Yael I. Nillni

Extinction retention and the menstrual cycle: Different associations for women with posttraumatic stress disorder.

The propensity to acquire and retain conditioned fear responses may contribute to the risk of developing and maintaining posttraumatic stress disorder (PTSD) following a traumatic event. There is growing evidence that the gonadal hormones estrogen and progesterone are associated with how well women retain extinction of previously conditioned fear responses. Thus, sex steroid effects may contribute to the increased prevalence of PTSD in women. For the current study, 32 nonmedicated female trauma survivors with and without PTSD completed a differential fear conditioning task both during the early follicular phase of the menstrual cycle when estradiol and progesterone levels are low, and during the midluteal phase when estradiol and progesterone levels are high. Skin conductance served as the measure of conditioned fear. Women with PTSD, compared to those without, showed impaired retention of extinction learning in the midluteal phase of the menstrual cycle. Therefore, the impact of menstrual phase on extinction retention may differ between women with and without PTSD. These findings raise potential considerations regarding the coordination of psychopharmacologic and trauma exposure-based treatments for PTSD with specific phases of the menstrual cycle.

Menstrual Cycle Effects on Psychological Symptoms in Women With PTSD

The menstrual cycle has been implicated as a sex-specific biological process influencing psychological symptoms across a variety of disorders. Limited research exists regarding the role of the menstrual cycle in psychological symptoms among women with posttraumatic stress disorder (PTSD). The current study examined the severity of a broad range of psychological symptoms in both the early follicular (Days 2-6) and midluteal (6-10 days postlutenizing hormone surge) phases of the menstrual cycle in a sample of trauma-exposed women with and without PTSD (N = 49). In the sample overall, total psychological symptoms (d = 0.63), as well as depression (d = 0.81) and phobic anxiety (d = 0.81) symptoms, specifically, were increased in the early follicular compared to midluteal phase. The impact of menstrual cycle phase on phobic anxiety was modified by a significant PTSD × Menstrual Phase interaction (d = 0.63). Women with PTSD reported more severe phobic anxiety during the early follicular versus midluteal phase, whereas phobic anxiety did not differ across the menstrual cycle in women without PTSD. Thus, the menstrual cycle appears to impact fear-related symptoms in women with PTSD. The clinical implications of the findings and future research directions are discussed.

Neuroactive steroids and PTSD treatment

This review highlights early efforts to translate pre-clinical and clinical findings regarding the role of neuroactive steroids in stress adaptation and PTSD into new therapeutics for PTSD. Numerous studies have demonstrated PTSD-related alterations in resting levels or the reactivity of neuroactive steroids and their targets. These studies also have demonstrated substantial variability in the dysfunction of specific neuroactive steroid systems among PTSD subpopulations. These variabilities have been related to the developmental timing of trauma, severity and type of trauma, genetic background, sex, reproductive state, lifestyle influences such as substance use and exercise, and the presence of comorbid conditions such as depression and chronic pain. Nevertheless, large naturalistic studies and a small placebo-controlled interventional study have revealed generally positive effects of glucocorticoid administration in preventing PTSD after trauma, possibly mediated by glucocorticoid receptor-mediated effects on other targets that impact PTSD risk, including other neuroactive steroid systems. In addition, clinical and preclinical studies show that administration of glucocorticoids, 17β-estradiol, and GABAergic neuroactive steroids or agents that enhance their synthesis can facilitate extinction and extinction retention, depending on dose and timing of dose in relation to these complex PTSD-relevant recovery processes. This suggests that clinical trials designed to test neuroactive steroid therapeutics in PTSD may benefit from such considerations; typical continuous dosing regimens may not be optimal. In addition, validated and clinically accessible methods for identifying specific neuroactive steroid system abnormalities at the individual level are needed to optimize both clinical trial design and precision medicine based treatment targeting.

Unique and related predictors of major depressive disorder, posttraumatic stress disorder, and their comorbidity after Hurricane Katrina.

Abstract The current study examined demographic and psychosocial factors that predict major depressive disorder (MDD) and comorbid MDD/posttraumatic stress disorder (MDD/PTSD) diagnostic status after Hurricane Katrina, one of the deadliest and costliest hurricanes in the history of the United States. This study expanded on the findings published in the article by Galea, Tracy, Norris, and Coffey (J Trauma Stress 21:357–368, 2008), which examined the same predictors for PTSD, to better understand related and unique predictors of MDD, PTSD, and MDD/PTSD comorbidity. A total of 810 individuals representative of adult residents living in the 23 southernmost counties of Mississippi before Hurricane Katrina were interviewed. Ongoing hurricane-related stressors, low social support, and hurricane-related financial loss were common predictors of MDD, PTSD, and MDD/PTSD, whereas educational and marital status emerged as unique predictors of MDD. Implications for postdisaster relief efforts that address the risk for both MDD and PTSD are discussed.

Deployment stressors and physical health among OEF/OIF veterans: the role of PTSD.

OBJECTIVE There is a large body of literature documenting the relationship between traumatic stress and deleterious physical health outcomes. Although posttraumatic stress disorder (PTSD) symptoms have been proposed to explain this relationship, previous research has produced inconsistent results when moderating variables such as gender or type of traumatic stressor are considered. Within a large sample of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, the current study examined if deployment stressors (i.e., combat stress, harassment stress) contributed unique variance to the prediction of physical health symptoms (i.e., pain, nonpain) beyond the effects of PTSD symptoms. METHODS A total of 2,332 OEF/OIF Veterans, with equal representation of women and men, completed a series of self-report measures assessing deployment stressors, PTSD symptoms, and physical health symptoms. RESULTS RESULTS revealed that harassment, but not combat stress, added unique variance in the prediction of pain and nonpain symptoms after accounting for PTSD symptoms. CONCLUSIONS This study extends the existing literature by demonstrating the unique influence of harassment stress on physical health outcomes. Specifically, the relationship between combat stress and physical health symptoms appears to be explained mainly by an individuals experience of PTSD symptoms, whereas the relationship between harassment stress and physical health symptoms is not fully explained by PTSD symptoms, suggesting that other variables may be involved in the pathway from harassment stress to physical health symptoms.

Prepulse inhibition deficits in women with PTSD

Prepulse inhibition (PPI) is an automatic and preattentive process, whereby a weak stimulus attenuates responding to a sudden and intense startle stimulus. PPI is a measure of sensorimotor filtering, which is conceptualized as a mechanism that facilitates processing of an initial stimulus and is protective from interruption by a later response. Impaired PPI has been found in (a) healthy women during the luteal phase of the menstrual cycle, and (b) individuals with types of psychopathology characterized by difficulty suppressing and filtering sensory, motor, or cognitive information. In the current study, 47 trauma-exposed women with or without posttraumatic stress disorder (PTSD) completed a PPI session during two different phases of the menstrual cycle: the early follicular phase, when estradiol and progesterone are both low, and the midluteal phase, when estradiol and progesterone are both high. Startle stimuli were 100 dB white noise bursts presented for 50 ms, and prepulses were 70 dB white noise bursts presented for 20 ms that preceded the startle stimuli by 120 ms. Women with PTSD showed deficits in PPI relative to the healthy trauma-exposed participants. Menstrual phase had no effect on PPI. These results provide empirical support for individuals with PTSD having difficulty with sensorimotor filtering. The potential utility of PPI as a Research Domain Criteria (RDoC) phenotype is discussed.

Depression, anxiety, and psychotropic medication use and fecundability:

BACKGROUND The literature regarding the associations between depression, anxiety, and fecundity is inconsistent. While cross-sectional studies suggest that depression and/or anxiety may adversely affect fecundity, the sole cohort study showed only a small association. OBJECTIVE We sought to evaluate the association of self-reported depressive symptoms, self-reported diagnoses of depression and anxiety, and psychotropic medication use with fecundability in a prospective cohort study. STUDY DESIGN Data were derived from Pregnancy Study Online (PRESTO), an Internet-based preconception cohort study of couples attempting to conceive in the United States and Canada. At baseline, female participants completed a survey that assessed demographic information, history of physician-diagnosed depression and anxiety, self-reported depressive symptoms (assessed by the Major Depression Inventory), and use of psychotropic medications. Women completed follow-up surveys every 8 weeks for up to 12 months or until reported conception to assess changes in exposures and pregnancy status. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities regression models. The analysis was restricted to 2146 women who had been attempting to conceive for ≤6 cycles at study entry. RESULTS Severe depressive symptoms at baseline, regardless of treatment, were associated with decreased fecundability compared with no or low depressive symptoms (fecundability ratio, 0.62; 95% confidence interval, 0.43-0.91). The fecundability ratio associated with a 10-unit increase in Major Depression Inventory score was 0.90 (95% confidence interval, 0.83-0.97). Women who reported moderate to severe depressive symptoms and had never received psychotropic medications (fecundability ratio, 0.69; 95% confidence interval, 0.48-0.99) or who were currently being treated with psychotropic medications (fecundability ratio, 0.72; 95% confidence interval, 0.44-1.20) had decreased fecundability relative to women who had no/mild depressive symptoms and had never used psychotropic medications. Former users of psychotropic medications had increased fecundability regardless of the presence of no/mild depressive symptoms (fecundability ratio, 1.22; 95% confidence interval, 1.06-1.39) or moderate to severe depressive symptoms (fecundability ratio, 1.18; 95% confidence interval, 0.80-1.76). CONCLUSION We found an inverse association between depressive symptoms and fecundability, independent of psychotropic medication use. Use of psychotropic medications did not appear to harm fecundability.

Cognitive vulnerability in moderate, mild, and low seasonality.

Abstract This study examined the association between cognitive vulnerability factors and seasonality. Students (N = 88), classified based on the Seasonal Pattern Assessment Questionnaire as experiencing moderate (n = 26) or mild (n = 32) seasonality, and nondepressed, low-seasonality controls (n = 30) completed explicit (i.e., dysfunctional attitudes, automatic negative thoughts, seasonal attitudes, and rumination) and implicit (i.e., implicit associations test) measures of cognitive vulnerability at one winter and one nonwinter assessment. Relative to low- and mild-seasonality participants, moderate-seasonality participants endorsed more automatic thoughts and rumination in winter and more dysfunctional attitudes across both seasons. Moderate- and mild-seasonality participants endorsed more maladaptive seasonal attitudes than did low-seasonality participants. All groups demonstrated increased dysfunctional attitudes, automatic thoughts, and rumination and stronger implicit associations about light and dark during the winter. The findings support a possible cognitive mechanism of winter depression onset and/or maintenance unique to individuals with moderate, as opposed to mild, seasonality.

Longitudinal course of anxiety sensitivity and PTSD symptoms in cognitive-behavioral therapies for PTSD.

Anxiety sensitivity (AS) has been conceptualized as trait-like vulnerability and maintenance factor for PTSD. Although recent literature has demonstrated its malleability during treatment, few have examined its influence on and effect from PTSD treatment. Using multilevel regression analyses we examined: (a) changes in AS during treatment and (b) whether pre-treatment AS predicted PTSD treatment response, in sample of female victims of interpersonal trauma receiving one of three treatments (cognitive processing therapy, cognitive processing therapy-cognitive, and written accounts). Participants exhibited reductions in total ASI scores from pre- to post-treatment. Growth curve modeling revealed slightly different trajectories of PTSD symptoms as a function of pre-treatment AS, and overall decreases in PTSD symptoms during treatment were not associated with pretreatment AS. Pretreatment AS dimensions impacted PTSD total scores and symptoms clusters differentially. Clinical and theoretical implications for these results are discussed.

Cognitive Change Across Cognitive-Behavioral and Light Therapy Treatments for Seasonal Affective Disorder: What Accounts for Clinical Status the Next Winter?

Efficacious treatments for seasonal affective disorder include light therapy and a seasonal affective disorder-tailored form of cognitive-behavioral therapy. Using data from a parent clinical trial, these secondary analyses examined the relationship between cognitive change over treatment with cognitive-behavioral therapy, light therapy, or combination treatment and mood outcomes the next winter. Sixty-nine participants were randomly assigned to 6-weeks of cognitive-behavioral therapy, light therapy, or combination treatment. Cognitive constructs (i.e., dysfunctional attitudes, negative automatic thoughts, and rumination) were assessed at pre- and post-treatment. Dysfunctional attitudes, negative automatic thoughts, and rumination improved over acute treatment, regardless of modality; however, in participants randomized to solo cognitive-behavioral therapy, a greater degree of improvement in dysfunctional attitudes and automatic thoughts was uniquely associated with less severe depressive symptoms the next winter. Change in maladaptive thoughts during acute treatment appears mechanistic of solo cognitive-behavioral therapy’s enduring effects the next winter, but is simply a consequence of diminished depression in light therapy and combination treatment.