Effect of PTSD treatment on cardiovascular reactivity during trauma memory recall and correspondence with symptom improvement.

ABSTRACTBackground: Prior research has shown PTSD treatment leads to reductions in cardiovascular reactivity during trauma recall, but the extent to which such reductions are associated with changes in PTSD symptoms is less clear. Moreover, such relationships have not been investigated in a cognitively focused PTSD treatment.Objective: To examine changes in cardiovascular reactivity to the trauma memory in patients receiving cognitive processing therapy (CPT), CPT with a written trauma account, and a written account only condition. We also examined the association of such changes with symptom improvement.Method: 118 women with PTSD secondary to interpersonal violence completed pre- and post-treatment assessments of PTSD symptoms and cardiovascular reactivity during a script-driven imagery task.Results: Results indicated a significant but modest reduction in cardiovascular reactivity in CPT conditions. Changes in cardiovascular reactivity and reexperiencing symptoms were significantly associated among the whole sample. Among individuals with the greatest reactivity to the trauma memory at pretreatment, associations were also seen with changes in total PTSD, numbing, and trauma-related guilt.Conclusions: Results indicate that previous findings on the effect of PTSD treatment on cardiovascular reactivity during trauma recall extend to cognitively oriented treatment. Baseline cardiovascular reactivity may influence the extent to which reductions in PTSD symptoms and reactivity during trauma recall are related.

Cognitive Processing Therapy leads to reduced heart rate reactivity when recalling a trauma memory.Decreases in heart rate reactivity are associated with reduced reexperiencing symptoms.Changes in heart rate reactivity and PTSD symptoms are more closely related among patients with greater pretreatment reactivity.

Heart rate reactivity during trauma recall as a predictor of treatment outcome in cognitive processing therapy for PTSD.

Emotional engagement when recollecting a trauma memory is considered a key element of effective trauma-focused therapy. Research has shown that reduced physiological reactivity during trauma recall is associated with worse treatment outcomes for posttraumatic stress disorder (PTSD), but this has yet to be examined in a cognitively oriented treatment. This study examined whether pretreatment heart rate (HR) reactivity during trauma recall predicts PTSD symptom improvement and treatment dropout during Cognitive Processing Therapy (CPT) for PTSD. Participants were 142 women with PTSD secondary to interpersonal violence enrolled in one of two clinicals trials. HR reactivity reflected the mean increase in HR after listening to two 30-s scripts of the trauma memory prior to treatment. Linear mixed-effects models showed the effect of HR reactivity on change in total PTSD symptoms was not significant, but lower HR reactivity predicted less improvement in reexperiencing and avoidance and was associated with increased dropout. Findings suggest pretreatment physiological reactivity to the trauma memory may be a prognostic indicator of some elements of treatment response in CPT. Results tentatively support the importance of emotional activation during trauma recall in cognitive treatment of PTSD, though more research is needed to clarify how low HR reactivity impacts treatment.

The associations between repetitive negative thinking, insomnia symptoms, and sleep quality in adults with a history of trauma.

BACKGROUND: Posttraumatic stress disorder (PTSD) and sleep disturbance are highly comorbid and repetitive negative thinking (RNT) is associated with both sleep disturbance and PTSD. However, few studies have examined the association between RNT and sleep disturbance in individuals exposed to trauma, with and without PTSD. METHOD: Associations between trait-level and trauma-related RNT, insomnia, and sleep quality were investigated in a trauma-exposed MTurk (N = 342) sample. Additionally, PTSD symptom severity was tested as a moderator of the associations between RNT and insomnia and sleep quality. RESULTS: Trait-level RNT predicted poorer sleep quality and greater insomnia, regardless of PTSD severity. Trauma-related RNT was also associated with greater insomnia, though the effect was moderated by PTSD severity such that it was significant for participants with low and moderate, but not severe, PTSD. Both trait- and trauma-related RNT were associated with several specific aspects of sleep quality, including: sleep disturbances, daytime dysfunction, use of sleep medications, sleep onset latency, and subjective sleep quality. CONCLUSIONS: This study demonstrates significant associations linking RNT with insomnia and sleep disturbance in trauma-exposed individuals. Clinically, results suggest that it may be helpful to target both general and trauma-related RNT in sleep interventions for trauma-exposed individuals with insomnia.

Tobacco withdrawal-induced changes in sensorimotor filtering as a predictor of smoking lapse in trauma-exposed individuals.

Prepulse inhibition (PPI) is a measure of sensorimotor filtering thought to shield the processing of initial weaker auditory stimuli from interruption by a later startle response. Previous studies have shown smoking withdrawal to have a negative impact on sensorimotor filtering, particularly in individuals with psychopathology. Because tobacco use may alleviate sensory and sensorimotor filtering deficits, we examined whether smoking withdrawal-induced changes in PPI were associated with maintenance of smoking abstinence in trauma-exposed individuals with and without PTSD who were attempting to quit smoking. Thirty-eight individuals (n = 24 with current or past PTSD; 14 trauma-exposed healthy controls) made an acute biochemically-verified smoking cessation attempt supported by 8 days of contingency management (CM) and cognitive behavioral therapy (CBT) for smoking. Participants completed a PPI task at the pre-quit baseline, 2 days post-quit, and 5 days post-quit. Post-quit changes in PPI were compared between those who remained abstinent for the first 8-days of the quit attempt and those who lapsed back to smoking. PPI changes induced by biochemically-verified smoking abstinence were associated with maintenance of abstinence across the 8-day CM/CBT-supported quit attempt. As compared to those who maintained tobacco abstinence, participants who lapsed to smoking had significantly lower PPI at 2 and 5 days post-quit relative to baseline. Thus, among trauma-exposed individuals, decreases in PPI during acute smoking cessation supported by CM/CBT are associated with lapse back to smoking. Interventions that improve PPI during early smoking abstinence may facilitate smoking cessation among such individuals who are at high risk for chronic, refractory tobacco use.

The transition to civilian life: Impact of comorbid PTSD, chronic pain, and sleep disturbance on veterans' social functioning and suicidal ideation.

OBJECTIVE: Trauma-exposed veterans may be more likely to experience posttraumatic stress disorder (PTSD), chronic pain, and sleep disturbance together rather than in isolation. Although these conditions are independently associated with distress and impairment, how they relate to social functioning and suicidal ideation (SI) when experienced comorbidly is not clear. METHOD: Using longitudinal data on 5,461 trauma-exposed U.S. veterans from The Veterans Metrics Initiative study and self-reported disorders, we assessed (a) the extent to which PTSD co-occurs with sleep disturbance and chronic pain (CP); (b) the relationship of PTSD in conjunction with sleep disturbance and chronic pain with later social functioning and SI; and (c) the extent to which social functioning mediates the impact of multimorbidity on SI. RESULTS: At approximately 15 months postseparation, 90.5% of veterans with probable PTSD also reported sleep disturbance and/or CP. Relative to veterans without probable PTSD, veterans with all 3 conditions (n = 907) experienced the poorest social functioning (B = -.56, p < .001) and had greater risk for SI (OR = 3.78, p < .001); Social functioning partially mediated the relationship between multimorbidity and SI. However, relative to those with PTSD alone, sleep disturbance and CP did not confer greater risk for SI. CONCLUSIONS: Although these findings underscore the impact of PTSD on functioning and SI, they also highlight the complexity of multimorbidity and the importance of bolstering social functioning for veterans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Conditioned physiological reactivity and PTSD symptoms across the menstrual cycle: Anxiety sensitivity as a moderator.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is often associated with heightened physiological reactivity during fear conditioning procedures, but results vary across studies. This study examined whether anxiety sensitivity (AS), or the fear of arousal-related sensations, strengthens the relationship between PTSD symptoms and skin conductance responses (SCR) during fear conditioning and extinction. Because gonadal hormones implicated in fear learning fluctuate across the menstrual cycle, the stability of these relationships in women was examined in 2 distinct menstrual cycle phases. METHOD: Thirty-two trauma-exposed women, half of whom had PTSD, completed the Clinician-Administered PTSD Scale, Anxiety Sensitivity Inventory, and a fear conditioning and extinction paradigm during the midluteal (mLP) and early-follicular (eFP) menstrual cycle phases. RESULTS: In the mLP, stronger SCR to stimuli paired with shock (CS +) during fear acquisition significantly predicted greater PTSD symptoms only when AS was high and after removing an outlier. This appeared driven by effects on Numbing and Hyperarousal symptom clusters. Other hypothesized interactions between AS and CS responses were not significant. However, in the eFP, differential SCR between the CS + and CS- during extinction predicted significantly greater PTSD symptoms, and there was a trend for this effect being stronger as AS increased. CONCLUSIONS: Results offer preliminary evidence that high AS contributes to a stronger relationship between SCR during fear acquisition and PTSD symptoms, at least among women in the mLP. Further research investigating the impact of individual differences in traits such as AS on the relationship between conditioned fear responses and PTSD symptoms is warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pleiotropic endophenotypic and phenotype effects of GABAergic neurosteroid synthesis deficiency in posttraumatic stress disorder.

PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at GABAA receptors. These neurosteroids modulate neuronal firing rate, regional brain connectivity, and activation of amygdala-mediated autonomic nervous system, hypothalamic-pituitary-adrenal axis, and behavioral reactions to unconditioned and conditioned threat. They also play critical roles in learning and memory processes such as extinction and extinction retention and inhibit toll-like receptor activation of intracellular pro-inflammatory pathways. Deficient synthesis of these neurosteroids thus may contribute to individually variable PTSD clinical phenotypes encompassing symptom severity, capacity for PTSD recovery, and vulnerability to common PTSD-comorbidities such as major depression, chronic pain, alcohol and nicotine dependence, cardiovascular disease, metabolic syndrome, reproductive disorders, and autoimmune conditions.

A role for deficits in GABAergic neurosteroids and their metabolites with NMDA receptor antagonist activity in the pathophysiology of posttraumatic stress disorder.

Trauma-focused psychotherapies show general efficacy in post-traumatic stress disorder (PTSD), although outcomes vary substantially among individuals with PTSD and many patients do not achieve clinically meaningful symptom improvement. Several factors may contribute to poor treatment response, including genetic or environmental (e.g., stress) effects on neurobiological factors involved in learning and memory processes critical to PTSD recovery. In this review, we discuss the relationship between deficient GABAergic neurosteroid metabolites of progesterone, allopregnanolone (Allo) and pregnanolone (PA), and PTSD symptoms in men and women or PTSD-like behavioral abnormalities observed in male rodent models of PTSD. We also review the role and molecular underpinnings of learning and memory processes relevant to PTSD recovery, including extinction, extinction retention, reconsolidation of reactivated aversive memories and episodic non-aversive memory. We then discuss preclinical and clinical research that supports a role in these learning and memory processes for GABAergic neurosteroids and sulfated metabolites of Allo and PA that allosterically antagonize NMDA receptor function. Studies supporting the possible therapeutic impact of appropriately timed, acutely administered Allo or Allo analogs to facilitate extinction retention and/or block reconsolidation of aversive memories are also reviewed. Finally, we discuss important future directions for research in this area. Examining the varied and composite effects in PTSD of these metabolites of progesterone, as well as neuroactive derivatives of other parent steroids produced in the brain and the periphery, will likely enable a broadening of targets for treatment development. Defining contributions of these neuroactive steroids to common PTSD-comorbid psychiatric and medical conditions, as well as subpopulation-specific underlying dysfunctional physiological processes such as hypothalamic-pituitary-adrenal axis and immune system dysregulation, may also enable development of more effective multisystem precision medicines to prevent and treat the broader, polymorbid sequelae of extreme and chronic stress.

Suppression and acceptance in unipolar depression: Short-term and long-term effects on emotional responding.

OBJECTIVES: Transdiagnostic treatments increasingly include emotion regulation training focused on use of emotional suppression and acceptance. Despite the frequent use of these treatments in depression, little is known about the effects of these strategies in this population. DESIGN: An experimental study. METHODS: Eighty Veterans with unipolar depression participated in a study examining effects of these strategies on emotional responding (subjective, behavioural, and physiological). Physiological measures included: heart rate (HR), respiration (Resp), skin conductance (SC), and corrugator electromyography. On Day 1, participants were randomised to one of three conditions (acceptance, suppression, or control) and underwent an autobiographical sad mood induction. On Day 2, participants underwent a similar mood induction one week later. RESULTS: The suppression group demonstrated reduced physiological reactivity (Resp and SC) on Day 1. However, the suppression group reported decreased positive affect on Day 2. CONCLUSIONS: Results support short-term effectiveness and longer term costs from suppression use among depressed individuals. Findings may inform application of transdiagnostic emotion regulation treatments and suggest suppression functions differently in depressed versus other clinical populations.

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.

RATIONALE: Arginine vasopressin (AVP) is a neuropeptide that modulates both physiological and emotional responses to threat. Until recently, drugs that target vasopressin receptors (V1a) in the human central nervous system were unavailable. The development of a novel V1a receptor antagonist, SRX246, permits the experimental validation of vasopressin's role in the regulation of anxiety and fear in humans. OBJECTIVES: Here, we examined the effects of SRX246 in a proof-of-concept translational paradigm of fear (phasic response to imminent threat) and anxiety (prolonged response to potential threat). METHODS: Healthy volunteers received both SRX246 and placebo in a randomized, double-blind, counter-balanced order separated by a 5-7-day wash-out period. Threat consisted of unpleasant electric shocks. The "NPU" threat test probed startle reactivity during predictable threat (i.e., fear-potentiated startle) and unpredictable threat (i.e., anxiety-potentiated startle). RESULTS: As predicted, SRX246 decreased anxiety-potentiated startle independent of fear-potentiated startle. CONCLUSIONS: As anxiety-potentiated startle is elevated in anxiety and trauma-associated disorders and decreased by traditional anxiolytics such as SSRIs and benzodiazepines, the V1a receptor is a promising novel treatment target.

Associations between insomnia and reward learning in clinical depression.

BACKGROUND: Depression and insomnia commonly co-occur. Yet, little is known about the mechanisms through which insomnia influences depression. Recent research and theory highlight reward system dysfunction as a potential mediator of the relationship between insomnia and depression. This study is the first to examine the impact of insomnia on reward learning, a key component of reward system functioning, in clinical depression. METHODS: The sample consisted of 72 veterans with unipolar depression who endorsed sleep disturbance symptoms. Participants completed the Structured Clinical Interview for DSM-IV, self-report measures of insomnia, depression, and reward processing, and a previously validated signal detection task (Pizzagalli et al., 2005, Biological Psychiatry, 57(4), 319-327). Trial-by-trial response bias (RB) estimates calculated for each of the 200 task trials were examined using linear mixed-model analyses to investigate change in reward learning. RESULTS: Findings demonstrated diminished rate and magnitude of reward learning in the Insomnia group relative to the Hypersomnia/Mixed Symptom group across the task. Within the Insomnia group, participants with more severe insomnia evidenced the lowest rates of reward learning, with increased RB across the task with decreasing insomnia severity. CONCLUSIONS: Among individuals with depression, insomnia is associated with decreased ability to learn associations between neutral stimuli and rewarding outcomes and/or modify behavior in response to differential receipt of reward. This attenuated reward learning may contribute to clinically meaningful decreases in motivation and increased withdrawal in this comorbid group. Results extend existing theory by highlighting impairments in reward learning specifically as a potential mediator of the association between insomnia and depression.

Plasma gamma-aminobutyric acid (GABA) levels and posttraumatic stress disorder symptoms in trauma-exposed women: a preliminary report.

RATIONALE: Aberrations in the stress response are associated with posttraumatic stress disorder (PTSD) symptom development, maintenance, and severity. Gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, may play a key role in stress recovery. OBJECTIVES: In this preliminary study, we examined whether plasma GABA levels differed between women with PTSD and trauma-exposed healthy controls. METHODS: Thirty participants provided plasma samples during two phases of the menstrual cycle: the early follicular phase and the mid-luteal phase. During each phase, blood was drawn after 45 min of rest, and after mild and moderately stressful psychophysiological tasks. Plasma GABA levels were measured using HPLC-mass spectrometry (LC-MS/MS). RESULTS: In analyses using PTSD diagnosis as a categorical group variable, women with and without a diagnosis of PTSD did not differ in plasma GABA levels (ps > .18). However, in analyses examining PTSD symptom severity as a continuous variable, there was a trend-level positive association between more severe PTSD symptoms and higher plasma GABA levels across the four blood draws (p = .06). In analyses examining DSM-IV PTSD symptom clusters separately, dysphoria symptoms were positively and significantly associated with plasma GABA levels (p = .03). Similarly, there was a trend-level positive association between avoidance cluster symptoms and plasma GABA levels (p = .06). Plasma GABA levels were not modulated by experimentally induced stress or menstrual cycle phase. CONCLUSIONS: Dysregulation in GABA may be a neurobiological marker and/or potential treatment target for women with PTSD symptom profiles characterized by prominent dysphoria and avoidance cluster symptoms.

The Impact of the Menstrual Cycle and Underlying Hormones in Anxiety and PTSD: What Do We Know and Where Do We Go From Here?

PURPOSE OF REVIEW: This paper reviews the recent literature on menstrual cycle phase effects on outcomes relevant to anxiety and PTSD, discusses potential neurobiological mechanisms underlying these effects, and highlights methodological limitations impeding scientific advancement. RECENT FINDINGS: The menstrual cycle and its underlying hormones impact symptom expression among women with anxiety and PTSD, as well as psychophysiological and biological processes relevant to anxiety and PTSD. The most consistent findings are retrospective self-report of premenstrual exacerbation of anxiety symptoms and the protective effect of estradiol on recall of extinction learning among healthy women. Lack of rigorous methodology for assessing menstrual cycle phase and inconsistent menstrual cycle phase definitions likely contribute to other conflicting results. Further investigations that address these limitations and integrate complex interactions between menstrual cycle phase-related hormones, genetics, and psychological vulnerabilities are needed to inform personalized prevention and intervention efforts for women.

Associations between PTSD-Related extinction retention deficits in women and plasma steroids that modulate brain GABAA and NMDA receptor activity.

Several studies have demonstrated poor retention of extinction learning among individuals with posttraumatic stress disorder (PTSD). Gonadal hormone signaling in brain appears to influence the retention of extinction learning differently in women with and without PTSD. Women with PTSD, compared to trauma-exposed women without PTSD, show relative deficits in extinction retention during the mid-luteal phase (mLP) of the menstrual cycle, compared to the early follicular phase (eFP). A PTSD-related reduction in conversion of progesterone to its GABAergic metabolites allopregnanolone (Allo) and pregnanolone (PA) may contribute to these findings. The current study in trauma-exposed women with (n = 9) and without (n = 9) PTSD investigated associations between extinction retention and plasma Allo + PA levels, as well as the ratio of Allo + PA to 5α-dihydroprogesterone (5α-DHP), the immediate steroid precursor for Allo. The study also investigated the relationship between extinction retention and the ratio of Allo + PA to dehydroepiandrosterone (DHEA), an adrenally-derived GABAA receptor antagonist. Study participants completed differential fear-conditioning during both the eFP and mLP of the menstrual cycle. Analyses revealed a strong positive relationship between resting plasma Allo + PA levels and extinction retention during the mLP in the women with, but not without, PTSD (e.g., diagnosis X Allo + PA interaction controlling for early extinction: ß = -.0008, p = .003). A similar pattern emerged for the Allo + PA to 5α-DHP ratio (ß = -.165, p = .071), consistent with a PTSD-related block in production of Allo and PA at the enzyme 3α-hydroxysteroid dehydrogenase. The ratio of Allo + PA to DHEA appeared to influence extinction retention only during the eFP when Allo + PA and DHEA levels are comparable and thus may compete for effects on GABAA receptor function. This study aligns with male rodent PTSD models linking experimental reductions in brain Allo levels to deficits in extinction retention and suggests that targeting PTSD-related deficits in GABAergic neurosteroid synthesis may be therapeutic.

Examination of the stability of the anxiety sensitivity index across the menstrual cycle in trauma-exposed women with and without PTSD.

Background and Objectives: Anxiety sensitivity (AS), as measured by the Anxiety Sensitivity Index (ASI), has consistently been studied as a trait-level predictor of a variety of emotional and physical health conditions, including premenstrual symptoms. The menstrual cycle influences symptom expression and stress reactivity among anxiety and stress-related disorders. However, research has yet to directly evaluate the stability of AS across the various phases of the menstrual cycle, particularly in clinical populations with high levels of AS and with documented menstrual cycle differences in symptoms such as women with posttraumatic stress disorder (PTSD).Design and Methods: The current study examined whether AS fluctuates as a function of menstrual cycle phase among a community sample of trauma-exposed women (N = 48) with and without PTSD. Participants completed the ASI, including subscales assessing sensitivity to physical, cognitive, and social symptoms of anxiety, during early follicular and mid-luteal menstrual cycle phases.Results: Results revealed that ASI scores remained relatively stable across the different phases of the menstrual cycle assessed; evidence for stability was particularly strong for the subscale assessing sensitivity to physical symptoms of anxiety.Conclusion: This study provides additional support for the conceptualization of AS as a stable, trait-like, cognitive risk factor.

Associations Between Trauma-Related Rumination and Symptoms of Posttraumatic Stress and Depression in Treatment-Seeking Female Veterans.

Trauma-related rumination is a cognitive style characterized by repetitive negative thinking about the causes, consequences, and implications of a traumatic experience. Frequent trauma-related rumination has been linked to posttraumatic stress disorder (PTSD) and depression in civilian samples but has yet to be examined among military veterans. This study extended previous research by examining trauma-related rumination in female veterans who presented to a Veterans Affairs women's trauma recovery clinic (N = 91). The study had two main aims: (a) to examine associations between trauma-related rumination and specific PTSD symptoms, adjusting for the overlap between trauma-related rumination and other relevant cognitive factors, such as intrusive trauma memories and self-blame cognitions; and (b) to assess associations between trauma-related rumination, PTSD, and depression, adjusting for symptom comorbidity. At intake, patients completed a semistructured interview and self-report questionnaires. Primary diagnoses were confirmed via medical record review. Trauma-related rumination was common, with more than 80% of patients reporting at least sometimes engaging in this cognitive style in the past week. After adjusting for other relevant cognitive factors, trauma-related rumination was significantly associated with several specific PTSD symptoms, rp s = .33-.48. Additionally, the severity of trauma-related rumination was associated with overall PTSD symptom severity, even after adjusting for comorbid depression symptoms, rp 2 = .35. In contrast, the association between trauma-related rumination and depressive symptom severity was not significant after adjusting for comorbid PTSD symptoms, rp 2 = .008. These results highlight trauma-related rumination as a unique contributing factor to the complex clinical presentation for a subset of trauma-exposed veterans.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Asociaciones entre la rumiación relacionada con el trauma y síntomas de estrés postraumático y depresión en Mujeres Veteranas en busca de tratamiento RUMINACIÓN RELACIONADA CON EL TRAUMA EN MUJERES VETERANAS La rumiación relacionada con el trauma es un estilo cognitivo caracterizado por pensamientos negativos repetitivos sobre las causas, consecuencias e implicaciones de una experiencia traumática. Frecuentemente la rumiación relacionada con el trauma se ha relacionado con el trastorno de estrés postraumático (TEPT) y la depresión en muestras de civiles, pero aún no se ha examinado entre los veteranos militares. Este estudio extendió la investigación previa al examinar la rumiación relacionada con el trauma en mujeres veteranas que acudieron a una clínica de recuperación de trauma para mujeres del VA (N = 91). El estudio tenía dos objetivos principales: examinar (a) las asociaciones entre la rumiación relacionada con el trauma y los síntomas específicos de TEPT, ajustándose a la superposición entre la rumiación relacionada con el trauma y otros factores cognitivos relevantes, como los recuerdos intrusivos del trauma y las cogniciones de auto-culpa; y (b) asociaciones entre rumiación relacionada con el trauma, TEPT y depresión, ajustando la comorbilidad de los síntomas. En el momento del ingreso, los pacientes completaron una entrevista semiestructurada y cuestionarios de autoinforme. Los diagnósticos primarios fueron confirmados a través de la revisión de la historia clínica. La rumiación relacionada con el trauma fue común, con más del 80% de los pacientes que informaron que al menos a veces se involucraron en este estilo cognitivo en la última semana. Después de ajustar otros factores cognitivos relevantes, la rumiación relacionada con el trauma se asoció significativamente con varios síntomas específicos de TEPT, rp s = .33 - .48. Además, la gravedad de la rumiación relacionada con el trauma se asoció con la gravedad general de los síntomas del TEPT incluso después de ajustar los síntomas de depresión comórbida, rp 2 = .35. En contraste, la asociación entre la rumiación relacionada con el trauma y la gravedad de los síntomas depresivos no fue significativa después de ajustar los síntomas de trastorno de estrés postraumático comórbido, rp 2 = .008. Estos resultados resaltan la rumiación relacionada con el trauma como un factor único contribuyente a la compleja presentación clínica para un subconjunto de veteranas expuestas a traumas.

Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD.

Allopregnanolone and pregnanolone (together termed allo + pregnan) are neurosteroid metabolites of progesterone that equipotently facilitate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. The adrenal steroid dehydroepiandrosterone (DHEA) allosterically antagonizes GABAA receptors and facilitates N-methyl-D-aspartate (NMDA) receptor function. In prior research, premenopausal women with posttraumatic stress disorder (PTSD) displayed low cerebrospinal fluid (CSF) levels of allo + pregnan [undifferentiated by the gas chromatography-mass spectrometry (GC-MS) method used] that correlated strongly and negatively with PTSD reexperiencing and negative mood symptoms. A PTSD-related decrease in the ratio of allo + pregnan to 5α-dihydroprogesterone (5α-DHP: immediate precursor for allopregnanolone) suggested a block in synthesis of these neurosteroids at 3α-hydroxysteroid dehydrogenase (3α-HSD). In the current study, CSF was collected from unmedicated, tobacco-free men with PTSD (n = 13) and trauma-exposed healthy controls (n = 17) after an overnight fast. Individual CSF steroids were quantified separately by GC-MS. In the men with PTSD, allo + pregnan correlated negatively with Clinician-Administered PTSD Scale (CAPS-IV) total (ρ=-0.74, p = 0.006) and CAPS-IV derived Simms dysphoria cluster (ρ=-0.71, p = 0.01) scores. The allo+pregnan to DHEA ratio also was negatively correlated with total CAPS (ρ=-0.74, p = 0.006) and dysphoria cluster (ρ=-0.79, p = 0.002) scores. A PTSD-related decrease in the 5α-DHP to progesterone ratio indicated a block in allopregnanolone synthesis at 5α-reductase. This study suggests that CSF allo + pregnan levels correlate negatively with PTSD and negative mood symptoms in both men and women, but that the enzyme blocks in synthesis of these neurosteroids may be sex-specific. Consideration of sex, PTSD severity, and function of 5α-reductase and 3α-HSD thus may enable better targeting of neurosteroid-based PTSD treatments.

Contingency management and cognitive behavioral therapy for trauma-exposed smokers with and without posttraumatic stress disorder.

INTRODUCTION: Trauma-exposed individuals with and without posttraumatic stress disorder (PTSD) are more likely to smoke and less successful in quit attempts than individuals without psychopathology. Contingency management (CM) techniques (i.e., incentives for abstinence) have demonstrable efficacy for smoking cessation in some populations with psychopathology, but have not been well tested in PTSD. This pilot study examined the feasibility of CM plus brief cognitive behavioral therapy (CBT) in promoting smoking cessation among trauma-exposed individuals with and without PTSD. METHODS: Fifty trauma-exposed smokers (18 with PTSD) were asked to abstain from tobacco and nicotine replacement therapy for one month. During week one of cessation, CBT was provided daily and increasing CM stipends were paid for each continuous day of biochemically-verified abstinence; CM stipends were withheld in response to smoking lapses and reset to the initial payment level upon abstinence resumption. CBT and fixed payments for study visits were provided during the subsequent three weeks. RESULTS: Of the 50 eligible participants who attended at least one pre-quit visit (49% female, 35% current PTSD), 43 (86%) attended the first post-quit study visit, 32 (64%) completed the first week of CM/CBT treatment, and 26 (52%) completed the study. Post-quit seven-day point prevalence abstinence rates for participants with and without PTSD, respectively, were similar: 39% vs. 38% (1 week), 33% vs. 28% (2 weeks), 22% vs. 19% (3 weeks), and 22% vs. 13% (4 weeks). CONCLUSIONS: Use of CM + CBT to support tobacco abstinence is a promising intervention for trauma-exposed smokers with and without PTSD.

Neurotransmitter, Peptide, and Steroid Hormone Abnormalities in PTSD: Biological Endophenotypes Relevant to Treatment.

PURPOSE OF REVIEW: This review summarizes neurotransmitter, peptide, and other neurohormone abnormalities associated with posttraumatic stress disorder (PTSD) and relevant to development of precision medicine therapeutics for PTSD. RECENT FINDINGS: As the number of molecular abnormalities associated with PTSD across a variety of subpopulations continues to grow, it becomes clear that no single abnormality characterizes all individuals with PTSD. Instead, individually variable points of molecular dysfunction occur within several different stress-responsive systems that interact to produce the clinical PTSD phenotype. Future work should focus on critical interactions among the systems that influence PTSD risk, severity, chronicity, comorbidity, and response to treatment. Effort also should be directed toward development of clinical procedures by which points of molecular dysfunction within these systems can be identified in individual patients. Some molecular abnormalities are more common than others and may serve as subpopulation biological endophenotypes for targeting of currently available and novel treatments.

Heart rate reactivity to trauma-related imagery as a measure of PTSD symptom severity: Examining a new cohort of Veterans.

For over three decades, there has been considerable research documenting increased physiological reactivity to trauma-related stimuli as a characteristic feature of posttraumatic stress disorder (PTSD). The present study explored the potential for physiological assessment to aid in defining and validating screening criteria for the presence of significant PTSD-related symptoms in a sample of OEF/OIF/OND Veterans seeking care in a VA post-deployment health clinic. Heart rate reactivity scores during the imagining phase of the script-driven imagery paradigm were compared across groups of individuals with and without probable PTSD diagnoses, as defined by PCL-IV cutoff scores ranging from 40 to 60. Significant differences were found for groups defined by PCL-IV cutoff scores of 50 and 60, with 50 producing the largest effect size. Diagnosing PTSD is made challenging by the presence of overlapping symptoms shared with other diagnoses, as well as by the necessity for patients to accurately report their symptoms. An objective physiological measure capable of accurately differentiating individuals with and without PTSD provides potential adjunctive diagnostic and treatment information to clinicians. The present findings support the validity of physiological reactivity during SDI as a NIMH RDoC measure that can be used in research and clinical applications assessing trauma-related symptom severity.