Determinants of quality of life improvements in anxiety and depressive disorders-A longitudinal study of inpatient psychotherapy.

Background: Quality of life (QoL) is substantially impaired in patients with anxiety disorders (AD) and depressive disorders (DD) and improvements in symptom burden after psychotherapy are not always paralleled by similar improvements in QoL. So far, little is known about treatment outcome in terms of QoL and predictors of QoL improvements following inpatient psychotherapy with a focus on cognitive behavior therapy (CBT). The current study aimed at investigating the relationship between changes in symptoms and QoL across different life domains. Additionally, predictors of a positive treatment outcome were evaluated. Methods: 122 patients with AD and/or DD undergoing an 8-weeks inpatient CBT program completed self-report measures of psychopathological symptoms and QoL at pre- and post-treatment. Mixed effects models were used to investigate changes, a confirmatory factor analysis was applied to analyze the latent factor structure of the anxiety sensitivity index and binary logistic regression analyses were performed for predictors of QoL improvements. Results: Patients showed moderate to strong decreases in anxious and depressive symptoms and moderate to strong improvements in general QoL, particularly in the psychological and physical QoL subdomains. Changes in symptom burden correlated most strongly with psychological and physical QoL. In addition, poor QoL before treatment and low levels of specific anxiety sensitivity symptoms (items 1 and 5) significantly predicted improvement in QoL. Conclusion: Patients with poor QoL who are not as inhibited to openly express their anxious feelings particularly benefit from inpatient psychotherapy (individual and group) to improve their QoL. In contrast, our research suggests that patients who are too anxious to openly express their nervousness should receive additional social skills training, more focused treatment to build sufficient self-confidence to better engage in the treatment program.

Peritraumatic unconditioned and conditioned responding explains sex differences in intrusions after analogue trauma.

Higher prevalence of posttraumatic stress disorder (PTSD) in women than men may be explained by sex differences in fear learning processes. Initial evidence points to elevated unconditioned and conditioned fear responding as well as to elevated state anxiety in women as potential peritraumatic mechanisms. Using the "conditioned-intrusion-paradigm", which combines differential fear conditioning with the trauma-film paradigm, neutral sounds were presented as predictors of the occurrence (CS+) or non-occurrence (CS-) of highly aversive films. Intrusions were elicited by these sounds in the laboratory after conditioning and naturalistic intrusions were assessed in daily-life on subsequent days. Compared to men (n = 62), women (n = 60) reported more intrusions and associated distress following analogue trauma. Sex differences in intrusive symptoms were mediated by a) higher unconditioned trauma responding, b) slowed extinction of differential CS valence ratings, and c) elevated state anxiety increase across conditioning in women. Secondary analyses revealed that state anxiety was the strongest mediator, followed by slowed extinction learning. Mediation models were unrelated to sex differences in trait anxiety or depressive symptoms. Thus, associative (extinction learning) and non-associative (state anxiety, trauma responding) mechanisms contribute to sex differences in intrusive symptoms after analogue trauma and might add to the heightened vulnerability to PTSD in women.

Neural activity during traumatic film viewing is linked to endogenous estradiol and hormonal contraception.

Women are at higher risk for Posttraumatic Stress Disorder (PTSD) and recent research has highlighted a modulating role of female sex hormones for cognitive and emotional processes potentially underlying PTSD symptoms. However, studies combining fMRI recordings of brain activity during trauma film viewing with assessment of female sex hormones are missing. The trauma film paradigm - a widely used experimental analogue for trauma exposure - confronts healthy participants with traumatic film clips and thus allows studying peritraumatic processing under laboratory conditions. Following this paradigm, the current fMRI study examined the role of endogenous estradiol and synthetic sex hormones for the neural processing of traumatic (i.e., depicting interpersonal violence) vs. neutral films in 53 healthy women (mean age 22.3 years; 23 using hormonal contraception, HC). As predicted, traumatic films strongly activated areas of the fear processing network, such as amygdala, insula, and dorsal anterior cingulate cortex. Estradiol levels in women not using HC were positively correlated with ventromedial prefrontal activity. Furthermore, women using HC as compared to women without HC demonstrated heightened insula and dorsal anterior cingulate cortex activity during traumatic film viewing. These experimental results highlight the effects of both gonadal hormone status and HC intake on peritraumatic processing in neural regions relevant for emotion generation and regulation that have been found to be abnormal in PTSD.

Attend or defend? Sex differences in behavioral, autonomic, and respiratory response patterns to emotion-eliciting films.

Sex differences in emotional reactivity have been studied primarily for negative but less so for positive stimuli; likewise, sex differences in the psychophysiological response-patterning during such stimuli are poorly understood. Thus, the present study examined sex differences in response to negative/positive and high/low arousing films (classified as threat-, loss-, achievement-, and recreation-related, vs. neutral films), while measuring 18 muscular, autonomic, and respiratory parameters. Sex differences emerged for all films, but were most prominent for threat-related films: Despite equivalent valence and arousal ratings, women displayed more facial-muscular and respiratory responding than men and pronounced sympathetic activation (preejection period, other cardiovascular and electrodermal measures), while men showed coactivated sympathetic/parasympathetic responding (including increased respiratory sinus arrhythmia). This indicates a prototypical threat-related defense response in women, while men showed a pattern of sustained orienting, which can be understood as a shift toward less threat proximity in the defense cascade model. Clinical implications are discussed within a socio-evolutionary framework.

Low levels of estradiol are associated with elevated conditioned responding during fear extinction and with intrusive memories in daily life.

Posttraumatic stress disorder (PTSD) can be conceptualized as a disorder of emotional memory showing strong (conditioned) responses to trauma reminders and intrusive memories among other symptoms. Women are at greater risk of developing PTSD than men. Recent studies have demonstrated an influence of ovarian steroid hormones in both fear conditioning and intrusive memory paradigms. However, although intrusive memories are considered non-extinguished emotional reactions to trauma reminders, none of the previous studies has investigated effects of ovarian hormones on fear conditioning mechanisms and intrusive memories in conjunction. This may have contributed to an overall inconsistent picture of the role of these hormones in emotional learning and memory. To remedy this, we exposed 37 healthy women with a natural menstrual cycle (during early follicular or luteal cycle phase) to a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with short violent film clips as unconditioned stimuli. Intrusive memories about the film clips were assessed ambulatorily on subsequent days. Women with lower levels of estradiol displayed elevated differential conditioned skin conductance responding during fear extinction and showed stronger intrusive memories. The inverse relationship between estradiol and intrusive memories was at least partially accounted for by the conditioned responding observed during fear extinction. Progesterone levels were not associated with either fear acquisition/extinction or with intrusive memories. This suggests that lower levels of estradiol might promote stronger symptoms of PTSD through associative processes.

Relationship between fear conditionability and aversive memories: evidence from a novel conditioned-intrusion paradigm.

Intrusive memories--a hallmark symptom of posttraumatic stress disorder (PTSD)--are often triggered by stimuli possessing similarity with cues that predicted or accompanied the traumatic event. According to learning theories, intrusive memories can be seen as a conditioned response to trauma reminders. However, direct laboratory evidence for the link between fear conditionability and intrusive memories is missing. Furthermore, fear conditioning studies have predominantly relied on standardized aversive stimuli (e.g. electric stimulation) that bear little resemblance to typical traumatic events. To investigate the general relationship between fear conditionability and aversive memories, we tested 66 mentally healthy females in a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with neutral sounds as conditioned stimuli and short violent film clips as unconditioned stimuli. Subsequent aversive memories were assessed through a memory triggering task (within 30 minutes, in the laboratory) and ambulatory assessment (involuntary aversive memories in the 2 days following the experiment). Skin conductance responses and subjective ratings demonstrated successful differential conditioning indicating that naturalistic aversive film stimuli can be used in a fear conditioning experiment. Furthermore, aversive memories were elicited in response to the conditioned stimuli during the memory triggering task and also occurred in the 2 days following the experiment. Importantly, participants who displayed higher conditionability showed more aversive memories during the memory triggering task and during ambulatory assessment. This suggests that fear conditioning constitutes an important source of persistent aversive memories. Implications for PTSD and its treatment are discussed.