The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD).

BACKGROUND: Studies using structural magnetic resonance imaging (MRI) volumetrics showed smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD). These studies were cross-sectional and did not address whether smaller volume is secondary to stress-induced damage, or whether pre-existing factors account for the findings. The purpose of this study was to use a co-twin case control design to assess the relative contribution of genetic and environmental factors to hippocampal volume in PTSD. METHODS: Monozygotic (N = 13 pairs) and dizygotic (N = 21 pairs) twins with a history of Vietnam Era military service, where one brother went to Vietnam and developed PTSD, while his brother did not go to Vietnam or develop PTSD, underwent MR imaging of the brain. Structural MRI scans were used to manually outline the left and right hippocampus on multiple coronal slices, add the areas and adjust for slice thickness to determine hippocampal volume. RESULTS: Twins with Vietnam combat-related PTSD had a mean 11% smaller right hippocampal volume in comparison to their twin brothers without combat exposure or PTSD (p < .05). There was no significant interaction by zygosity, suggesting that this was not a predisposing risk factor or genetic effect. CONCLUSIONS: These findings are consistent with smaller hippocampal volume in PTSD, and suggest that the effects are primarily due to environmental effects such as the stress of combat.

Serotonin transporter gene, depressive symptoms, and interleukin-6.

BACKGROUND: We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels. METHODS AND RESULTS: We genotyped 20 polymorphisms in 360 male twins (mean age, 54 years) from the Vietnam Era Twin Registry. Current depressive symptoms were measured with the Beck Depression Inventory II. IL-6 was assessed using a commercially available ELISA kit. Genotype associations were analyzed using generalized estimating equations. To study how SLC6A4 genetic vulnerability influences the relationship between depressive symptoms and IL-6, bivariate models were constructed using structural equation modeling. Of the 20 polymorphisms examined, the effective number of independent tests was 6, and the threshold of significance after Bonferroni correction was 0.008. There were 6 single-nucleotide polymorphisms significantly associated with Beck Depression Inventory (P< or =0.008), including rs8071667, rs2020936, rs25528, rs6354, rs11080122, and rs8076005, and 1 single-nucleotide polymorphism was borderline associated (rs12150214, P=0.017). Of these 7 single-nucleotide polymorphisms, 3 were also significantly associated with IL-6 (P<0.008), including rs25528, rs6354, and rs8076005, and the other 4 were borderline associated (P=0.009 to 0.025). The subjects with 1 copy of the minor allele of these 7 single-nucleotide polymorphisms had higher Beck Depression Inventory scores and IL-6 levels. Further bivariate modeling revealed that approximately 10% of the correlation between Beck Depression Inventory and IL-6 could be explained by the SLC6A4 gene. CONCLUSIONS: Genetic vulnerability involving the SLC6A4 gene is significantly associated with both increased depressive symptoms and elevated IL-6 plasma levels. Common pathophysiological processes may link depression and inflammation, and implicate the serotonin pathway in neural-immune interactions.