Tory Eisenlohr-Moul, Ph.D. | University of Illinois at Chicago, College of Medicine (original) (raw)

Papers by Tory Eisenlohr-Moul, Ph.D.

BMC Psychiatry , 2022

Background: Suicide is the second leading cause of death among Americans ages 10 to 34, with alar... more Background: Suicide is the second leading cause of death among Americans ages 10 to 34, with alarming recent increases in suicide rates among those assigned female at birth. A large body of evidence points to menstrual cycle influences on self-injurious thoughts and behaviors (STBs), suggesting that neurobiological hormone sensitivities, such as in premenstrual dysphoric disorder (PMDD), may drive suicide risk in females. However, existing studies of STBs in PMDD use cross-sectional self-report measures of PMDD with poor validity. As a first step to establish accurate prevalence rates of STBs in PMDD, we examined the lifetime prevalence of STBs in a large global survey of patients reporting a diagnosis of PMDD based on daily ratings. Method: Individuals with self-reported PMDD symptoms were invited to an online survey through online support groups for PMDD and social media posts from PMDD awareness accounts. Participants reported demographics, whether they had been diagnosed with PMDD by a healthcare provider using daily ratings, STBs using the Columbia Suicide Severity Rating Scale, and history of lifetime comorbid psychiatric diagnoses. Results: Of 2,689 survey completers, 599 (23%) reported a diagnosis with PMDD based on two months of daily ratings and were included in analyses. We observed high rates of lifetime active suicidal ideation (72%), planning (49%), intent (42%), preparing for an attempt (40%), and attempt (34%), as well as non-suicidal self-injury (51%). The majority (70%) of the sample reported at least one lifetime comorbid psychiatric diagnosis. Predictors of lifetime active suicidal ideation included nulliparity, low-to-moderate (vs. high) income, and history of diagnosis with major depression or post-traumatic stress disorder. Predictors of lifetime attempts among those reporting lifetime active ideation included older age, nulliparity, lower income, and history of diagnosis with post-traumatic stress disorder or borderline personality disorder. Conclusions: These data indicate high rates of STBs among those reporting prospective diagnosis of PMDD and highlight the need for prospective research on mechanisms and prevention of STBs in PMDD. Clinical practice

The Clinical psychologist, 2019

Virtual reality (VR) models allow investigators to explore high-risk situations carefully in the ... more Virtual reality (VR) models allow investigators to explore high-risk situations carefully in the laboratory using physiological assess-ment strategies and controlled conditions not available in field settings. This article introduces the use of a virtual experience to examine the influence of self-regulatory skills training on female participants ’ reactions to a high-risk encounter with an aggressive male. Sixty-three female participants were recruited for the study. Demographic data indicated that 54 % of the participants were not currently in a relationship, 36.5 % were in a committed relationship, and 9.5 % were occasionally dating. After obtaining informed consent, participants were assigned randomly to either a diaphragmatic breathing training condition or an attention con-trol condition. Results indicated that both groups rated the virtual environment as equally realistic; the aggressive advances of the male were also perceived as equally real across the two experimental grou...

Archives of Women's Mental Health

Perinatal depression affects 6.5–12.9% of women, with high rates in women of color and comorbid p... more Perinatal depression affects 6.5–12.9% of women, with high rates in women of color and comorbid perinatal anxiety in up to 50% of cases. The Research Domain Criteria (RDoC) provides a translational framework for identifying transdiagnostic psychiatric symptoms, but its application in perinatal affective disorders (PNAD) is yet limited. Here, we identified RDoC-based transdiagnostic features of PNAD in 140 primarily low-income Black and Hispanic women at 272 total longitudinal visits across the perinatal period. Women completed RDoC self-report measures of potential threat and reward valuation—Behavioral Inhibition System/Behavioral Activation System scale (BIS/BAS) and Intolerance of Uncertainty Scale (IUS)—and measures of depression (Patient Health Questionnaire-9; PHQ-9) and anxiety (Generalized Anxiety Disorder-7; GAD-7). Longitudinal mixed effects models assessed associations of between-person (“trait-like”) and within-person (“state-like”) measures of potential threat (BIS/IUS) and reward valuation (BAS-Drive) with depression and anxiety symptoms. Higher “trait-like” BIS (standardized b = 2.33, p < .001) and IUS (b = 2.97, p < .001) scores, higher “state-like” BIS (b = .71, p < .001), and lower “state-like” BAS-Drive (b = − .58, p = .04) scores were associated with worse depressive symptoms. Higher “trait-like” BIS (b = 2.22, p < .001) and IUS (b = 2.73, p < .001) and higher “state-like” BIS scores (b = .92, p < .001) were associated with worse anxiety symptoms. Potential threat may be a prominent, transdiagnostic feature of perinatal anxiety and depression, whereas reward valuation may be a non-transdiagnostic, weaker feature of perinatal depression. Potential threat is important as both a “trait-like” feature that is sustained across the perinatal period and a “state-like” feature that varies within a woman across pregnancy. Grounded in RDoC, this work reveals neurobiological targets for translational research into PNAD.

Journal of Women's Health

Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that affects ∼5% of ... more Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that affects ∼5% of menstruating individuals. Although symptoms are limited to the luteal phase of the menstrual cycle, PMDD causes significant distress and impairment across a range of activities. PMDD is under-recognized by health care providers, can be difficult to diagnose, and lies at the intersection of gynecology and psychiatry. Thus, many patients are misdiagnosed, or encounter challenges in seeking care. The aim of this study was to examine patients' experiences with different health care specialties when seeking care for PMDD symptoms. Methods: We examined data from the 2018 Global Survey of Premenstrual Disorders conducted by the International Association for Premenstrual Disorders (IAPMD). Patients rated their health care providers (general practitioners, psychiatrists, gynecologists, psychotherapists) in three key areas related to treatment of premenstrual mood complaints: interpersonal factors, awareness and knowledge of PMDD, and whether the patient was asked to track symptoms daily. Intraclass correlations examined between- and within-person variance. Multilevel regression models predicted ratings on each provider competency item, with ratings nested within individuals to examine the within-patient effect of provider type on outcomes. Results: The sample included 2,512 patients who reported seeking care for PMDD symptoms. Regarding interpersonal factors, psychotherapists were generally rated the highest. On awareness and knowledge of PMDD, gynecologists and psychiatrists were generally rated the highest. Gynecologists were more likely than other providers to ask patients to track symptoms daily. Conclusions: These findings suggest that different providers have different strengths in assessing and treating PMDD. Further, graduate and medical training programs may benefit from increased curricular development regarding evidence-based evaluation and treatment of PMDD.

Psychoneuroendocrinology

Progesterone (P4) can be metabolized to two general classes of neuroactive steroids (NAS) -those ... more Progesterone (P4) can be metabolized to two general classes of neuroactive steroids (NAS) -those like allopregnanolone (ALLO) and pregnanolone (PA) which are positive allosteric modulators of the Gamma Aminobutyric Acid type A (GABAA) receptor and those like isoallopregnanolone (ISOALLO) and epipregnanolone (EPI) which are negative allosteric modulators of the GABAA receptor. While exogenous administration of ALLO is effective in treating postpartum depression, knowledge gaps remain in the dynamic interplay of NAS across the perinatal period. In particular little is known about ALLO and PA in relation to depression earlier in pregnancy, and the role of ISOALLO and EPI in relation to depression at any point in the perinatal period. In a prospective, nested case/control study in low-income women of color, we compared the metabolism of P4 to four NAS (i.e., ratios ALLO:P4, PA:P4, ISOALLO:P4, EPI:P4) in pregnant women with depression at either or both of the first and second trimesters (cases) and women without depression at either time point (controls). Fifty women (36% depressed, 56% Black, 28% Latina) completed depression screening using a computerized adaptive test of mental health (CAT-MH™) and provided blood serum samples in both trimesters. In longitudinal mixed effects models of both trimesters, PND cases showed higher ratios of ALLO:P4 (p = .002) and PA:P4 (p = .03) compared to controls. In regression models of only first trimester data, there was no significant difference in NAS ratios between cases and controls (p > .05). Conversely, in models of the second trimester, ratios of PA:P4 (p = .002) and ISOALLO:P4 (p = .01) were significantly higher in cases compared to controls, and ratios of ALLO:P4 (p = .08) and EPI:P4 (p = .1) also trended higher in cases. The most severe cases, those with depression at both trimesters, showed an increase in ALLO:P4 (p = .06) and EPI:P4 (p < .001) ratios from the first to the second trimester, whereas controls showed a decrease in these ratios. Secondary analyses confirmed higher levels of ALLO (p = .04) and PA (p = .07) overall in cases compared to controls, along with higher levels of PA (p = .005) and ISOALLO (p = .02) in the second trimester alone. This work suggests a dynamic relationship between NAS and PND; whereas low ALLO levels have been previously associated with postpartum depression, earlier in pregnancy a higher metabolism of P4 to ALLO (and higher ALLO levels) is associated with depression. Some women may show a hormone-sensitive depressive response to acute increases in NAS metabolism in early pregnancy.

Journal of Affective Disorders

Abstract Background : Accumulating evidence indicates that reduced activity within the monoamine ... more Abstract Background : Accumulating evidence indicates that reduced activity within the monoamine systems contributes to the pathophysiology of major depressive disorder (MDD) and suicide. In this study, we have tested the hypothesis that monoaminergic gene transcription is abnormally regulated in MDD and suicide. Methods : The transcription of specific monoaminergic genes was quantified by qPCR in the dorsolateral prefrontal cortex (DLPFC) of postmortem MDD subjects (n=80) and non-psychiatric controls (CTRL, n=32). Transcripts measured included monoaminergic transporters (the serotonin transporter (SERT), norepinephrine transporter (NET), dopamine transporter (DAT), plasma monoamine transporter (PMAT), vesicular monoamine transporter (VMAT)) and the tryptophan hydroxylase (TPH) enzymes, TPH1 and TPH2). We tested for transcriptional differences between diagnostic groups in addition to testing for differences specific to the depressed suicides. Results : Multivariate analysis of monoaminergic gene transcription revealed a sex by diagnosis interaction (F8,99=2.87, p=0.007). We report lower VMAT1 and PMAT expression in depressed males, and conversely higher VMAT2, TPH2 and NET expression in depressed females, relative to controls of the same sex (p Limitations : Gene expression measures were not associated with the presence of antidepressant medication. Nevertheless, to minimize the impact of medication status and other potential confounding variables, these were included as covariates in our analyses. Conclusions : We report sex differences in the transcription of monoaminergic genes in the DLPFC in MDD. Therefore abnormalities of monoaminergic gene expression may contribute to altered DLPFC activity exhibited in major depression.

Objectives: The goal of the current study was to refine and validate a revision of the Five Facet... more Objectives: The goal of the current study was to refine and validate a revision of the Five FacetMindfulness Questionnaire (FFMQ), with the goal of retaining its useful features and mitigatingthose features that have been identified to be problematic.Methods: A 30-item pilot version of the Balanced Inventory of Mindfulness-related Skills(BIMS) was developed by implementing the structured alternative item format (presenting bothpositive and negative aspects of each item) and revising the wording of items. Herein, wecollected data from a convenience sample of n=1,014 individuals, reduced to n=757 after datacleaning. We conducted exploratory factor analysis (EFA) and confirmatory factor analyses(CFA) on randomly separated subsets of the sample and explored response patterns andcorrelations with relevant measures (including a short-form of the FFMQ).Results: Parallel analysis and EFA indicated a five-factor, correlated structure across a final 27items (omitting 3 items due to poor fit),...

Frontiers in Endocrinology

Although results of animal research show that interactions between stress and sex hormones are im... more Although results of animal research show that interactions between stress and sex hormones are implicated in the development of affective disorders in women, translation of these findings to patients has been scarce. As a basic step toward advancing this field of research, we analyzed findings of studies which reported circulating cortisol levels in healthy women in the follicular vs. luteal phase of the menstrual cycle. We deemed this analysis critical not only to advance our understanding of basic physiology, but also as an important contrast to the findings of future studies evaluating stress and sex hormones in women with affective disorders. We hypothesized that cortisol levels would be lower in the follicular phase based on the proposition that changes in levels of potent GABAergic neurosteroids, including allopregnanolone, during the menstrual cycle dynamically change in the opposite direction relative to cortisol levels. Implementing strict inclusion criteria, we compiled results of high-quality studies involving 778 study participants to derive a standardized mean difference between circulating cortisol levels in the follicular vs. luteal phase of the menstrual cycle. In line with our hypothesis, our meta-analysis found that women in the follicular phase had higher cortisol levels than women in the luteal phase, with an overall Hedges' g of 0.13 (p < 0.01) for the random effects model. No significant between-study difference was detected, with the level of heterogeneity in the small range. Furthermore, there was no evidence of publication bias. As cortisol regulation is a delicate process, we review some of the basic mechanisms by which progesterone, its potent metabolites, and estradiol regulate cortisol output and circulation to contribute to the net effect of higher cortisol in the follicular phase.

Perspectives on Psychological Science

A considerable amount of recent psychological research has attributed a variety of menstrual-cycl... more A considerable amount of recent psychological research has attributed a variety of menstrual-cycle-related changes in social behavior to evolutionarily adaptive functions. Although these studies often draw interesting and unusual conclusions about female emotion and behavior within evolutionary theory, their significant limitations have not yet been addressed. In this article, we outline several methodological and conceptual issues related to the menstrual cycle that constitute threats to the internal validity and theoretical integrity of these studies. We recommend specific guidelines to address these issues and emphasize the need to apply more comprehensive and sophisticated theoretical structures when considering menstrual-cycle-related changes in emotion and behavior.

Journal of Clinical Medicine

A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated... more A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), or both are responsible for HRV fluctuations. We present the first studies to use repeated measures of E2, P4, and HRV across the cycle to model both the unique and interactive effects of person-centered E2 and P4 on HRV in multilevel models. In study one, 40 naturally-cycling participants were assessed weekly across four weeks, and were blind to the cycle focus of the study. In study two, 50 naturally-cycling participants were examined in three precisely defined cycle phases via ovulation testing. Both studies revealed that only P4 was correlated with HRV, such that higher-than-usual P4 significantly predicted lower-than-usual HRV within a given parti...

Autism Research

Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the ne... more Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the neural mechanisms subsuming reward prediction errors in ASD are poorly understood. In the current study, we investigated neural responses during social and nonsocial reward prediction errors in 22 adolescents with ASD (ages 12–17) and 20 typically developing control adolescents (ages 12–18). Participants performed a reward prediction error task using both social (i.e., faces) and nonsocial (i.e., objects) rewards during a functional magnetic resonance imaging scan. Reward prediction errors were defined in two ways: (a) the signed prediction error, the difference between the experienced and expected reward; and (b) the thresholded unsigned prediction error, the difference between expected and unexpected outcomes regardless of magnitude. During social reward prediction errors, the ASD group demonstrated the following differences relative to the TD group: (a) signed prediction error: decreased activation in the right precentral gyrus and increased activation in the right frontal pole; and (b) thresholded unsigned prediction error: increased activation in the right anterior cingulate gyrus and bilateral precentral gyrus. Groups did not differ in brain activation during nonsocial reward prediction errors. Within the ASD group, exploratory analyses revealed that reaction times and social‐communication impairments were related to precentral gyrus activation during social prediction errors. These findings elucidate the neural mechanisms of social reward prediction errors in ASD and suggest that ASD is characterized by greater neural atypicalities during social, relative to nonsocial, reward prediction errors in ASD. Autism Res 2020, 13: 715–728. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Clinical Psychological Science

Beginning at puberty, prevalence of psychopathology in females changes as their reproductive live... more Beginning at puberty, prevalence of psychopathology in females changes as their reproductive lives change. Numerous studies show steep increases in psychological problems when girls reach puberty, including spikes in depression, anxiety, aggression, delinquency, self-injurious behavior, suicidality, substance use, disordered eating, school failure, and interpersonal conflict. Clinical symptoms continue to be linked with reproductive events across women’s lives (e.g., the menstrual cycle, childbirth) and drop noticeably after menopause. These patterns are present cross-culturally and documented in numerous Western, industrialized countries, as well as the Middle East, Asia, Africa, and Latin America. Despite this, very few psychological scientists consider the interplay of reproductive change and mental health. In this introduction to the special series, we present a brief discussion of the associations between reproductive change and psychological symptoms, explore the underrepresen...

Despite a number of psychometric limitations, the Five Facet Mindfulness Questionnaire (FFMQ) is ... more Despite a number of psychometric limitations, the Five Facet Mindfulness Questionnaire (FFMQ) is one of the most widely used measures of mindfulness. Despite its potential to guide improvement of the scale, no multidimensional item response theory (IRT) analysis of the FFMQ has been conducted to date. The present studies fit competing Confirmatory Factor models to different versions of the FFMQ. A 23-item short-form of the FFMQ exhibited the most robust model-to-data fit, however, polytomous bifactor IRT exhibited poor properties, suggesting the need for scale revision. The authors undertook content revision, creating the Balanced-Inventory of Mindfulness-related Skills (BIMS). The BIMS used a structured alternative response format, wherein participants rate which of two response options is more like them, as well as the extent to which it is like them. Confirmatory factor and IRT analyses revealed reasonably good psychometric properties to a 22-item BiFactor scale, consisting of a ...

Journal of Clinical Medicine

Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variabilit... more Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variability) as a biomarker of physical and mental health has increased exponentially in recent years. However, the understanding of sources of within-person change (i.e., intra-individual variance) in CVA is lagging behind. This systematic review and meta-analysis summarizes and quantifies current empirical evidence of within-person changes in measures of CVA across the menstrual cycle in naturally-cycling premenopausal females. We conducted an extensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in five databases to identify observational studies with repeated measures of CVA in at least two menstrual cycle phases. A broad meta-analysis (nstudies = 37; nindividuals = 1,004) revealed a significant CVA decrease from the follicular to luteal phase (d = −0.39, 95% CI (−0.67, −0.11)). Furthermore, 21 studies allowed for finer-...

Eating Behaviors

OBJECTIVE Eating disorder symptoms change in a predictable pattern over the menstrual cycle such ... more OBJECTIVE Eating disorder symptoms change in a predictable pattern over the menstrual cycle such that changes in symptoms are triggered by changes in the ovarian hormones estradiol (E2) and progesterone (P4). To date, work in this area has focused exclusively on young adult women. The objective of this pilot study was to examine the effect of E2 and P4 on eating disorder symptom change in midlife women during early perimenopause. METHOD Participants included women aged 42-52 in early perimenopause (n=8). In-home self-assessments were completed for one menstrual cycle or 40-days, whichever occurred first. In-home self-assessments included collecting saliva samples each morning for E2 and P4 assays and completing online study questionnaires at the end of each day. Multilevel regression models examined the associations of E2 and P4 with daily symptoms of binge eating and body dissatisfaction. RESULTS E2 was positively associated with binge eating when P4 was high, but not when P4 was low. E2 was inversely associated with body dissatisfaction when P4 was low, but positively associated with body dissatisfaction when P4 was high. However, the simple slopes for the effect of E2 at both high and low P4 were not significant for body dissatisfaction. CONCLUSIONS Despite the pilot nature of this study, results are broadly consistent with the young adult literature indicating that P4 levels shape the impact of E2 on eating disorder symptoms. Larger studies with the inclusion of key moderators to account for individual heterogeneity are needed to confirm and extend these findings.

BMC Psychiatry , 2022

Background: Suicide is the second leading cause of death among Americans ages 10 to 34, with alar... more Background: Suicide is the second leading cause of death among Americans ages 10 to 34, with alarming recent increases in suicide rates among those assigned female at birth. A large body of evidence points to menstrual cycle influences on self-injurious thoughts and behaviors (STBs), suggesting that neurobiological hormone sensitivities, such as in premenstrual dysphoric disorder (PMDD), may drive suicide risk in females. However, existing studies of STBs in PMDD use cross-sectional self-report measures of PMDD with poor validity. As a first step to establish accurate prevalence rates of STBs in PMDD, we examined the lifetime prevalence of STBs in a large global survey of patients reporting a diagnosis of PMDD based on daily ratings. Method: Individuals with self-reported PMDD symptoms were invited to an online survey through online support groups for PMDD and social media posts from PMDD awareness accounts. Participants reported demographics, whether they had been diagnosed with PMDD by a healthcare provider using daily ratings, STBs using the Columbia Suicide Severity Rating Scale, and history of lifetime comorbid psychiatric diagnoses. Results: Of 2,689 survey completers, 599 (23%) reported a diagnosis with PMDD based on two months of daily ratings and were included in analyses. We observed high rates of lifetime active suicidal ideation (72%), planning (49%), intent (42%), preparing for an attempt (40%), and attempt (34%), as well as non-suicidal self-injury (51%). The majority (70%) of the sample reported at least one lifetime comorbid psychiatric diagnosis. Predictors of lifetime active suicidal ideation included nulliparity, low-to-moderate (vs. high) income, and history of diagnosis with major depression or post-traumatic stress disorder. Predictors of lifetime attempts among those reporting lifetime active ideation included older age, nulliparity, lower income, and history of diagnosis with post-traumatic stress disorder or borderline personality disorder. Conclusions: These data indicate high rates of STBs among those reporting prospective diagnosis of PMDD and highlight the need for prospective research on mechanisms and prevention of STBs in PMDD. Clinical practice

The Clinical psychologist, 2019

Virtual reality (VR) models allow investigators to explore high-risk situations carefully in the ... more Virtual reality (VR) models allow investigators to explore high-risk situations carefully in the laboratory using physiological assess-ment strategies and controlled conditions not available in field settings. This article introduces the use of a virtual experience to examine the influence of self-regulatory skills training on female participants ’ reactions to a high-risk encounter with an aggressive male. Sixty-three female participants were recruited for the study. Demographic data indicated that 54 % of the participants were not currently in a relationship, 36.5 % were in a committed relationship, and 9.5 % were occasionally dating. After obtaining informed consent, participants were assigned randomly to either a diaphragmatic breathing training condition or an attention con-trol condition. Results indicated that both groups rated the virtual environment as equally realistic; the aggressive advances of the male were also perceived as equally real across the two experimental grou...

Archives of Women's Mental Health

Perinatal depression affects 6.5–12.9% of women, with high rates in women of color and comorbid p... more Perinatal depression affects 6.5–12.9% of women, with high rates in women of color and comorbid perinatal anxiety in up to 50% of cases. The Research Domain Criteria (RDoC) provides a translational framework for identifying transdiagnostic psychiatric symptoms, but its application in perinatal affective disorders (PNAD) is yet limited. Here, we identified RDoC-based transdiagnostic features of PNAD in 140 primarily low-income Black and Hispanic women at 272 total longitudinal visits across the perinatal period. Women completed RDoC self-report measures of potential threat and reward valuation—Behavioral Inhibition System/Behavioral Activation System scale (BIS/BAS) and Intolerance of Uncertainty Scale (IUS)—and measures of depression (Patient Health Questionnaire-9; PHQ-9) and anxiety (Generalized Anxiety Disorder-7; GAD-7). Longitudinal mixed effects models assessed associations of between-person (“trait-like”) and within-person (“state-like”) measures of potential threat (BIS/IUS) and reward valuation (BAS-Drive) with depression and anxiety symptoms. Higher “trait-like” BIS (standardized b = 2.33, p < .001) and IUS (b = 2.97, p < .001) scores, higher “state-like” BIS (b = .71, p < .001), and lower “state-like” BAS-Drive (b = − .58, p = .04) scores were associated with worse depressive symptoms. Higher “trait-like” BIS (b = 2.22, p < .001) and IUS (b = 2.73, p < .001) and higher “state-like” BIS scores (b = .92, p < .001) were associated with worse anxiety symptoms. Potential threat may be a prominent, transdiagnostic feature of perinatal anxiety and depression, whereas reward valuation may be a non-transdiagnostic, weaker feature of perinatal depression. Potential threat is important as both a “trait-like” feature that is sustained across the perinatal period and a “state-like” feature that varies within a woman across pregnancy. Grounded in RDoC, this work reveals neurobiological targets for translational research into PNAD.

Journal of Women's Health

Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that affects ∼5% of ... more Background: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that affects ∼5% of menstruating individuals. Although symptoms are limited to the luteal phase of the menstrual cycle, PMDD causes significant distress and impairment across a range of activities. PMDD is under-recognized by health care providers, can be difficult to diagnose, and lies at the intersection of gynecology and psychiatry. Thus, many patients are misdiagnosed, or encounter challenges in seeking care. The aim of this study was to examine patients' experiences with different health care specialties when seeking care for PMDD symptoms. Methods: We examined data from the 2018 Global Survey of Premenstrual Disorders conducted by the International Association for Premenstrual Disorders (IAPMD). Patients rated their health care providers (general practitioners, psychiatrists, gynecologists, psychotherapists) in three key areas related to treatment of premenstrual mood complaints: interpersonal factors, awareness and knowledge of PMDD, and whether the patient was asked to track symptoms daily. Intraclass correlations examined between- and within-person variance. Multilevel regression models predicted ratings on each provider competency item, with ratings nested within individuals to examine the within-patient effect of provider type on outcomes. Results: The sample included 2,512 patients who reported seeking care for PMDD symptoms. Regarding interpersonal factors, psychotherapists were generally rated the highest. On awareness and knowledge of PMDD, gynecologists and psychiatrists were generally rated the highest. Gynecologists were more likely than other providers to ask patients to track symptoms daily. Conclusions: These findings suggest that different providers have different strengths in assessing and treating PMDD. Further, graduate and medical training programs may benefit from increased curricular development regarding evidence-based evaluation and treatment of PMDD.

Psychoneuroendocrinology

Progesterone (P4) can be metabolized to two general classes of neuroactive steroids (NAS) -those ... more Progesterone (P4) can be metabolized to two general classes of neuroactive steroids (NAS) -those like allopregnanolone (ALLO) and pregnanolone (PA) which are positive allosteric modulators of the Gamma Aminobutyric Acid type A (GABAA) receptor and those like isoallopregnanolone (ISOALLO) and epipregnanolone (EPI) which are negative allosteric modulators of the GABAA receptor. While exogenous administration of ALLO is effective in treating postpartum depression, knowledge gaps remain in the dynamic interplay of NAS across the perinatal period. In particular little is known about ALLO and PA in relation to depression earlier in pregnancy, and the role of ISOALLO and EPI in relation to depression at any point in the perinatal period. In a prospective, nested case/control study in low-income women of color, we compared the metabolism of P4 to four NAS (i.e., ratios ALLO:P4, PA:P4, ISOALLO:P4, EPI:P4) in pregnant women with depression at either or both of the first and second trimesters (cases) and women without depression at either time point (controls). Fifty women (36% depressed, 56% Black, 28% Latina) completed depression screening using a computerized adaptive test of mental health (CAT-MH™) and provided blood serum samples in both trimesters. In longitudinal mixed effects models of both trimesters, PND cases showed higher ratios of ALLO:P4 (p = .002) and PA:P4 (p = .03) compared to controls. In regression models of only first trimester data, there was no significant difference in NAS ratios between cases and controls (p > .05). Conversely, in models of the second trimester, ratios of PA:P4 (p = .002) and ISOALLO:P4 (p = .01) were significantly higher in cases compared to controls, and ratios of ALLO:P4 (p = .08) and EPI:P4 (p = .1) also trended higher in cases. The most severe cases, those with depression at both trimesters, showed an increase in ALLO:P4 (p = .06) and EPI:P4 (p < .001) ratios from the first to the second trimester, whereas controls showed a decrease in these ratios. Secondary analyses confirmed higher levels of ALLO (p = .04) and PA (p = .07) overall in cases compared to controls, along with higher levels of PA (p = .005) and ISOALLO (p = .02) in the second trimester alone. This work suggests a dynamic relationship between NAS and PND; whereas low ALLO levels have been previously associated with postpartum depression, earlier in pregnancy a higher metabolism of P4 to ALLO (and higher ALLO levels) is associated with depression. Some women may show a hormone-sensitive depressive response to acute increases in NAS metabolism in early pregnancy.

Journal of Affective Disorders

Abstract Background : Accumulating evidence indicates that reduced activity within the monoamine ... more Abstract Background : Accumulating evidence indicates that reduced activity within the monoamine systems contributes to the pathophysiology of major depressive disorder (MDD) and suicide. In this study, we have tested the hypothesis that monoaminergic gene transcription is abnormally regulated in MDD and suicide. Methods : The transcription of specific monoaminergic genes was quantified by qPCR in the dorsolateral prefrontal cortex (DLPFC) of postmortem MDD subjects (n=80) and non-psychiatric controls (CTRL, n=32). Transcripts measured included monoaminergic transporters (the serotonin transporter (SERT), norepinephrine transporter (NET), dopamine transporter (DAT), plasma monoamine transporter (PMAT), vesicular monoamine transporter (VMAT)) and the tryptophan hydroxylase (TPH) enzymes, TPH1 and TPH2). We tested for transcriptional differences between diagnostic groups in addition to testing for differences specific to the depressed suicides. Results : Multivariate analysis of monoaminergic gene transcription revealed a sex by diagnosis interaction (F8,99=2.87, p=0.007). We report lower VMAT1 and PMAT expression in depressed males, and conversely higher VMAT2, TPH2 and NET expression in depressed females, relative to controls of the same sex (p Limitations : Gene expression measures were not associated with the presence of antidepressant medication. Nevertheless, to minimize the impact of medication status and other potential confounding variables, these were included as covariates in our analyses. Conclusions : We report sex differences in the transcription of monoaminergic genes in the DLPFC in MDD. Therefore abnormalities of monoaminergic gene expression may contribute to altered DLPFC activity exhibited in major depression.

Objectives: The goal of the current study was to refine and validate a revision of the Five Facet... more Objectives: The goal of the current study was to refine and validate a revision of the Five FacetMindfulness Questionnaire (FFMQ), with the goal of retaining its useful features and mitigatingthose features that have been identified to be problematic.Methods: A 30-item pilot version of the Balanced Inventory of Mindfulness-related Skills(BIMS) was developed by implementing the structured alternative item format (presenting bothpositive and negative aspects of each item) and revising the wording of items. Herein, wecollected data from a convenience sample of n=1,014 individuals, reduced to n=757 after datacleaning. We conducted exploratory factor analysis (EFA) and confirmatory factor analyses(CFA) on randomly separated subsets of the sample and explored response patterns andcorrelations with relevant measures (including a short-form of the FFMQ).Results: Parallel analysis and EFA indicated a five-factor, correlated structure across a final 27items (omitting 3 items due to poor fit),...

Frontiers in Endocrinology

Although results of animal research show that interactions between stress and sex hormones are im... more Although results of animal research show that interactions between stress and sex hormones are implicated in the development of affective disorders in women, translation of these findings to patients has been scarce. As a basic step toward advancing this field of research, we analyzed findings of studies which reported circulating cortisol levels in healthy women in the follicular vs. luteal phase of the menstrual cycle. We deemed this analysis critical not only to advance our understanding of basic physiology, but also as an important contrast to the findings of future studies evaluating stress and sex hormones in women with affective disorders. We hypothesized that cortisol levels would be lower in the follicular phase based on the proposition that changes in levels of potent GABAergic neurosteroids, including allopregnanolone, during the menstrual cycle dynamically change in the opposite direction relative to cortisol levels. Implementing strict inclusion criteria, we compiled results of high-quality studies involving 778 study participants to derive a standardized mean difference between circulating cortisol levels in the follicular vs. luteal phase of the menstrual cycle. In line with our hypothesis, our meta-analysis found that women in the follicular phase had higher cortisol levels than women in the luteal phase, with an overall Hedges' g of 0.13 (p < 0.01) for the random effects model. No significant between-study difference was detected, with the level of heterogeneity in the small range. Furthermore, there was no evidence of publication bias. As cortisol regulation is a delicate process, we review some of the basic mechanisms by which progesterone, its potent metabolites, and estradiol regulate cortisol output and circulation to contribute to the net effect of higher cortisol in the follicular phase.

Perspectives on Psychological Science

A considerable amount of recent psychological research has attributed a variety of menstrual-cycl... more A considerable amount of recent psychological research has attributed a variety of menstrual-cycle-related changes in social behavior to evolutionarily adaptive functions. Although these studies often draw interesting and unusual conclusions about female emotion and behavior within evolutionary theory, their significant limitations have not yet been addressed. In this article, we outline several methodological and conceptual issues related to the menstrual cycle that constitute threats to the internal validity and theoretical integrity of these studies. We recommend specific guidelines to address these issues and emphasize the need to apply more comprehensive and sophisticated theoretical structures when considering menstrual-cycle-related changes in emotion and behavior.

Journal of Clinical Medicine

A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated... more A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), or both are responsible for HRV fluctuations. We present the first studies to use repeated measures of E2, P4, and HRV across the cycle to model both the unique and interactive effects of person-centered E2 and P4 on HRV in multilevel models. In study one, 40 naturally-cycling participants were assessed weekly across four weeks, and were blind to the cycle focus of the study. In study two, 50 naturally-cycling participants were examined in three precisely defined cycle phases via ovulation testing. Both studies revealed that only P4 was correlated with HRV, such that higher-than-usual P4 significantly predicted lower-than-usual HRV within a given parti...

Autism Research

Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the ne... more Autism spectrum disorder (ASD) is characterized by impaired predictive abilities; however, the neural mechanisms subsuming reward prediction errors in ASD are poorly understood. In the current study, we investigated neural responses during social and nonsocial reward prediction errors in 22 adolescents with ASD (ages 12–17) and 20 typically developing control adolescents (ages 12–18). Participants performed a reward prediction error task using both social (i.e., faces) and nonsocial (i.e., objects) rewards during a functional magnetic resonance imaging scan. Reward prediction errors were defined in two ways: (a) the signed prediction error, the difference between the experienced and expected reward; and (b) the thresholded unsigned prediction error, the difference between expected and unexpected outcomes regardless of magnitude. During social reward prediction errors, the ASD group demonstrated the following differences relative to the TD group: (a) signed prediction error: decreased activation in the right precentral gyrus and increased activation in the right frontal pole; and (b) thresholded unsigned prediction error: increased activation in the right anterior cingulate gyrus and bilateral precentral gyrus. Groups did not differ in brain activation during nonsocial reward prediction errors. Within the ASD group, exploratory analyses revealed that reaction times and social‐communication impairments were related to precentral gyrus activation during social prediction errors. These findings elucidate the neural mechanisms of social reward prediction errors in ASD and suggest that ASD is characterized by greater neural atypicalities during social, relative to nonsocial, reward prediction errors in ASD. Autism Res 2020, 13: 715–728. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Clinical Psychological Science

Beginning at puberty, prevalence of psychopathology in females changes as their reproductive live... more Beginning at puberty, prevalence of psychopathology in females changes as their reproductive lives change. Numerous studies show steep increases in psychological problems when girls reach puberty, including spikes in depression, anxiety, aggression, delinquency, self-injurious behavior, suicidality, substance use, disordered eating, school failure, and interpersonal conflict. Clinical symptoms continue to be linked with reproductive events across women’s lives (e.g., the menstrual cycle, childbirth) and drop noticeably after menopause. These patterns are present cross-culturally and documented in numerous Western, industrialized countries, as well as the Middle East, Asia, Africa, and Latin America. Despite this, very few psychological scientists consider the interplay of reproductive change and mental health. In this introduction to the special series, we present a brief discussion of the associations between reproductive change and psychological symptoms, explore the underrepresen...

Despite a number of psychometric limitations, the Five Facet Mindfulness Questionnaire (FFMQ) is ... more Despite a number of psychometric limitations, the Five Facet Mindfulness Questionnaire (FFMQ) is one of the most widely used measures of mindfulness. Despite its potential to guide improvement of the scale, no multidimensional item response theory (IRT) analysis of the FFMQ has been conducted to date. The present studies fit competing Confirmatory Factor models to different versions of the FFMQ. A 23-item short-form of the FFMQ exhibited the most robust model-to-data fit, however, polytomous bifactor IRT exhibited poor properties, suggesting the need for scale revision. The authors undertook content revision, creating the Balanced-Inventory of Mindfulness-related Skills (BIMS). The BIMS used a structured alternative response format, wherein participants rate which of two response options is more like them, as well as the extent to which it is like them. Confirmatory factor and IRT analyses revealed reasonably good psychometric properties to a 22-item BiFactor scale, consisting of a ...

Journal of Clinical Medicine

Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variabilit... more Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variability) as a biomarker of physical and mental health has increased exponentially in recent years. However, the understanding of sources of within-person change (i.e., intra-individual variance) in CVA is lagging behind. This systematic review and meta-analysis summarizes and quantifies current empirical evidence of within-person changes in measures of CVA across the menstrual cycle in naturally-cycling premenopausal females. We conducted an extensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in five databases to identify observational studies with repeated measures of CVA in at least two menstrual cycle phases. A broad meta-analysis (nstudies = 37; nindividuals = 1,004) revealed a significant CVA decrease from the follicular to luteal phase (d = −0.39, 95% CI (−0.67, −0.11)). Furthermore, 21 studies allowed for finer-...

Eating Behaviors

OBJECTIVE Eating disorder symptoms change in a predictable pattern over the menstrual cycle such ... more OBJECTIVE Eating disorder symptoms change in a predictable pattern over the menstrual cycle such that changes in symptoms are triggered by changes in the ovarian hormones estradiol (E2) and progesterone (P4). To date, work in this area has focused exclusively on young adult women. The objective of this pilot study was to examine the effect of E2 and P4 on eating disorder symptom change in midlife women during early perimenopause. METHOD Participants included women aged 42-52 in early perimenopause (n=8). In-home self-assessments were completed for one menstrual cycle or 40-days, whichever occurred first. In-home self-assessments included collecting saliva samples each morning for E2 and P4 assays and completing online study questionnaires at the end of each day. Multilevel regression models examined the associations of E2 and P4 with daily symptoms of binge eating and body dissatisfaction. RESULTS E2 was positively associated with binge eating when P4 was high, but not when P4 was low. E2 was inversely associated with body dissatisfaction when P4 was low, but positively associated with body dissatisfaction when P4 was high. However, the simple slopes for the effect of E2 at both high and low P4 were not significant for body dissatisfaction. CONCLUSIONS Despite the pilot nature of this study, results are broadly consistent with the young adult literature indicating that P4 levels shape the impact of E2 on eating disorder symptoms. Larger studies with the inclusion of key moderators to account for individual heterogeneity are needed to confirm and extend these findings.

Biological psychology, Jan 30, 2015

Cyclical fluctuations in the ovarian hormones 17β-estradiol (E2; estrogen) and progesterone (P4) ... more Cyclical fluctuations in the ovarian hormones 17β-estradiol (E2; estrogen) and progesterone (P4) predict emotions, cognitive processes, and behaviors relevant to Borderline Personality Disorder (BPD); however, there are individual differences in sensitivity to normal hormone shifts. This study examined associations of naturally occurring hormonal changes with concurrent BPD feature expression. Forty women sampled for a flat distribution of the PAI-BOR (n=10 where T<50, n=10 where 50<T<60, n=10 where 60<T<70, and n=10 where T>70) provided 4 weekly saliva samples and psychological assessments. Across most outcomes (e.g., BPD features, felt rejection, anger rumination, negative urgency) P4 deviation (from one's person mean) moderated the effect of current E2 deviation (from one's person mean) among women high (+1 SD) in trait BPD features such that E2 deviation was negatively associated with symptoms only when P4 was higher-than-usual. Cyclical hormone changes...