Background A central problem in posttraumatic stress disorder (PTSD) is a reduced capacity to suppress fear under safe conditions. Previously, we have shown that combat-related PTSD patients have impaired inhibition of fear-potentiated startle. Given the high comorbidity between PTSD and depression, our goal was to see whether this impairment is specific to PTSD, or a nonspecific symptom associated with both disorders. Methods Fear-potentiated startle (FPS) was assessed in 106 trauma-exposed individuals divided into four groups: a) No diagnosis control, b) PTSD only, c) major depression (MDD) only, and d) comorbid PTSD and MDD. We used a novel conditional discrimination procedure, in which one set of shapes (the danger signal) was paired with aversive airblasts to the throat, and different shapes (the safety signal) were presented without airblasts. The paradigm also included fear inhibition transfer test. Results Subjects with comorbid MDD and PTSD had higher FPS to the safety signal and to the transfer test compared to controls and MDD only subjects. In contrast to the control and MDD groups, the PTSD and comorbid PTSD and MDD groups did not show fear inhibition to safety cues. Conclusions These results suggest that impaired fear inhibition may be a specific biomarker of PTSD symptoms.

Understanding the neurobiological correlates of childhood maltreatment is critical to delineating stress-related psychopathology. The acoustic startle response (ASR) is a subcortical reflex modulated by neural systems implicated in posttraumatic stress disorder (PTSD). ASR is conserved across species and is increased in rodent models of developmental stress. measured acoustic startle response to a 40ms noise probe as well as fear-potentiated startle using electromyographic (EMG) recordings of the eyeblink in a primarily African-American sample (N=60) from a highly traumatized civilian population. We assessed self-reported history of abuse with the Childhood Trauma Questionnaire and current symptoms with the PTSD Symptom Scale and the Beck Depression Inventory. We found that subjects reporting a history of high levels of physical or sexual abuse had increased startle on all trial types relative to those with low abuse (p<.01). This effect remained significant after co-varying for the subjects’ age and sex, as well as PTSD and depression symptoms. Perceived childhood sexual abuse was the greatest predictor of increased startle response. Notably, emotional abuse in childhood did not affect baseline startle, and all groups demonstrated equivalent levels of fear-potentiated startle. The long-lasting effects of early life trauma result in increased risk for adult psychopathology. These new data demonstrate that a self-report history of child abuse is related to altered baseline startle response that is not accounted for by PTSD or depression symptoms. Increased startle may be a biomarker of stress responsiveness that can be a persevering consequence of early trauma exposure during childhood.