Unique Environmental and Familial Influence on Amygdalar Hyperresponsivity in Posttraumatic Stress Disorder: A Discordant Monozygotic Twin Study.

BACKGROUND

The partially genetic nature of posttraumatic stress disorder (PTSD) has been demonstrated in both twin and recent molecular genetics studies and complicates the assessment of unique environmental influence on altered phenotypes in PTSD. Previous functional neuroimaging studies have reported heightened amygdalar responsivity in PTSD, but whether this abnormality relates to familial factors or PTSD-triggering environmental experiences is not fully understood.

METHODS

We examined amygdalar responsivity in combat veterans with PTSD and their combat-unexposed monozygotic co-twins (20 individuals, PTSD group n = 10), as well as in combat veterans without PTSD and their combat-unexposed co-twins (32 individuals, non-PTSD group n = 16). Within-pair comparisons were performed to isolate unique environmental influence under strict control of genetic factors. Comparisons between the unexposed co-twins of both groups were conducted to test for effects of familial vulnerability.

RESULTS

Reflecting unique environmental influence, heightened amygdalar responsivity was observed in individuals with PTSD compared with their unaffected co-twins. This was associated with the expression patterns of genes involved in brain glutamatergic synaptic transmission. Reflecting familial vulnerability, unexposed co-twins of combat veterans with PTSD showed reduced amygdalar activation compared with unexposed co-twins of combat veterans without PTSD.

CONCLUSIONS

Heightened amygdalar responsivity in PTSD is best explained by an interaction of unique environmental and familial influences, which is consistent with vulnerability-stress models.