Publications by authors named "Crystal Edler Schiller"

12 Publications

  • Page 1 of 1

Reduction in left frontal alpha oscillations by transcranial alternating current stimulation in major depressive disorder is context-dependent in a randomized clinical trial.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jul 14. Epub 2021 Jul 14.

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC; Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address:

Background: Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for non-invasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind placebo controlled clinical trial.

Methods: In this current study, we aimed to replicate successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. 84 participants were randomized to receive verum or sham IAF-tACS. Electrical brain activity was recorded during rest and while viewing emotionally-salient images before and after stimulation to investigate if the modulation of alpha oscillation by tACS exhibited specificity with regards to valence.

Results: In agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared to placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants.

Conclusion: Together these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD.
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http://dx.doi.org/10.1016/j.bpsc.2021.07.001DOI Listing
July 2021

Perinatal mental health around the world: priorities for research and service development in the USA.

BJPsych Int 2020 Nov;17(4):87-91

Professor, Department of Psychological and Brain Sciences, University of Iowa, USA. Email:

The perinatal mental health field is growing rapidly, which has yielded innovations in both prevention and treatment. To realise the potential of these innovations to transform clinical practice, further investment in research and clinical service development is required. Clinical services must be expanded by providing increased access to specialty care and education for front-line clinicians. Research is needed to develop a personalised medicine approach to understanding the complex aetiologies of perinatal depression and optimising treatments to promote both remission and long-term recovery. Such initiatives will require policies to prioritise federal research funding and healthcare coverage for perinatal depression.
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http://dx.doi.org/10.1192/bji.2020.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609989PMC
November 2020

Acceptance and commitment therapy for perinatal mood and anxiety disorders: development of an inpatient group intervention.

Arch Womens Ment Health 2017 10 10;20(5):645-654. Epub 2017 Jun 10.

UNC Department of Psychiatry, 101 Manning Drive, Campus Box #7160, Chapel Hill, NC, 27599-7160, USA.

Perinatal mood and anxiety disorders are a leading cause of morbidity and mortality for childbearing women. Current treatments, such as cognitive behavioral therapy and interpersonal therapy, have demonstrated modest success in addressing perinatal psychiatric symptoms; however, additional treatment options are needed to address the limitations of current approaches, particularly for women experiencing moderate to severe perinatal mental illness during pregnancy or postpartum. We discuss the use of acceptance and commitment therapy (ACT) as a promising treatment approach that may be uniquely suited for perinatal women due to its emphasis of values, mindfulness, and acceptance; these psychological constructs notably address the significant psychiatric and behavioral health condition comorbidity, somatic symptoms, and stigma associated with perinatal mood and anxiety disorders. In addition, we describe the development of a four-session ACT-based group intervention at the Perinatal Psychiatry Inpatient Unit at the University of North Carolina at Chapel Hill. Sessions focus on core ACT processes of acceptance, cognitive defusion, present-moment awareness, value identification, and goal setting, and we describe how each of these processes is relevant to the perinatal population. Implications for future clinical applications and research investigations are discussed.
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http://dx.doi.org/10.1007/s00737-017-0735-8DOI Listing
October 2017

Reproductive Steroid Regulation of Mood and Behavior.

Compr Physiol 2016 06 13;6(3):1135-60. Epub 2016 Jun 13.

Psychiatry Department, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

In this article, we examine evidence supporting the role of reproductive steroids in the regulation of mood and behavior in women and the nature of that role. In the first half of the article, we review evidence for the following: (i) the reproductive system is designed to regulate behavior; (ii) from the subcellular to cellular to circuit to behavior, reproductive steroids are powerful neuroregulators; (iii) affective disorders are disorders of behavioral state; and (iv) reproductive steroids affect virtually every system implicated in the pathophysiology of depression. In the second half of the article, we discuss the diagnosis of the three reproductive endocrine-related mood disorders (premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression) and present evidence supporting the relevance of reproductive steroids to these conditions. Existing evidence suggests that changes in reproductive steroid levels during specific reproductive states (i.e., the premenstrual phase of the menstrual cycle, pregnancy, parturition, and the menopause transition) trigger affective dysregulation in susceptible women, thus suggesting the etiopathogenic relevance of these hormonal changes in reproductive mood disorders. Understanding the source of individual susceptibility is critical to both preventing the onset of illness and developing novel, individualized treatments for reproductive-related affective dysregulation. © 2016 American Physiological Society. Compr Physiol 6:1135-1160, 2016e.
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http://dx.doi.org/10.1002/cphy.c150014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309888PMC
June 2016

Resting-state connectivity predictors of response to psychotherapy in major depressive disorder.

Neuropsychopharmacology 2015 Jun 12;40(7):1659-73. Epub 2015 Jan 12.

1] UNC Neurobiology Curriculum, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA [2] Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA [3] Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA [4] Duke-UNC Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, USA.

Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment connectivity of the right insula with the right middle temporal gyrus and the left intraparietal sulcus with the orbital frontal cortex. These results add to the nascent body of literature investigating pretreatment rs-fcMRI predictors of antidepressant treatment response and is the first study to examine rs-fcMRI predictors of response to psychotherapy.
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http://dx.doi.org/10.1038/npp.2015.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915248PMC
June 2015

The role of reproductive hormones in postpartum depression.

CNS Spectr 2015 Feb 29;20(1):48-59. Epub 2014 Sep 29.

Psychiatry Department,University of North Carolina at Chapel Hill,Chapel Hill,North Carolina,USA.

Despite decades of research aimed at identifying the causes of postpartum depression (PPD), PPD remains common, and the causes are poorly understood. Many have attributed the onset of PPD to the rapid perinatal change in reproductive hormones. Although a number of human and nonhuman animal studies support the role of reproductive hormones in PPD, several studies have failed to detect an association between hormone concentrations and PPD. The purpose of this review is to examine the hypothesis that fluctuations in reproductive hormone levels during pregnancy and the postpartum period trigger PPD in susceptible women. We discuss and integrate the literature on animal models of PPD and human studies of reproductive hormones and PPD. We also discuss alternative biological models of PPD to demonstrate the potential for multiple PPD phenotypes and to describe the complex interplay of changing reproductive hormones and alterations in thyroid function, immune function, hypothalamic-pituitary-adrenal (HPA) axis function, lactogenic hormones, and genetic expression that may contribute to affective dysfunction. There are 3 primary lines of inquiry that have addressed the role of reproductive hormones in PPD: nonhuman animal studies, correlational studies of postpartum hormone levels and mood symptoms, and hormone manipulation studies. Reproductive hormones influence virtually every biological system implicated in PPD, and a subgroup of women seem to be particularly sensitive to the effects of perinatal changes in hormone levels. We propose that these women constitute a "hormone-sensitive" PPD phenotype, which should be studied independent of other PPD phenotypes to identify underlying pathophysiology and develop novel treatment targets.
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http://dx.doi.org/10.1017/S1092852914000480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363269PMC
February 2015

Allopregnanolone as a mediator of affective switching in reproductive mood disorders.

Psychopharmacology (Berl) 2014 Sep 21;231(17):3557-67. Epub 2014 May 21.

Department of Psychiatry, University of North Carolina at Chapel Hill, 250 Medical School Wing D, Campus Box #7175, Chapel Hill, NC, 27599-7175, USA,

Rationale: Reproductive mood disorders, including premenstrual dysphoria (PMD) and postpartum depression (PPD), are characterized by affective dysregulation that occurs during specific reproductive states. The occurrence of illness onset during changes in reproductive endocrine function has generated interest in the role of gonadal steroids in the pathophysiology of reproductive mood disorders, yet the mechanisms by which the changing hormone milieu triggers depression in susceptible women remain poorly understood.

Objectives: This review focuses on one of the neurosteroid metabolites of progesterone - allopregnanolone (ALLO) - that acutely regulates neuronal function and may mediate affective dysregulation that occurs concomitant with changes in reproductive endocrine function. We describe the role of the "neuroactive" steroids estradiol and progesterone in reproductive endocrine-related mood disorders to highlight the potential mechanisms by which ALLO might contribute to their pathophysiology. Finally, using existing data, we test the hypothesis that changes in ALLO levels may trigger affective dysregulation in susceptible women.

Results: Although there is no reliable evidence that basal ALLO levels distinguish those with PMD or PPD from those without, existing animal models suggest potential mechanisms by which specific reproductive states may unmask susceptibility to affective dysregulation. Consistent with these models, initially euthymic women with PMD and those with a history of PPD show a negative association between depressive symptoms and circulating ALLO levels following progesterone administration.

Conclusions: Existing animal models and our own preliminary data suggest that ALLO may play an important role in the pathophysiology of reproductive mood disorders by triggering affective dysregulation in susceptible women.
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http://dx.doi.org/10.1007/s00213-014-3599-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135022PMC
September 2014

Remitted major depression is characterized by reduced prefrontal cortex reactivity to reward loss.

J Affect Disord 2013 Nov 5;151(2):756-762. Epub 2013 Jul 5.

Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, United States; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, United States; Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, United States; Duke-UNC Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC 27710, United States.

Background: Major depression (MDD) is characterized by anhedonia. Although a growing body of literature has linked anhedonia in MDD to reduced frontostriatal activity during reward gains, relatively few studies have examined neural responsivity to loss, and no studies to date have examined neural responses to loss in euthymic individuals with a history of MDD.

Methods: An fMRI monetary incentive delay task was administered to 19 participants with remitted MDD (rMDD) and 19 never depressed controls. Analyses examined group activation differences in brain reward circuitry during monetary loss anticipation and outcomes. Secondary analyses examined the association between self-reported rumination and brain activation in the rMDD group.

Results: Compared to controls, the rMDD group showed less superior frontal gyrus activation during loss anticipation and less inferior and superior frontal gyri activation during loss outcomes (cluster corrected p's<.05). Ruminative Responses Scale scores were negatively correlated with superior frontal gyrus activation (r=-.68, p=.001) during loss outcomes in the rMDD group.

Limitations: Replication with a larger sample is needed.

Conclusions: Euthymic individuals with a history of MDD showed prefrontal cortex hypoactivation during loss anticipation and outcomes, and the degree of superior frontal gyrus hypoactivation was associated with rumination. Abnormal prefrontal cortex responses to loss may reflect a trait-like vulnerability to MDD, although future research is needed to evaluate the utility of this functional neural endophenotype as a prospective risk marker.
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http://dx.doi.org/10.1016/j.jad.2013.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797197PMC
November 2013

Neural mechanisms of cognitive reappraisal in remitted major depressive disorder.

J Affect Disord 2013 Oct 21;151(1):171-7. Epub 2013 Jun 21.

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.

Background: Down-regulation of negative emotions by cognitive strategies relies on prefrontal cortical modulation of limbic brain regions, and impaired frontolimbic functioning during cognitive reappraisal has been observed in affective disorders. However, no study to date has examined cognitive reappraisal in unmedicated euthymic individuals with a history of major depressive disorder relative to symptom-matched controls. Given that a history of depression is a critical risk factor for future depressive episodes, investigating the neural mechanisms of emotion regulation in remitted major depressive disorder (rMDD) may yield novel insights into depression risk.

Method: We assessed 37 individuals (18 rMDD, 19 controls) with functional magnetic resonance imaging (fMRI) during a task requiring cognitive reappraisal of sad images.

Results: Both groups demonstrated decreased self-reported negative affect after cognitive reappraisal and no group differences in the effects of cognitive reappraisal on mood were evident. Functional MRI results indicated greater paracingulate gyrus (rostral anterior cingulate cortex, Brodmann area 32) activation and decreased right midfrontal gyrus (Brodmann area 6) activation during the reappraisal of sad images.

Limitations: Trial-by-trial ratings of pre-regulation affect were not collected, limiting the interpretation of post-regulation negative affect scores.

Conclusions: Results suggest that activation of rostral anterior cingulate cortex, a region linked to the prediction of antidepressant treatment response, and of the right midfrontal gyrus, a region involved in cognitive control in the context of cognitive reappraisal, may represent endophenotypic markers of future depression risk. Future prospective studies will be needed to validate the predictive utility of these neural markers.
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http://dx.doi.org/10.1016/j.jad.2013.05.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769423PMC
October 2013

Estradiol modulates anhedonia and behavioral despair in rats and negative affect in a subgroup of women at high risk for postpartum depression.

Physiol Behav 2013 Jul 13;119:137-44. Epub 2013 Jun 13.

Department of Psychiatry, University of North Carolina at Chapel Hill, 10514 Neurosciences Hospital, 101 Manning Drive, Campus Box 7160, Chapel Hill, NC 27599-7160, USA.

In an effort to address inconsistencies in the literature, we tested a cross-species estrogen withdrawal model of postpartum depression (PPD) with a series of rodent experiments and a prospective, naturalistic human study. All rats were ovariectomized prior to experimentation. The first rat experiment examined the effects of low- and high-dose estradiol administration and withdrawal on lateral-hypothalamic self-stimulation, a behavioral index of anhedonia, in experimental (n=7) and vehicle-only control animals (n=7). The second rat experiment examined the effects of high-dose estradiol withdrawal on activity and immobility during the forced swim test, an index of behavioral despair, in a separate group of experimental (n=8) and vehicle-only control animals (n=8). In the human study, women with (n=8) and without (n=12) a history of PPD completed mood ratings and collected saliva samples (to assess estradiol levels) daily during the third trimester of pregnancy through 10 days postpartum. The presence of PPD was assessed at one month postpartum. In the animal studies, rats in the estradiol withdrawal group demonstrated significantly greater immobility and less swimming than controls. Estradiol withdrawal resulted in reduced responding for electrical stimulation (multiple intensities) relative to estradiol administration. In the human study, there was no significant association between estradiol and negative affect among women with or without a history of PPD. However, there was a correlation between daily estradiol levels and negative affect in the women with incident PPD at one month postpartum. Despite important cross-species differences, both the rat and human studies provided evidence of the effects of estradiol on perinatal depressive symptoms.
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http://dx.doi.org/10.1016/j.physbeh.2013.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772627PMC
July 2013

Association between ovarian hormones and smoking behavior in women.

Exp Clin Psychopharmacol 2012 Aug 30;20(4):251-7. Epub 2012 Apr 30.

Department of Psychiatry.

Studies examining the association between menstrual cycle phases and smoking behavior in women have yielded mixed results. The purpose of this study was to elucidate the associations between ovarian hormones and smoking by directly measuring ovarian hormone levels and obtaining a laboratory assessment of smoking behaviors. Four hypotheses were tested: Increased smoking will be associated with (1) low absolute levels of estradiol and progesterone; (2) decreasing (i.e., dynamic changes in) estradiol and progesterone; (3) lower ratios of progesterone to estradiol; and (4) higher ratios of estradiol to progesterone. Female smokers (≥10 cigarettes/day) with regular menstrual cycles were recruited as part of a larger, ongoing study examining the influence of ovarian hormones on smoking cessation treatment. Participants completed 2 study visits, including a 1-hr ad lib smoking topography session, which provided a detailed assessment of smoking behavior. Both the change in hormone levels over time and the relative ratios of ovarian hormones were associated with smoking behavior, but each to a limited extent. Decreases in estradiol (r = -.21, p = .048) and decreases in progesterone (r = -.23, p = .03) were associated with increased puff intensity. Lower ratios of progesterone to estradiol were associated with a greater number of puffs (r = -.26, p = .01) and weight of cigarettes smoked (r = -.29, p = .005). The best predictors of smoking behavior were the ratio of progesterone to estradiol (z = -2.7, p = .004) and the change in estradiol and progesterone over time (z = -2.1, p = .02). This pattern of results may help to explain inconsistent findings in previous studies and suggest potential mechanisms by which hormones influence nicotine addiction.
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http://dx.doi.org/10.1037/a0027759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660106PMC
August 2012

Depression and anxiety among postpartum and adoptive mothers.

Arch Womens Ment Health 2011 Aug 3;14(4):335-43. Epub 2011 Jul 3.

University of Iowa, Iowa City, IA, USA.

Similar to biological mothers during the postpartum period, women who adopt children experience increased stress and life changes that may put them at risk for developing depression and anxiety. The purpose of the current study was to compare levels of depression and anxiety symptoms between postpartum and adoptive women and, among adoptive women, to examine associations between specific stressors and depressive symptoms. Data from adoptive mothers (n = 147), recruited from Holt International, were compared to existing data from postpartum women (n = 147). Differences in the level of depression and anxiety symptoms as measured by the Inventory of Depression and Anxiety Symptoms among postpartum and adoptive women were examined. Associations between specific stressors and depressive symptoms were examined among adoptive mothers. Postpartum and adoptive women had comparable levels of depressive symptoms, but adoptive women reported greater well-being and less anxiety than postpartum women. Stressors (e.g., sleep deprivation, history of infertility, past psychological disorder, and less marital satisfaction) were all significantly associated with depressive symptoms among adoptive women. The level of depressive symptoms was not significantly different between the two groups. In contrast, adoptive women experienced significantly fewer symptoms of anxiety and experienced greater well-being. Additionally, adoptive mothers experienced more depressive symptoms during the year following adoption when the stressors were present. Thus, women with these characteristics should be routinely screened for depression and anxiety.
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http://dx.doi.org/10.1007/s00737-011-0227-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433270PMC
August 2011
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