Method and Participants

Subjects selected for study were right-handed, healthy, unmedicated young adults (18 to 22 years of age), with excellent hearing and visual acuity, recruited from the community by advertisements targeted toward college students. They were selected based on (a) a complete absence of exposure to trauma or (b) a self-reported history of exposure to repeated childhood sexual abuse (CSA, defined as at least three episodes of forced sexual contact accompanied by threats of harm to self or others and feelings of fear or terror, which occurred before age 18 years and at least 2 years prior to enrollment). Subjects were excluded who had any history of substance abuse, any recent substance use, brain injury with loss of consciousness, significant fetal exposure to alcohol or drugs, perinatal or neonatal complications, neurological disorders, or medical conditions that could adversely affect growth and development. Control subjects had no history of Axis I psychopathology (DSM-IV). The McLean Hospital Institutional Review Board approved all procedures. The purpose and meaning of this study were explained to subjects, who gave their written informed consent. Screenings were conducted on 720 volunteers to recruit 30 subjects with CSA and 30 control subjects for MRI evaluation. A disproportionate number of subjects with CSA were female. Hence, we limited this study to 23 females with CSA (mean age = 19.1 years; SD = 1.1 years) and to 14 female control subjects (mean age = 20.1 years; SD = 1.3 years) with complete MRI scans. The detailed selection process is published elsewhere (Navalta et al., 2006).

Four subjects with CSA had current major depressive disorder (MDD), 4 had post-traumatic stress disorder (PTSD), and 1 had depersonalization disorder. Abuse and control subjects were predominantly middle class or higher (96%); both groups had similar measures of parental socioeconomic status (SES; Hollingshead, 1975; F[1, 35] = 0.35, p = .26), and cognitive abilities as evaluated using the Memory Assessment Scale (MAS; Williams, 1991; global memory = 117 ± 10.1 versus 114 ± 14.2; F[1, 35] = 0.36, p = .46), and subjects' reports of Scholastic Aptitude Test (SAT) scores (scores = 1246 ± 145 versus 1299 ± 103; F[1, 29] = 2.1, p = .26).

MRI images were acquired on a General Electric Medical Systems (Milwaukee, WI) 1.5T Horizon LX Echo Speed scanner (Level 8.4) with a prototype Pathway MRI quadrature, receive-only, volume head coil. The Pathway coil provides an approximately 35% improvement in signal-to-noise ratio over the standard quadrature head coil. The anatomical image series consisted of T1-weighted sagittals, T2-weighted sagittals, T2-weighted axials, volumetric T1-weighted coronals, and anatomical dual echo axials (proton and T2-weighted). Parameters for the volumetric T1-weighted coronal images were three-dimensional, Fourier transform, spoiled gradient recalled acquisition (3DFT, SPGR) pulse sequence (TR = 35, TE = 5 ms/Fr; Flip angle = 45 degrees, FOV = 22 x 16 cm, 1.5 mm slice with no skip, 256 x 192 matrix, 1 NEX). Voxel-based morphometry (VBM) was performed using SPM2 for imaging processing (Ashburner & Friston, 2000; Good et al., 2001; Okada, Tanaka, Kuratsune, Watanabe, & Sadato, 2004) running in MATLAB 6.5 (The MathWorks Inc., Natick, MA, USA). VBM is a fully automated whole-brain mor-phometric technique that detects regional structural differences between groups on a voxel-by-voxel basis. Briefly, images were segmented into gray matter, white matter, cerebrospinal fluid, and skull/scalp compartments, then normalized to standard space and resegmented. Any volume changes induced by normalization were adjusted. The spatially normalized segments of gray and white matter were smoothed using a 12 mm, full-width, half-maximum, isotropic Gaussian kernel. Statistical analysis of regional differences between groups was performed using a permutation test for decreased probability of a particular voxel containing gray or white matter. Potential confounding effects of SES and whole segment gray matter volume (GMV) differences were modeled. Variances attributable to them were excluded from analysis. The significance levels for statistics estimated by permutation tests were set at p < 0.05, corrected for multiple comparisons. Within the areas showing a significant volume reduction in subjects, linear correlates between volume reduction and the neuropsychiatric assessment and evaluation of neuropsychological and cognitive functions were examined under the threshold of p < 0.001 to compensate for multiple comparisons. VBM is a potentially powerful technique for identifying morphometric differences between groups, but hinges on a number of assumptions, particularly the accuracy of image coregistration (Bookstein, 2001).

Psychometric evaluation included the Structured Clinical Interview for DSM-IV (First, Spitzer, Gibbon, & Williams, 1997) for diagnoses of MDD, PTSD, and other psychiatric disorders. We also administered the MAS (Williams, 1991), which comprises 12 subtests based on the following seven memory tasks: verbal span, verbal list learning, verbal prose memory, visual span, visual recognition, visual reproduction, and names-faces (a verbal-visual, paired-associates task). The resultant global memory and summary scale scores provided measures of overall memory performance, short-term memory, verbal memory, and visual memory.

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