Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28% P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.

BackgroundPosttraumatic stress disorder (PTSD) following childbirth has gained growing attention in the recent years. Although a number of predictors for PTSD following childbirth have been identified (e.g., history of sexual trauma, emergency caesarean section, low social support), only very few studies have tested predictors derived from current theoretical models of the disorder. This study first aimed to replicate the association of PTSD symptoms after childbirth with predictors identified in earlier research. Second, cognitive predictors derived from Ehlers and Clark’s (2000) model of PTSD were examined.MethodsN = 224 women who had recently given birth completed an online survey. In addition to computing single correlations between PTSD symptom severities and variables of interest, in a hierarchical multiple regression analyses posttraumatic stress symptoms were predicted by (1) prenatal variables, (2) birth-related variables, (3) postnatal social support, and (4) cognitive variables.ResultsWellbeing during pregnancy and age were the only prenatal variables contributing significantly to the explanation of PTSD symptoms in the first step of the regression analysis. In the second step, the birth-related variables peritraumatic emotions and wellbeing during childbed significantly increased the explanation of variance. Despite showing significant bivariate correlations, social support entered in the third step did not predict PTSD symptom severities over and above the variables included in the first two steps. However, with the exception of peritraumatic dissociation all cognitive variables emerged as powerful predictors and increased the amount of variance explained from 43% to a total amount of 68%.ConclusionsThe findings suggest that the prediction of PTSD following childbirth can be improved by focusing on variables derived from a current theoretical model of the disorder.

In the current review, we reconceptualize a categorical diagnosis-panic disorder and agoraphobia-in terms of two constructs within the domain "negative valence systems" suggested by the Research Domain Criteria initiative. Panic attacks are considered as abrupt and intense fear responses to acute threat arising from inside the body, while anxious apprehension refers to anxiety responses to potential harm and more distant or uncertain threat. Taking a dimensional view, panic disorder with agoraphobia is defined with the threat-imminence model stating that defensive responses are dynamically organized along the dimension of the proximity of the threat. We tested this model within a large group of patients with panic disorder and agoraphobia (N = 369 and N = 124 in a replication sample) and found evidence that panic attacks are indeed instances of circa strike defense. This component of the defensive reactivity was related to genetic modulators within the serotonergic system. In contrast, anxious apprehension-characterized by attentive freezing during postencounter defense-was related to general distress and depressive mood, as well as to genetic modulations within the hypothalamic-pituitary-adrenal (HPA) axis. Patients with a strong behavioral tendency for active and passive avoidance responded better to exposure treatment if the therapist guides the patient through the exposure exercises.

This meta-analysis examined three variables of emotional processing theory (EPT). Initial fear activation was not linearly related to outcomes of exposure therapy. Habituation within and between sessions were shown to correlate with outcome. Outcome reporting bias was shown to play a crucial role in this meta-analysis. Results do not specifically support EPT.

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