Catherine Monk

Maternal stress responses and anxiety during pregnancy: effects on fetal heart rate.

This study examined the effect of an acute maternal stress response and anxiety on fetal heart rate. Seventeen healthy, 3rd-trimester pregnant women (mean age = 26 +/- 6 years) were instrumented for continuous electrocardiography, blood pressure (BP), respiration, and fetal heart rate (HR). Subjects completed the state anxiety subscale of the State Trait Personality Inventory (STPI), then rested quietly in a semirecumbent position for a 5-min baseline period, followed by either a 5-min arithmetic or Stroop color-word task. Over the entire 5-min stress period and when averaged across all subjects, the stressors led to significant increases in maternal systolic BP and respiratory rate but changes in maternal HR, diastolic BP, and fetal HR were not significant. However, when subjects were dichotomized into groups that had above or below average anxiety scores [ANX(+) and ANX(-)], both groups had similar respiration rate increases to the stressors, but the BP and fetal heart rate (FHR) responses were significantly different. Women in the ANX(-) group had significantly greater BP responses compared to women in the ANX(+) group whereas the fetuses of ANX(+) women showed significant HR increases and the fetuses of ANX(-) women exhibited nonsignificant decreases. These findings suggest that womens acute emotional reactivity during pregnancy can influence fetal HR patterns and that a stress-induced increase in maternal BP is not the primary signal by which a womens stress response is transduced to her fetus. The results are consistent with the hypothesis that maternal psychological variables may shape the neurobehavioral development of the fetus.

Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways

Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with risk of psychopathology. Although the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this article, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress.

Epigenetic Effects of Prenatal Stress on 11β-Hydroxysteroid Dehydrogenase-2 in the Placenta and Fetal Brain

Maternal exposure to stress during pregnancy is associated with significant alterations in offspring neurodevelopment and elevated maternal glucocorticoids likely play a central role in mediating these effects. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers the impact of maternal glucocorticoid exposure by converting cortisol/corticosterone into inactive metabolites. However, previous studies indicate that maternal adversity during the prenatal period can lead to a down-regulation of this enzyme. In the current study, we examined the impact of prenatal stress (chronic restraint stress during gestational days 14–20) in Long Evans rats on HSD11B2 mRNA in the placenta and fetal brain (E20) and assessed the role of epigenetic mechanisms in these stress-induced effects. In the placenta, prenatal stress was associated with a significant decrease in HSD11B2 mRNA, increased mRNA levels of the DNA methyltransferase DNMT3a, and increased DNA methylation at specific CpG sites within the HSD11B2 gene promoter. Within the fetal hypothalamus, though we find no stress-induced effects on HSD11B2 mRNA levels, prenatal stress induced decreased CpG methylation within the HSD11B2 promoter and increased methylation at sites within exon 1. Within the fetal cortex, HSD11B2 mRNA and DNA methylation levels were not altered by prenatal stress, though we did find stress-induced elevations in DNMT1 mRNA in this brain region. Within individuals, we identified CpG sites within the HSD11B2 gene promoter and exon 1 at which DNA methylation levels were highly correlated between the placenta and fetal cortex. Overall, our findings implicate DNA methylation as a mechanism by which prenatal stress alters HSD11B2 gene expression. These findings highlight the tissue specificity of epigenetic effects, but also raise the intriguing possibility of using the epigenetic status of placenta to predict corresponding changes in the brain.

Fetal heart rate reactivity differs by women's psychiatric status: An early marker for developmental risk?

OBJECTIVE To determine whether there are differences in fetal heart rate (FHR) reactivity associated with womens psychiatric status. METHOD In 57 women in their 36th to 38th week of pregnancy (mean age 27 +/- 6 years), electrocardiogram, blood pressure (BP), respiration (RSP), and FHR were measured during baseline and a psychological challenge (a Stroop color-word matching task). Subjects underwent the Structured Clinical Interview for DSM-IV (SCID) and completed the Spielberger State-Trait Anxiety Inventory prior to testing. RESULTS There was a significant main effect of maternal diagnostic group on FHR reactivity during the Stroop task even after controlling for birth weight and womens BP reactivity (F4,44 = 2.68, p =.04). Fetuses of depressed women had greater heart rate increases compared to fetuses of women with anxiety disorders and those of healthy, low-anxiety women (post hoc comparisons using the Fisher protected least significant difference test; t = 4.12, p <.05; t = 4.72, p <.01, respectively). There was a similar pattern comparing fetuses of healthy, high-anxiety women to the same two groups (t = 3.29, p <.05; t = 3.99, p <.05, respectively). There were no group differences in FHR during a resting baseline period (F4,52 = 1.2, p =.35). CONCLUSIONS Maternal mood disturbance is associated with alterations in childrens physiological reactivity prior to birth.

Enhanced stress reactivity in paediatric anxiety disorders: implications for future cardiovascular health

The aim was to clarify the developmental nature of associations between psychiatric illness and risk for cardiovascular disease by investigating differences in cardiac functioning between youth with anxiety disorders and healthy controls. Twenty-two children meeting DSM-IV criteria for either separation anxiety disorder, overanxious disorder, panic disorder/panic attacks, or social phobia and 12 healthy controls underwent continuous electrocardiogram and respiration rate monitoring during a 15 min baseline period and 15 min of exposure to 5% CO(2). Heart rate (HR) and high frequency heart rate variability (HRV), a non-invasive measure of cardiac parasympathetic control, were calculated. Youth with anxiety disorders had higher and less fluctuating HR during baseline. Data also suggested that probands showed diminished overall changes in HRV during baseline and CO(2) inhalation relative to controls. However, as respiration rate affects HRV, these findings were confounded by changes in respiration elicited by CO(2) inhalation. The data suggest that youth with anxiety disorders experience an elevated and less fluctuating HR in the face of a novel situation, possibly due to a failure to appropriately modulate HRV. In adults, sustained elevations in HR in conjunction with deficient vagal modulation predicts risk for future cardiovascular disease. As such, the current data suggest that the presence of an anxiety disorder may identify youth who exhibit autonomic profiles that place them at risk for cardiac disease.

Effects of women's stress-elicited physiological activity and chronic anxiety on fetal heart rate.

ABSTRACT. This study examined the effects of pregnant women’s acute stress reactivity and chronic anxiety on fetal heart rate (HR). Thirty-two healthy third trimester pregnant women were instrumented to monitor continuous electrocardiography, blood pressure, respiration, and fetal HR. Subjects completed the trait anxiety subscale of the State Trait Anxiety Index, then rested quietly for a 5-minute baseline period, followed by a 5-minute Stroop color-word matching task and a 5-minute recovery period. Fetal HR changes during women’s recovery from a stressful task were associated with the women’s concurrently collected HR and blood pressure changes (r = .63, p < .05). Fetal HR changes during recovery, as well as during women’s exposure to the Stroop task, were correlated with their mothers’ trait anxiety scores (r = .39, p < .05 and r = −.52, p < .01, respectively). Finally, a combination of measures of women’s cardiovascular activity during recovery and trait anxiety scores accounted for two thirds of the variance in fetal HR changes during the same recovery period (R2 = .69, p < .001). The results from this study link changes in fetal behavior with acute changes in women’s cardiovascular activity after psychological stress and women’s anxiety status. This indicates that variations in women’s emotion-based physiological activity can affect the fetus and may be centrally important to fetal development.

Perinatal depression—The fourth inflammatory morbidity of pregnancy?: Theory and literature review

Perinatal depression is one of the leading causes of maternal morbidity and mortality. The biological etiology of this disorder remains in question, despite considerable research into the contributions of hormonal imbalance, the role of monoamines, and dysregulation of the HPA axis. Because inflammation is known to be associated with major depression in men and non-perinatal women as well as with other important morbidities of pregnancy (such as preeclampsia, preterm birth, and gestational diabetes), and because these morbidities may correlate with perinatal depression, inflammation may be a common physiological pathway that can also help explain perinatal depression. In this paper, we review the theoretical background of inflammation in perinatal depression and then review the literature concerning immune and inflammatory factors in the etiology and course of perinatal depression. We close with recommendations for future studies in this still relatively unexplored area. Identification and understanding of a common pathophysiology between other pregnancy morbidities and perinatal depression would link physical and mental well-being, likely leading to better treatment and prevention.

Practitioner Review: Maternal mood in pregnancy and child development: implications for child psychology and psychiatry

BACKGROUND The empirical base suggesting a link between prenatal maternal anxiety, stress or depression and cognitive, behavioral, and biological outcomes in the infant and child has increased dramatically in the past 10 years. METHODS In this review, we consider the relevance of prenatal maternal mood for child mental health practitioners; the empirical base for a likely causal impact of the link between prenatal anxiety, depression, or stress and child outcomes; the degree to which the available evidence is sufficient for informing or altering clinical practice; and the possible role of prenatal interventions for promoting child health and development. A selective review of PubMed, Cochrane Library and other sources was undertaken. FINDINGS Clinically significant links between maternal prenatal distress and child behavioral and cognitive outcomes have been reported; predictions to stress physiology, immunology, and neurodevelopment have been reported but the effect sizes and clinical significance is less clear. Several candidate mechanisms have been proposed, with some supporting evidence. Many behavioral treatments for prenatal maternal distress exist, but their application to promoting child health is largely unknown. CONCLUSIONS Research on maternal prenatal distress is a good example of translational research and offers a strong paradigm for promoting interdisciplinary clinical research on child health and development.

Effects of maternal breathing rate, psychiatric status, and cortisol on fetal heart rate

Womens experiences during pregnancy are predictive of variation in neurobehavioral profiles in their children. Few studies have assessed these relationships during the prenatal period. In 113 women in the 36(th) -38(th) gestational week (mean age 26.3 ± 5.4 years), electrocardiogram, blood pressure, respiration, salivary cortisol, and fetal heart rate (HR) were measured during baseline, a psychological challenge (Stroop color-word matching task), and a standardized paced breathing protocol. Subjects underwent the Structured Clinical Interview for DSM-IV prior to testing and were grouped as: depressed, co-morbid for depression and anxiety, anxiety disorder only, and control. There was a significant main effect of maternal diagnostic group on fetal HR only during the Stroop task: fetuses of women in the co-morbid group had a greater HR increase compared to controls (p < .05). Overall, fetuses showed robust increases in HR during paced breathing (p < .0001), and there was no significant difference by maternal diagnosis. For both tasks, changes in fetal HR were independent of womens concurrent cardiorespiratory activity. Finally, although cortisol was higher in the co-morbid group (p < .05), across all participants, there was a trend for maternal baseline cortisol to be positively associated with average fetal HR (p = .06). These findings indicate that variation in fetal HR reactivity-an index of emerging regulatory capacities-is likely influenced by multiple acute and chronic factors associated with womens psychobiology.

Cardiac Autonomic Control and Treatment of Hostility: A Randomized Controlled Trial

Objective: To test whether reduction in hostility increases autonomic regulation of the heart. Methods: In this randomized controlled trial, participants were 158 healthy adults, aged 20 years to 45 years, who were 1 standard deviation (SD) above national norms on the Cook-Medley Hostility and the Spielberger Trait Anger Indices. Participants also were interviewed, using the Interpersonal Hostility Assessment Technique (IHAT). They were randomly assigned to a 12-week cognitive behavior therapy program for hostility reduction or a wait-list control condition. The main outcome measure was cardiac autonomic modulation, measured as RR interval variability (RRV) derived from 24-electrocardiographic recordings. Results: In a multivariate analysis of variance assessing psychological outcomes of hostility, anger, and IHAT scores, there was a significant treatment effect with an average reduction across the three outcomes that was approximately 0.7 SD (ES = 0.685, SE = 0.184, p < .001) greater for the intervention group than for the control group. In contrast, the change in heart rate was −0.14 beat/min (95% Confidence Interval [CI] = −2.43, 2.14) in treatment participants and −1.36 beat/min (95% CI = −3.28, 0.61) in wait-list participants. High-frequency RRV, an index of cardiac parasympathetic modulation, increased by 0.07 ln ms2 (95% CI = −0.10, 0.24) for participants in the treatment condition and decreased by 0.04 ln ms2 (95% CI = −0.18, 0.10) for participants in the wait-list condition. These differences were not significant. The findings for other indices of RRV were similar. Conclusions: Reduction of hostility and anger was not accompanied by increases in cardiac autonomic modulation. These findings raise questions about the status of disordered autonomic nervous system regulation of the heart as a pathophysiological mechanism underlying the hostility-heart disease relationship and about whether hostility itself is a mechanism or merely a marker of elevated risk of heart disease. SD = standard deviation; CBT = cognitive behavior therapy; RRV = RR interval variability; ECG = electrocardiogram; HR = heart rate; HF = high frequency; ln = natural log; CI = confidence interval; ANS = autonomic nervous system; STAXI = State Trait Anger Expression Inventory; SDRR = standard deviation of normal to normal RR intervals; ES = effective size; SE = standard error; LF = low frequency; CHD = coronary heart disease.