and healthy sociodemographically comparable controls.

Subjects

Physically healthy, unmedicated, right-handed individuals aged 18–22 years with history of 3 or more episodes of forced contact childhood sexual abuse (CSA) prior to age 18.  Subjects had no history of neurological disorders; psychotic disorders; pregnancy; past or present alcohol/substance abuse; in utero exposure to alcohol or drugs; complication during prenancy or delivery; physical abuse  above shoulders; or exposure to any other forms of trauma. Abused and control subjects were predominantly middle class or above (96%) and the two groups were similar in measures of socioeconomic status (Hollingshead index (23): 2.3±0.9 versus 2.0±0.6; p = 0.17).  Subjects were paid for their participation, provided written, informed consent, and the study was approved and monitored by the McLean Hospital Institutional Review Board.

•CSA group:  26 abused women (mean age = 20.0 yr).
•Controls: 17 women (mean age = 19.4 yr) with no current or past DSM-IV Axis I disorder and no history of abuse or exposure to other traumatic events.

MRI Methods

Volumetric brain images were acquired using a 1.5 T magnetic resonance scanner (Echospeed; General Electric Medical Systems, Milwaukee, WI, USA) .   Hippocampus and amygdala were manually traced in their entirety according to the method detailed by Pruessner et al. (2000).   Anatomical measurements of corpus callosum area were obtained from the midsagittal image.  An automated algorithm created in NIH Image divided the manually-traced corpus callosum into seven regions as defined by Witelson (1989).  Region 3, rostral body, was selected for sensitive period analysis as this region showed the greatest overall vulnerability to CSA in the present sample.  Frontal cortex grey matter volume and intracranial  volume were ascertained using a semi-automated  program for cortical surface-based analysis (FreeSurfer; Dale et al., 1999; Fischl et al 1999, 2001).

Data Analysis

First, an exploratory analysis was performed using ANCOVA to compare brain regions in subjects who experienced CSA during a development stage (preschool 3-5 yrs, latency 6-8 yr,  prepubertal 9-10 yr, pubertal 11-13 yr and adolescent14-16 yr) versus healthy controls (“abuse-control comparison”). If a brain region was vulnerable at a particular stage, it should differ in size in subjects who experienced abuse at that stage relative to controls. Further, if one developmental stage was markedly more vulnerable than another developmental stage, then subjects who experienced CSA during the vulnerable stage should also show differences in regional brain size compared to subjects who experienced CSA during other stages (“within abuse comparison”).

To compensate statistically for the number of multiple comparisons made in each analysis, a sequential Sidak Bonferroni-type multiple comparison  procedure was used to adjust reported p-values {Sidak1967, Holland 1988}.

Second, path analysis was performed using structural equation modeling with Amos Graphics as a confirmatory statistical procedure.  Path analysis was used to simultaneously examine the association between the density of abuse during each of the aforementioned stages and measures of the hippocampal volume, frontal cortex GMV, and midsaggital area of the rostral body of the corpus callosum.
Results

hipp_sens_period028

Figure 1.  Effect of exposure to childhood sexual abuse during different developmental stages on measures of hippocampal volume during early adulthood.  Data based on ANCOVA, with results expressed as effect size (eta-squared), indicating percent of variance that can be attributed to abuse during a given stage.

sens_period_color0012
Figure 2.  Path analysis based on structural equation modeling with Amos Graphics, showing the relationship between density of abuse during different developmental stages and measures of hippocampus, corpus callosum and frontal cortex size.  Data were covaried by SES and measures of overall brain size (intracranial volume, midsagittal area, total gray matter volume).

Summary

Within the same group of subjects there were marked differences between regions in the stages of greatest vulnerability.  The hippocampus was particularly sensitive to abuse reported to occur at 3-5 and 11-13 years of age.  In contrast, the rostral body of the corpus callosum was affected by abuse reported to have occurred at ages 9-10, and prefrontal cortex by abuse at ages 14-16.

Discussion

Childhood abuse has been associated with vulnerability to a host of psychiatric disorders and behavioral problems. Based on the present findings, there may be different abuse-related syndromes associated with particular stages of abuse and specific regional brain changes.

Identifying sensitive periods may also provide insight into key ages at which stimulation or environmental enrichment may optimally benefit development of specific brain regions.

Support

Supported, in part, by RO1 awards from the National Institute of Mental Health (MH-53636, MH-66222) and National Institute of Drug Abuse (DA-016934, DA-017846) to MHT.

Advertisements