Alterations in Inhibition Underlying Treatment Effects and Recovery in PTSD

Abstract

Inhibitory deficits expressed as difficulty ignoring irrelevant stimuli in the pursuit of goal-directed behavior may be crucial in our understanding of information processing in posttraumatic stress disorder (PTSD) and may serve as a fundamental mechanism of the disorder. If inhibitory deficits underlie the cognitive abnormalities in PTSD, then inhibition should improve with treatment; however, no published studies have examined changes in inhibition following PTSD treatment. Evidence of inhibitory processes as central to extinction suggests that exposure-based treatments may act directly on the inhibitory deficits implicated in PTSD, with selective serotonin reuptake inhibitors (SSRIs) facilitating serotonergic neurotransmission to bring about neurochemical changes in the fear circuitry. Accordingly, the present study examined changes in inhibition at pre-and post-treatment in individuals with chronic PTSD. Two inhibitory measures, attentional blink, a task that examines the temporal sequence of inhibition, and prepulse inhibition of startle, a behavioral measure that indexes the strength of inhibition, were used to study inhibition pre- and post-treatment. Specifically, this study examined whether inhibition changes with 10 weeks of prolonged exposure, a variant of an exposure-based treatment, or sertraline, the best-studied SSRI, for chronic PTSD. Treatment modality and treatment responder were examined to ascertain whether they change inhibition differentially. In addition, pre-treatment inhibitory deficits were examined as a predictor of change in trauma-related symptoms. Finally, individual difference factors such as age, sex, and education were examined as predictors of changes in inhibition. Individuals who made greater improvements with prolonged exposure showed faster improvements in inhibition on the critical inhibitory lag of the attentional blink task than sertraline, showing a large effect for this interaction, and pointing to potentially different mechanisms of treatment response in PTSD. Related to this, better inhibitory functioning on PPI, with a large effect at trend level, was associated with better treatment response, consistent with prepulse inhibitory functioning potentially serving as pre-treatment biomarker for treatment response. Finally, age contributed to slower improvements in a critical inhibitory lag of the attentional blink task over time, suggesting older individuals are associated with making less changes in inhibitory processes. Thus, differential modulation in fundamental attentional inhibitory processes by treatment responders suggests differential specificity in how prolonged exposure and sertraline normalize inhibitory processes. Further, prolonged exposure and sertraline may use specific pathways in how they bring about therapeutic change, however ultimately converge on a final common pathway in reducing amygdala reactivity.