PEDIATRICS Vol. 120 No. 1 July 2007, pp. 234-235 (doi:10.1542/peds.2007-1024)
LETTER TO THE EDITOR |
Stressing About Posttraumatic Stress Disorder: In Reply
Victor G. Carrion, MDDepartment of Psychiatry and Behavioral Sciences
Stanford University
Stanford, CA 94305
Carl F. Weems, PhD
Department of Psychology
University of New Orleans
New Orleans, LA 70148
Allan L. Reiss, MD
Department of Psychiatry and Behavioral Sciences
Stanford University
Stanford, CA 94305
Drs Steen and Hamer raise 5 questions about our recent article in Pediatrics1: (1) the reliability of the hippocampus measurement; (2) sample size; (3) lack of a control group; (4) the number and type of statistical tests; and (5) the theoretical implications of its consistency with 1 of 2 competing hypotheses. We appreciate their interest in our work and address each of these issues below.
Regarding the issue of hippocampal reliability, we had strong interrater reliability with a 0.95 intraclass correlation coefficient. Our laboratory has published on hippocampal measurement approaches to address the inherent challenges of measuring small volumes (see ref 2). Imaging studies can always be affected by software and hardware; however, our laboratory has maintained backward compatibility with previous scanning techniques, and we routinely examine the effects of hardware or major software upgrades on image quality and characteristics to understand if there are any changes. We use the same scanner hardware and identical pulse sequences and software processing techniques. For example, we exclude scans that are technically unacceptable because of motion or other artifacts.
The second issue addresses sample size. We agree that any study can be improved with a larger sample size. Recognizing the limitation, we called it a pilot study. Steen and Hamer, however, raise the issue of power. Their comments do not apply to our findings, because the effect size obtained was large enough to meet the criteria set for statistical significance in the study. Their comments, however, do provide an important suggestion for future work in this area, specifically, that larger sample sizes and power may be particularly important for studies that attempt to replicate these findings in the future. In our article we stressed that our conclusions were "limited by the sample size" and that "findings should be considered preliminary until replicated."
We agree with Steen and Hamer that performing this study with controls would have strengthened the results. As we mentioned in our article, however, our goal was to study the pathogenesis of hippocampal reduction in this sample and not to compare how hippocampal volume may differ between clinical and nonclinical groups. We have reported that in terms of functional impairment, there is no significant difference between children with posttraumatic stress disorder (PTSD) and children with subthreshold posttraumatic reactions.3 Studying the natural continuum of symptoms in traumatized youth and how it may impact brain development have been some of our goals.
The fourth issue is the statistical approach. We carefully explained in the article why we chose the statistical approach we took. We disagree that intraclass or concordance correlations would have been more appropriate, because we were attempting to establish the association between cortisol and PTSD symptoms and hippocampal change; we were not trying to show that PTSD and cortisol are "invariant in terms of mean and SD."
Steen and Hamer also mentioned potential error caused by the multiple correlations presented in our Table 2 (type 1 error). The multiple tests were not probes for a significant finding among a host of possible associations but, rather, were theoretically directed tests. At least 20 of the 24 correlations presented in Table 2 were provided for completeness or descriptive or exploratory purposes only. What we find remarkable, from a theoretical perspective, was that both cortisol levels and PTSD symptoms at time 1 were associated with change in hippocampal volumes. If only PTSD symptoms or only cortisol levels were associated with change in hippocampal volumes, a chance association would seem more likely; however, this was not the case.
We note again that we made it clear in the discussion section of our article that ours was preliminary evidence and that larger studies are needed to confirm these findings and clarify the role that additional factors may play in this association. However, given the difficulty in conducting and obtaining funding for such studies without any evidence, we feel that our study was an important contribution at this point in the development of the literature, because it points to the need for such larger studies.
On their last point, Steen and Hamer cite 2 studies: one by DeBellis et al4 and another by our group.5 We would like to clarify their comments on these studies because, as presented, they can be misconstrued. In the DeBellis et al article, there were only 9 subjects with PTSD; the addition of 9 controls made it an 18-subject study. Our article, which showed no hippocampal differences, was a cross-sectional study. As we mentioned in the introduction of the article, neither we nor DeBellis et al have found hippocampal differences when conducting cross-sectional studies. Two pediatric longitudinal studies have found either no hippocampal difference or a hippocampal reduction associated with cortisol and PTSD symptoms. The 2 approaches used by these 2 studies provided interesting leads into the study of hippocampal development and PTSD. Like any other subject in science, the ultimate answer to these questions relies on replication.
We hope our findings prompt large-scale investigations and serve as a basis for future exploration in this area.
REFERENCES
- Carrion VG, Weems CF, Reiss AL. Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus.
Pediatrics. 2007;119
:509
–516
[Abstract/Free Full Text] - Kates WR, Abrams MT, Kaufmann WE, Breiter SN, Reiss AL. Reliability and validity of MRI measurement of the amygdala and the hippocampus in children with fragile X syndrome. Psychiatry Res. 1997;75 :31 –48[Web of Science][Medline]
- Carrion VG, Weems CF, Ray R, Reiss AL. Toward an empirical definition of pediatric PTSD: the phenomenology of PTSD symptoms in youth. J Am Acad Child Adolesc Psychiatry. 2002;41 :166 –173[CrossRef][Web of Science][Medline]
- De Bellis MD, Hall J, Boring AM, Frustaci K, Moritz G. A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry. 2001;50 :305 –309[CrossRef][Web of Science][Medline]
- Carrion VG, Weems CF, Eliez S, et al. Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder. Biol Psychiatry. 2001;50 :943 –951[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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