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Immune-Related Gene Expression Linked to PTSD in Nepali Child Soldiers

NEW YORK (GenomeWeb) – A new study of former child soldiers in Nepal has found that expression of an immune-related gene regulatory network is linked to measures of post-traumatic stress disorder severity. The results corroborate studies of the effects of childhood stress on gene expression performed in Western, educated, industrialized, rich, and democratic countries, and give credence to the idea that psychological "resilience" can mitigate molecular consequences of stress, the authors said.

Scientists from several universities — led by Duke University medical anthropologist Brandon Kohrt and University of California, Los Angeles psychiatry Professor Steven Cole — studied gene expression profiles of a non-Western population comprised of former child soldiers and civilian controls from Nepal. Specifically, they looked at the conserved transcriptional response to adversity (CTRA) gene regulatory network. Previous studies had found associations between chronic exposure to stress, up-regulation of pro-inflammatory genes, and down-regulation of anti-viral genes.

Using RNA extracted from dried blood spots and gene expression profiling using Illumina BeadChips, the scientists paired CTRA expression profiles with data on PTSD severity as well as how "resilient" the individuals perceived themselves to be, as measured by a questionnaire.

"CTRA gene expression profiles were linked to the degree of trauma exposure and associated distress, as measured by PTSD symptom severity above a culturally and clinically validated cutoff point, more than to child soldier status per se," the authors wrote today in the Proceedings of the National Academy of Sciences.

Data for the study was collected as part of a longitudinal investigation led by Kohrt on the mental health of child soldiers — it began in 2007 after peace accords ended a decade-long civil war in Nepal.

Of an initial cohort of 258 former child soldiers, dried blood spots were available for 154. The PNAS study also included 136 matched non-soldiers. PTSD was diagnosed in 25 child soldiers (16 percent) and 8 controls (6 percent). At the time of enrollment, the average age of the former child soldiers was just over 15 years old, with a range of 11 to 17 years old. At the time the blood spots were taken in 2012, the average age was just over 20 years old.

While 254 of the participants (90 percent) yielded valid transcriptome profiles, the authors noted that dried blood spot samples did not yield sufficient quantities of RNA to perform a direct assessment of RNA integrity by capillary electrophoresis or other methods. "As such, all available DBS samples were submitted to assay, and sample validity was assessed using an assay endpoint criterion based on the distribution of hybridization fluorescence intensity values," the researchers wrote.

They also noted that despite coming out of a social context that prioritizes the collective group rather than the individual, that former child soldiers with higher scores of self-perceived "resilience" showed gene expression profiles similar to non-soldiers without PTSD.

"These results suggest that CTRA responses to early life social adversity may represent a relatively broad human potential," the authors noted.

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