Impaired fear inhibition is a biomarker of PTSD but not depression

Abstract

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.

Conditioned Fear Acquisition and Generalization in Generalized Anxiety Disorder

“…Some previous differential conditioning studies in PD (Lissek et al, 2009) or PTSD (Jovanovic et al, 2009(Jovanovic et al, , 2010 suggest that these patients have difficulties in suppressing fear responses to the CS-(i.e., deficits in inhibition learning) but this question has not specifically been investigated in GAD (see Lissek et al, 2005). In any case, it must be noted that most previous studies conducted in this area do not provide a direct test of differences in inhibition learning (see Mineka & Oehlberg, 2008).…”

“…On the other hand, the fact that we repeated our analyses GAD participant with comorbidity provides a unique perspective on the possible effects of comorbidity on fear conditioning abnormalities, a topic which has received little attention so far. If we assume that comorbidity is an index of severity (i.e, that patients with comorbidity are generally more severe than non-comorbid ones), one interesting possibility is that these abnormalities may be significantly associated with severity (current symptom) rather than the presence/absence of the disorder, as seen in a recent study in PTSD patients (Jovanovic et al, 2010). Moreover, this would be in agreement with data showing that fear learning abnormalities are also present in other "non-anxiety" disorders such as schizophrenia (see Holt, Coombs, Zeidan, Goff, & Milad, 2012).…”

“…Impaired within-session fear extinction has been shown for individuals with panic disorder (PD; Michael, Blechert, Vriends, Margraf, & Wilhelm, 2007;Otto et al, 2014) or GAD (Pitman & Orr, 1986), whereas impaired extinction recall could be present in PTSD (Milad et al, 2008) or obsessive-compulsive disorder (OCD; Milad et al, 2013). Moreover, conditioned inhibition deficits may characterize PTSD (Jovanovic et al, 2009(Jovanovic et al, , 2010. However, these results have not been always replicated.…”

Learning not to Fear: Neural Correlates of Learned Safety

“…The training phase (left) consisted of four unpaired CS (B and X) alone (bottom row) and paired CS (A and X) presentations and the US (top row). The test phase (right) consisted of three presentations of the CS (A and B) (Jovanovic et al, 2010). (c) A cluster of differential activation in the left amygdala between safety and fear trained subjects in response to the CS is shown on a standard brain.…”

“…Mean fear-potentiated startle on AX þ , BX À , and AB trials across diagnostic groups from three studies. Fear-potentiated startle in a traumatized civilian sample with post-traumatic stress disorders (PTSD) (n ¼ 29) and without PTSD (n ¼ 61) (Jovanovic et al, 2010). Reproduced, with permission, from Jovanovic et al (2010) and Pollak et al (2010b) …”