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ABSTRACT: Thirteen percent of women experience postpartum depression. Prenatal screening for anticipated postpartum social support, a postpartum depression risk factor, may allow for early intervention. We sought to validate use of a modified version of the Postpartum Social Support Questionnaire (PSSQ) in pregnant women at increased risk for postpartum depression. Factor analysis using orthogonal varimax rotation was used. The modified PSSQ, administered during pregnancy, yields similar loading patterns as observed in postpartum administration of the original PSSQ.
Archives of Women s Mental Health 05/2012; 15(4):307-11. · 2.06 Impact Factor
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ABSTRACT: Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric illnesses commonly encountered in women during their reproductive years, including epilepsy and bipolar disorder. Despite their widespread use, the impact of prenatal exposure on fetal development remains obscure. To evaluate whether AEDs taken by pregnant mothers influence DNA methylation patterns in their neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose mothers were treated for neuropsychiatric illness during pregnancy and interrogated across 27,578 CpG sites using the Illumina HumanMethylation27 BeadChip. The association of each methylation value with the cumulative duration of prenatal AED exposure was examined using a linear mixed model. The average methylation level across all CpG sites was calculated for each subject, and this global methylation measure was evaluated similarly. Neonates with a longer duration of AED exposure in pregnancy showed a decrease in average global methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes significantly decreased with the duration of prenatal AED exposure even after adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of these neonates, a second tissue, placenta, was available in addition to cord blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in placental tissue. These novel data suggest decreased DNA methylation in neonates of mothers who took AEDs during pregnancy. The long-term stability and potential impact of these changes warrant further attention, and caution may be warranted before prescribing AEDs to pregnant women.
Epigenetics: official journal of the DNA Methylation Society 05/2012; 7(5):458-63. · 4.58 Impact Factor
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ABSTRACT: Prenatal exposure both to maternal psychiatric illness and psychiatric medication has been linked with adverse child outcomes that affect physiological, emotional and psychiatric development. Studies suggest that epigenetic mechanisms, such as DNA methylation, may facilitate these effects. In this report, we explore the association between maternal psychiatric illness and treatment during pregnancy and neonatal DNA methylation patterns in a prospectively-characterized clinical cohort of 201 dyads. Associations between the percent of umbilical cord blood DNA methylated at 27,578 CpG sites and maternal psychiatric diagnosis, symptoms and antidepressant use were evaluated by fitting a separate linear mixed effects model for each CpG site. There were no significant changes in neonatal DNA methylation attributable to maternal psychiatric diagnosis or depressive symptoms during pregnancy. Exposure to an antidepressant medication was associated with differential methylation of CpG sites in TNFRSF21 and CHRNA2 (false discovery rate < 0.05), but the average difference in methylation for both CpG sites was less than 3% between each group. The results were not specific to type of antidepressant or duration of the exposure. This study suggests that there are no large effects of maternal psychiatric illness, depressive symptoms or prenatal exposure to antidepressants on neonatal DNA methylation. Delineation of the influence of maternal psychiatric illness and pharmacological exposures on the developing fetuses has critical implications for clinical care during pregnancy.
Epigenetics: official journal of the DNA Methylation Society 04/2012; 7(4):409-14. · 4.58 Impact Factor
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ABSTRACT: Because bipolar disorder can be difficult to diagnose, we compared characteristics of women with confirmed versus presumably misdiagnosed bipolar disorder.
This cohort study was conducted from July 2005 to January 2010 in the outpatient clinic of the Emory Women's Mental Health Program, Atlanta, Georgia. Young adult women (mean age = 32 years) who were either pregnant or planning to conceive and who reported having previous clinical diagnoses of bipolar disorder completed 2 independent diagnostic assessments: the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and an evaluation by a perinatal mood-disorder expert who was masked to the SCID findings. We compared clinical characteristics of women with confirmed versus presumably misdiagnosed bipolar disorder by bivariate testing followed by multivariate logistic regression modeling.
Of 199 participants, 141 (70.9%) had confirmed DSM-IV bipolar disorder on the basis of concordant assessments, 23 (11.6%) were considered misdiagnosed, and 35 (17.6%) who had discordant diagnostic assessments were excluded from further analysis. Multivariate modeling indicated that confirmed bipolar disorder was associated with a history of antidepressant-associated mania/hypomania (OR = 13.30; 95% CI, 3.32-53.20; P = .0003), psychotic symptoms (OR = 12.40; 95% CI, 2.14-71.10; P = .005), and sustained euthymia during mood-stabilizer treatment (OR = 4.53; 95% CI, 1.32-15.60; P = .02); presumably misdiagnosed bipolar disorder was associated with childhood physical abuse (OR = 8.73; 95% CI, 2.33-32.70; P = .001) and comorbid obsessive-compulsive disorder (OR = 7.26; 95% CI, 1.86-28.30; P = .004).
Several clinical factors found to distinguish women with confirmed versus presumably misdiagnosed bipolar disorder may help to refine clinical diagnosis.
The Journal of Clinical Psychiatry 02/2012; 73(2):242-6. · 5.80 Impact Factor
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James W Schroeder,
Karen N Conneely,
Joseph C Cubells,
Varun Kilaru,
D Jeffrey Newport, Bettina T Knight,
Zachary N Stowe,
Patricia A Brennan,
Julia Krushkal,
Frances A Tylavsky,
Robert N Taylor,
Ronald M Adkins,
Alicia K Smith
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ABSTRACT: Risk for adverse neonatal outcome increases with declining gestational age (GA), and changes in DNA methylation may contribute to the relationship between GA and adverse health outcomes in offspring. To test this hypothesis, we evaluated the association between GA and more than 27,000 CpG sites in neonatal DNA extracted from umbilical cord blood from two prospectively-characterized cohorts: (1) a discovery cohort consisting of 259 neonates from women with a history of neuropsychiatric disorders and (2) a replication cohort consisting of 194 neonates of uncomplicated mothers. GA was determined by obstetrician report and maternal last menstrual period. The associations between proportion of DNA methylated and GA were evaluated by fitting a separate linear mixed effects model for each CpG site, adjusting for relevant covariates including neonatal sex, race, parity, birth weight percentile and chip effects. CpG sites in 39 genes were associated with GA (false discovery rate < 0.05) in the discovery cohort. The same CpG sites in 25 of these genes replicated in the replication cohort, with each association replicating in the same direction. Notably, these CpG sites were located in genes previously implicated in labor and delivery (e.g., AVP, OXT, CRHBP and ESR1) or that may influence the risk for adverse health outcomes later in life (e.g., DUOX2, TMEM176A and CASP8). All associations were independent of method of delivery or induction of labor. These results suggest neonatal DNA methylation varies with GA even in term deliveries. The potential contribution of these changes to clinically significant postnatal outcomes warrants further investigation.
Epigenetics: official journal of the DNA Methylation Society 12/2011; 6(12):1498-504. · 4.58 Impact Factor
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ABSTRACT: To examine the association between severity of maternal depression and anxiety during pregnancy and the maternal use of medicinal agents and habit-forming substances.
Participants in a prospective study of prenatal DSM-IV depressive and anxiety disorders at the Emory Women's Mental Health Program who completed weekly documentation of prenatal drug exposure and ≥ 3 administrations of the Hamilton Depression Rating Scale (HDRS) or Hamilton Anxiety Rating Scale (HARS) were included. The primary outcome measures were the HDRS and HARS. Correlation coefficients were computed for cumulative drug exposure with HDRS area under the curve (AUC) and HARS AUC. Data collection was completed between January 2007 and June 2010.
Among 195 participants, both HDRS AUC and HARS AUC were negatively correlated with prenatal vitamin exposure (r = -0.22 [P = .002] and r = -0.26 [P = .0003], respectively) and positively correlated with tobacco (r = 0.21 [P = .003] and r = 0.20 [P = .006], respectively) and hypnotic (r = 0.28 [P < .0001] and r = 0.19 [P = .008], respectively) exposure. Only HDRS AUC correlated with exposure to antiemetics (r = 0.14 [P = .05]), opioid analgesics (r = 0.14 [P = .05]), and all prescription drugs (r = 0.16 [P = .02]). Only HARS AUC correlated with benzodiazepine exposure (r = 0.17 [P = .02]).
Both prenatal depression and anxiety are associated with decreased prenatal vitamin compliance and increased use of hypnotics and tobacco, but only depression is associated with exposure to a broader array of medications targeting physical symptoms that often accompany depression. These findings confirm and extend previous studies, underscoring the importance of addressing prenatal depression and anxiety.
The Journal of Clinical Psychiatry 11/2011; 73(2):247-51. · 5.80 Impact Factor
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ABSTRACT: Patients with epilepsy are at high risk for major depressive disorder (MDD) and, according to one report, postpartum depression (PPD) as well. The study described here sought to determine the prevalence and risk factors for PPD among women with epilepsy. Fifty-six women with epilepsy participating in a prospective study of perinatal antiepileptic drug (AED) pharmacokinetics were included. Participants completed the Beck Depression Inventory (BDI) during pregnancy and the postpartum period. Fourteen participants (25.0%) had a postnatal BDI score > or =12 indicative of PPD. Logistic regression indicated that significant risk factors for PPD among women with epilepsy included multiparity (odds ratio=12.5) and AED polytherapy (odds ratio=9.3). The rate of PPD was unaffected by the use of specific AEDs. In conclusion, PPD rates are higher among women with epilepsy than the general population, particularly those who are multiparous or receiving AED polytherapy, and there is no evidence that AED selection modifies this risk.
Epilepsy & Behavior 11/2009; 16(3):426-30. · 2.34 Impact Factor
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ABSTRACT: Cytokines of the innate immune response may contribute to behavioral alterations that resemble major depression as manifested in medically healthy individuals.
To explore potential similarities and differences between cytokine-induced depression and idiopathic major depression in healthy subjects, dimensional analyses comparing specific symptom dimensions of depression were conducted in 20 patients with malignant melanoma administered the innate immune cytokine, interferon (IFN)-alpha, and 28 medically healthy subjects with major depression of similar age and gender distribution. The Hamilton Rating Scale for Depression was used to assess severity of individual depressive symptoms.
Severity of symptoms of anxiety, depressed mood, and impaired work/activities were comparable between patients with IFN-alpha-induced depression and medically healthy depressed patients. Interestingly, however, compared to medically healthy patients with major depression, patients with IFN-alpha-induced depression reported significantly greater psychomotor retardation and weight loss and significantly less severe feelings of guilt.
The relatively small sample size limited statistical power to detect small differences in symptom expression among groups.
The data suggest that there is considerable overlap in symptom expression between cytokine-induced depression and idiopathic depression in medically healthy subjects. Nevertheless, differences in isolated symptom domains suggest that cytokines may preferentially target neurocircuits relevant to psychomotor activity (e.g. basal ganglia), while having a limited effect on cognitive distortions regarding self-appraisal.
Journal of affective disorders 04/2009; 119(1-3):181-5. · 3.76 Impact Factor
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D Jeffrey Newport,
Martha R Calamaras,
C Lindsay DeVane,
Jennifer Donovan,
Aquila J Beach,
Stephanie Winn, Bettina T Knight,
Bryan B Gibson,
Adele C Viguera,
Michael J Owens,
Charles B Nemeroff,
Zachary N Stowe
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ABSTRACT: There are limited data regarding the use of atypical antipsychotic medications in pregnancy. The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery.
The authors conducted a prospective observational study of women treated with an atypical antipsychotic or haloperidol during pregnancy. Maternal and umbilical cord plasma samples collected at delivery were analyzed for medication concentrations. Placental passage was defined as the ratio of umbilical cord to maternal plasma concentrations (ng/ml). Obstetrical outcome was ascertained through maternal reports and reviews of obstetrical records.
Fifty-four pregnant women with laboratory-confirmed antipsychotic use proximate to delivery were included in the analysis. Complete maternal-infant sample pairs were available for 50 participants. Placental passage ratio was highest for olanzapine (mean=72.1%, SD=42.0%), followed by haloperidol (mean=65.5%, SD=40.3%), risperidone (mean=49.2%, SD=33.9%), and quetiapine (mean=23.8%, SD=11.0%). There were tendencies toward higher rates of low birth weight (30.8%) and neonatal intensive care unit admission (30.8%) among neonates exposed to olanzapine.
All four antipsychotics demonstrated incomplete placental passage. Quetiapine demonstrated the lowest placental passage of the medications studied. These novel data provide an initial quantification of the placental passage of antipsychotics and fetal exposure in humans, demonstrating significant differences between individual medications.
American Journal of Psychiatry 09/2007; 164(8):1214-20. · 12.54 Impact Factor
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ABSTRACT: Tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor was evaluated for the treatment of patients with social anxiety disorder (SAD). Adults with SAD received open-label tiagabine 4-16 mg per day for 12 weeks. Intent-to-treat data are available for 54 patients with improvement demonstrated in Liebowitz Social Anxiety Scale, Clinician Global Impression-Severity (CGI-S) and -Improvement (CGI-I), Social Phobia Inventory, and Sheehan Disability Scale scores. In all, 40.7% (22/54) of the intent to treat sample and 63.0% (17/27) of the completer sample were considered CGI responders (CGI-I score of one or two). Tiagabine was generally well tolerated. Results of this pilot study suggest that tiagabine may be an option for the treatment of patients with SAD. Larger, controlled studies are required to fully elucidate the potential of tiagabine for the treatment of SAD.
Human Psychopharmacology Clinical and Experimental 07/2007; 22(4):241-4. · 2.48 Impact Factor
