Childhood maltreatment exposure is differentially associated with transdiagnostic perinatal depression symptoms.

History of childhood maltreatment (CM) is common and robustly associated with prenatal and postpartum (perinatal) depression. Given perinatal depression symptom heterogeneity, a transdiagnostic approach to measurement could enhance understanding of patterns between CM and perinatal depression. METHODS: In two independently collected samples of women receiving care at perinatal psychiatry clinics (n = 523 and n = 134), we categorized longitudinal symptoms of perinatal depression, anxiety, stress, and sleep into transdiagnostic factors derived from the Research Domain Criteria and depression literatures. We split the perinatal period into four time points. We conducted a latent profile analysis of transdiagnostic factors in each period. We then used self-reported history of CM (total exposure and subtypes of abuse and neglect) to predict class membership. RESULTS: A three-class solution best fit our data. In relation to positive adaptive functioning, one class had relatively more positive symptoms (high adaptive), one class had average values (middle adaptive), and one class had fewer adaptive symptoms (low adaptive). More total CM and specific subtypes associated with threat/abuse increased an individual's likelihood of being in the Low Adaptive class in both samples (ORs: 0.90-0.97, p < .05). LIMITATIONS: Generalizability of our results was curtailed by 1) limited racial/ethnic diversity and 2) missing data. CONCLUSIONS: Our results support taking a person-centered approach to characterize the relationship between perinatal depression and childhood maltreatment. Given evidence that increased exposure to childhood maltreatment is associated with worse overall symptoms, providers should consider incorporating preventative, transdiagnostic interventions for perinatal distress in individuals with a history of childhood maltreatment.

Associations between mothers' and fathers' depression and anxiety prior to birth and infant temperament trajectories over the first year of life: Evidence from diagnoses and symptom severity.

BACKGROUND: Developmental shifts in infant temperament predict distal outcomes including emerging symptoms of psychopathology in childhood. Thus, it is critical to gain insight into factors that shape these developmental shifts. Although parental depression and anxiety represent strong predictors of infant temperament in cross-sectional research, few studies have examined how these factors influence temperament trajectories across infancy. METHODS: We used latent growth curve modeling to examine whether mothers' and fathers' anxiety and depression, measured in two ways - as diagnostic status and symptom severity - serve as unique predictors of developmental shifts in infant temperament from 3 to 12 months. Participants included mothers (N = 234) and a subset of fathers (N = 142). Prior to or during pregnancy, both parents were assessed for lifetime diagnoses of depression and anxiety as well as current severity levels. Mothers rated their infants' temperament at 3, 6, and 12 months of age. RESULTS: Mothers' depression and anxiety primarily predicted initial levels of temperament at 3 months. Controlling for mothers' symptoms, fathers' depression and anxiety largely related to temperament trajectories across infancy. Lifetime diagnoses and symptom severities were associated with distinct patterns. LIMITATIONS: Infant temperament was assessed using a parent-report measure. Including an observational measure would provide a more comprehensive picture of the infants' functioning. CONCLUSIONS: These results indicate that mothers' and fathers' mental health are uniquely associated with infant temperament development when measured using diagnostic status and/or symptom severity. Future studies should examine whether these temperament trajectories mediate intergenerational transmission of risk for depression and anxiety.

Positive affect improves a transdiagnostic model of perinatal depression symptoms.

INTRODUCTION: Accurate measurement of perinatal depression is vital. We aimed to 1) test whether a factor that measured positive affect (PA) bettered a transdiagnostic model of depression symptoms and 2) replicate the model in a second sample. METHODS: We conducted secondary analyses from two samples (n's = 657 and 142) of women in treatment at perinatal psychiatric clinics. Data were derived from items from seven commonly used measures. We compared fit indices from our original factor model-one general and six specific factors derived from the Research Domain Criteria (Loss, Potential Threat, Frustrative Nonreward, and Sleep-Wakefulness) and depression literatures (Somatic and Coping)-to our novel factor model with a PA factor. The PA factor was created by recategorizing items that measured affective states with a positive valence into a new factor. Sample 1 data were split into six perinatal periods. RESULTS: In both samples, the addition of a PA factor improved model fit. At least partial metric invariance was found between perinatal periods, with the exception of trimester 3 - postpartum period 1. LIMITATIONS: Our measures did not operationalize PA in the same way as in the positive valence system in RDoC and we were unable to perform longitudinal analyses on our cross-validation sample. CONCLUSIONS: Clinicians and researchers are encouraged to consider these findings as a template for understanding symptoms of depression in perinatal patients, which can be used to guide treatment planning and the development of more effective screening, prevention, and intervention tools to prevent deleterious outcomes.

Pregnant women with bipolar disorder who have a history of childhood maltreatment: Intergenerational effects of trauma on fetal neurodevelopment and birth outcomes.

OBJECTIVES: Intergenerational transmission of trauma occurs when the effects of childhood maltreatment (CM) influence the next generation's development and health; prenatal programming via maternal mood symptoms is a potential pathway. CM is a risk factor for bipolar disorder which is present in 1.8% of pregnant women. Mood symptoms are likely to increase during pregnancy, particularly for those with a history of CM. We examined whether there was evidence for intergenerational transmission of trauma in utero in this population, and whether maternal mood was a transmission pathway. METHODS: CM and maternal mood were self-reported by N = 82 pregnant women in treatment for bipolar disorder. Fetal heart rate variability (FHRV) was measured at 24, 30, and 36 weeks' gestation. Gestational age at birth and birth weight were obtained from medical charts. RESULTS: A cluster analysis yielded two groups, Symptom+ (18.29%) and Euthymic (81.71%), who differed on severe mood symptoms (p < 0.001) but not on medication use. The Symptom+ group had more CM exposures (p < 0.001), a trend of lower FHRV (p = 0.077), and greater birth complications (33.3% vs. 6.07% born preterm p < 0.01). Maternal prenatal mood mediated the association between maternal CM and birth weight in both sexes and at trend level for gestational age at birth in females. CONCLUSIONS: This is the first study to identify intergenerational effects of maternal CM prior to postnatal influences in a sample of pregnant women with bipolar disorder. These findings underscore the potential enduring impact of CM for women with severe psychiatric illness and their children.

The severity and role of somatic depressive symptoms in psychological networks in a longitudinal sample of peripartum women.

The inclusion of somatic symptoms in assessing peripartum depression (PPD), which encompasses depression during pregnancy and the postpartum period, has remained controversial, as there is substantial overlap between somatic depression symptoms and normal features of pregnancy/postpartum. This study examined whether trajectories differed by PPD symptom subscale and whether PPD symptom networks changed as a function of the peripartum phase. 418 women with a history of neuropsychiatric illness participated in a longitudinal observational study, completing symptom questionnaires assessing affective, cognitive, and somatic symptoms throughout pregnancy and the first year postpartum. Assessments were grouped into five peripartum phases: three trimesters of pregnancy and early/late postpartum. Two analyses were performed. First, a series of multilevel spline regression models examined depression subscale trajectories over peripartum phase. Second, symptom networks and related metrics were estimated for each peripartum phase and compared. Somatic symptoms were most severe and had the most variable peripartum trajectory. The role of somatic symptoms within the networks also changed as a function of peripartum phase. Our results suggest that somatic symptoms can be severe and may play a crucial role in the maintenance of PPD. Thus, somatic symptoms should not be disregarded when assessing for PPD in obstetrical, psychiatric, and pediatric clinics, and clinical research.

Buprenorphine Medication for Opioid Use Disorder: A Study of Factors Associated With Postpartum Treatment Retention.

BACKGROUND AND OBJECTIVES: The factors associated with medication for opioid use disorder (MOUD) treatment retention among pregnant women with opioid use disorder (OUD) are largely unknown. This study sought to characterize factors associated with postpartum treatment retention. METHODS: A retrospective chart review from 2014 to 2017 was conducted among women with OUD in pregnancy treated with buprenorphine. Women were assigned to the treatment retention group if they attended an appointment within 10 to 14 weeks postpartum. Others were assigned to the dropout group. The groups were compared using bivariate analysis for sociodemographic variables, obstetrical and neonatal outcomes, clinical and subjective opioid withdrawal symptoms, buprenorphine dosage, urine drug toxicology (UDT) results, and other factors. RESULTS: A total of 64 pregnancies received treatment until delivery, and 47 (73.1%) were retained in treatment by 12 weeks postpartum. The treatment dropout group had lower buprenorphine doses at delivery, a higher percentage of benzodiazepine positive UDT, and number of UDT positive for benzodiazepine in the third trimester. Breastfeeding rates were higher in the treatment retention group. DISCUSSION AND CONCLUSIONS: Future research of variables related to postpartum treatment retention is needed to provide guidelines regarding MOUD during the perinatal period and to optimize maternal and fetal well-being. SCIENTIFIC SIGNIFICANCE: This study supports previous recommendations that aggressive treatment of withdrawal symptoms in pregnant women with OUD is needed to maximize treatment retention. This is the first study to find that breastfeeding was associated with postpartum treatment retention; while, increased use of benzodiazepines during pregnancy was associated with postpartum treatment dropout. (Am J Addict 2021;30:43-48).

Drug screening during pregnancy: Urine dip cups measure up.

BACKGROUND: Substance use during pregnancy is a major medical and public health concern. Determination of the most appropriate screening protocol remains a clinical conundrum. Interviews and/or laboratory drug screens may be costly, inaccurate, and are frequently inadequate to identify patterns of substance use for a given population or geographic area. We compared commercially available urine "dip cup" toxicology screens obtained in the clinic to university hospital drug toxicology results. METHODS: 267 observed urine samples were collected from pregnant women with known substance use disorders enrolled in a specialized treatment program that included access to buprenorphine medication-assisted treatment. Each urine sample was tested by commercial dip cup with temperature confirmation and then sent to the university hospital laboratory for analyses. The number of substances detected and cost for each screening method were compared. RESULTS: Uniformly, the dip cup had comparable detection of amphetamines, barbiturates, cocaine, methadone, opiates, and tetrahydrocannabinol to the university hospital laboratory with the exception of benzodiazepines. In addition, the dip cup detected use of buprenorphine (a commonly misused opiate receptor ligand not included in the hospital screen) and was significantly less expensive. CONCLUSIONS: Commercially available urine dip cups are cost-effective, equally comparable to hospital based screening, and provide 'real time' results germane to clinical care and treatment planning.

Patterns of Positivity: Positive Affect Trajectories Among Infants of Mothers with a History of Depression.

This study examined positive affect (PA) trajectories over the first year of life among infants of mothers with a history of depression (N = 191) as well as predictors (i.e., maternal prenatal and postpartum depression symptoms, maternal parenting behaviors) of those trajectories. Infant PA was observed in play and feeding tasks during lab visits at 3, 6, and 12 months of age; parenting behaviors were observed at 3 months. Mothers completed questionnaires regarding their symptoms of depression throughout the prenatal period and during the first 3 months postpartum. Growth curve analyses indicated that infant PA increased across time, and this finding replicated across both the play and feeding tasks, though increases slowed over time. Neither maternal prenatal nor postpartum depression symptoms predicted infants' PA trajectories, but mothers' PA, positive parenting, and disengaged parenting were associated with infant PA during the play task. Our finding that infant PA increased over the first year postpartum suggests PA trajectories among infants of mothers with a history of depression may be indices of resilience, despite risks associated with their mothers' history of depression. Furthermore, this study highlights parenting behaviors that may be important targets of prevention and early intervention efforts to bolster infant PA.

Buprenorphine medication-assisted treatment during pregnancy: An exploratory factor analysis associated with adherence.

BACKGROUND: The treatment of pregnant women with opioid use disorder is challenging due to the myriad of physical, mental, and social complications. Factors influencing adherence to buprenorphine during pregnancy have not been identified. MATERIALS AND METHODS: Pregnant women with opioid use disorder followed in a tertiary clinic were included in a retrospective chart review from buprenorphine induction through delivery. All women who had been evaluated and treated with buprenorphine from January 1, 2014, to September 31, 2016, were included. Adherence was defined as follows: 1) adherent: attended follow up visits, negative urine toxicology screens, and phase advancement; 2) moderately adherent: attended follow up visits until delivery, had not completed six negative urine toxicology screens, or had positive urine toxicology screens (i.e., no phase advancement); 3) non-adherent: missed follow up visits and did not stay in treatment until delivery. Sociodemographic characteristics, family psychiatric history, current and lifetime psychiatric and childhood trauma along with treatment factors were compared by category of adherence. RESULTS: 64 women met criteria for inclusion in this study with 41 (64%) adherent; eight (13%) moderately adherent; and 15 (23%) non-adherent. In the non-adherent group compared to the adherent group, the clinician-rated opioid withdrawal scale score was significantly higher, and the daily buprenorphine dose at last visit was significantly lower. CONCLUSIONS: Women who were non-adherent to buprenorphine during pregnancy had higher severity of opioid withdrawal symptoms and lower doses of buprenorphine. These findings should be further explored with the goal of optimizing care without increasing risk for neonates.

Major depressive disorder during pregnancy: Psychiatric medications have minimal effects on the fetus and infant yet development is compromised.

Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85-114) with rates of delay more than 2-3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother-infant dyads.

Course of ante- and postnatal depressive symptoms related to mothers' HPA axis regulation.

Given high health costs of depression during pregnancy and the first postnatal year, it is important to understand mechanisms involved in the emergence and perpetuation of symptoms during this time. In a series of 2 studies, we aim to clarify bidirectional relations between mothers' physiological stress regulation-stress-related activation of the hypothalamic-pituitary-adrenal (HPA) axis-and their course of depressive symptoms. In Study 1, 230 pregnant women recruited from a women's mental health program gave 3 saliva samples in the context of psychosocial stress at 24, 30, and 36-weeks gestation. They self-reported depressive symptoms across the three trimesters of pregnancy and first year postpartum. Multilevel models revealed women with elevated salivary cortisol during pregnancy showed a course of escalating ante- and postnatal symptoms, implicating HPA hyperactivation as a precursor to worsening mood problems. In Study 2, 54 mothers from a community sample self-reported depressive symptoms at 3, 6, 12, and 18 months postnatal. At 18 months, they participated in a dyadic stress task with their infant and gave 4 saliva samples for cortisol assay. For mothers with a lifetime depression diagnosis, an escalating course of postnatal symptoms predicted a higher, flatter cortisol response profile. Together, the results of these studies suggest that for high-risk mothers, a trajectory of worsening depression may both follow from and give rise to neuroendocrine stress hyperactivation. These findings suggest greater attention is warranted to course of depressive symptoms across the ante- and postnatal period, rather than symptom levels at any given time, to characterize health risks. (PsycINFO Database Record

An exploratory study of whether pregnancy outcomes influence maternal self-reported history of child maltreatment.

Childhood maltreatment is common and has been increasingly studied in relation to perinatal outcomes. While retrospective self-report is convenient to use in studies assessing the impact of maltreatment on perinatal outcomes, it may be vulnerable to bias. We assessed bias in reporting of maltreatment with respect to women's experiences of adverse perinatal outcomes in a cohort of 230 women enrolled in studies of maternal mental illness. Each woman provided a self-reported history of childhood maltreatment via the Childhood Trauma Questionnaire at two time points: 1) the preconception or prenatal period and 2) the postpartum period. While most women's reports of maltreatment agreed, there was less agreement for physical neglect among women experiencing adverse perinatal outcomes. Further, among women who discrepantly reported maltreatment, those experiencing adverse pregnancy outcomes tended to report physical neglect after delivery but not before, and associations between physical neglect measured after delivery and adverse pregnancy outcomes were larger than associations that assessed physical neglect before delivery. There were larger associations between post-delivery measured maltreatment and perinatal outcomes among women who had not previously been pregnant and in those with higher postpartum depressive symptoms. Although additional larger studies in the general population are necessary to replicate these findings, they suggest retrospective reporting of childhood maltreatment, namely physical neglect, may be prone to systematic differential recall bias with respect to perinatal outcomes. Measures of childhood maltreatment reported before delivery may be needed to validly estimate associations between maternal exposure to childhood physical neglect and perinatal outcomes.

Rating scale item assessment of self-harm in postpartum women: a cross-sectional analysis.

We examined the utility of screening instruments to identify risk factors for suicidal ideation (SI) in a population of women with neuropsychiatric illnesses at high risk for postpartum depression. Pregnant women with neuropsychiatric illness enrolled prior to 20 weeks of gestation. Follow-up visits at 4-8-week intervals through 13 weeks postpartum included assessment of depressive symptoms with both clinician and self-rated scales. A total of 842 women were included in the study. Up to 22.3% of postpartum women admitted SI on rating scales, despite the majority (79%) receiving active pharmacological treatment for psychiatric illness. Postpartum women admitting self-harm/SI were more likely to meet criteria for current major depressive episode (MDE), less than college education, an unplanned pregnancy, a history of past suicide attempt, and a higher score on the Childhood Trauma Questionnaire. In women with a history of neuropsychiatric illness, over 20% admitted SI during the postpartum period despite ongoing psychiatric treatment. Patient-rated depression scales are more sensitive screening tools than a clinician-rated depression scale for +SI in the postpartum period.

Prospective Longitudinal Study of Predictors of Postpartum-Onset Depression in Women With a History of Major Depressive Disorder.

OBJECTIVE: Risk factors for postpartum depression in euthymic pregnant women with histories of major depressive disorder (MDD) were evaluated. METHODS: From April 2003 to March 2009, 343 pregnant women with a history of Structured Clinical Interview for DSM-IV (SCID)-diagnosed major depressive disorder were prospectively assessed from the third trimester into the postpartum period using the SCID mood module and 17-item Hamilton Depression Rating Scale (HDRS). Data from 300 subjects who completed at least 2 mood module assessments (1 within 60 days before and the other within 60 days after delivery) were analyzed for predictive associations between variables assessed in the third trimester and the development of a postpartum depression. RESULTS: The majority of women were euthymic in pregnancy by SCID criteria. Women with third trimester SCID-diagnosed depression (n = 45) versus euthymia (n = 255) had a significantly higher risk for having depression after delivery (24% vs 11%, P = .013). For pregnant euthymic women, third trimester total HDRS scores significantly predicted postpartum depression (P < .0001); specifically, scores on 3 HDRS items alone-work activities, early insomnia, and suicidality-significantly predicted postpartum depression. Antidepressant use in the third trimester in euthymic women did not confer protection against the onset of postpartum depression. CONCLUSIONS: Among women with a history of MDD who are euthymic in the third trimester, 3 HDRS items-work activities, early insomnia, and suicidality-may be useful as screening items for clinicians working with pregnant women with histories of MDD to identify a group at risk for developing postpartum depression. Additionally, in euthymic women with a history of MDD, antidepressant use in the third trimester may not reduce the risk of developing postpartum depression.

Prenatal Psychostimulant and Antidepressant Exposure and Risk of Hypertensive Disorders of Pregnancy.

OBJECTIVE: To investigate the association, if any, of prenatal mental illness and psychotropic exposure with the risk of hypertensive disorders of pregnancy (HDP). METHODS: A case-cohort analysis was conducted of 686 pregnant women participating in prospective, longitudinal observational studies in a tertiary referral center between January 1998 and May 2012. Risk estimates were produced using multivariate logistic regression modeling. Medication- and diagnosis-specific data were utilized to conduct post hoc confirmatory analyses of the risk estimates. RESULTS: After adjustment for confounders, HDP were significantly associated with psychostimulant (odds ratio [OR] = 6.11; 95% CI, 1.79-20.9) and serotonin-norepinephrine reuptake inhibitor (SNRI) (OR = 2.57; 95%, 1.34-4.93) exposure following the 20th week of gestation and lifetime histories of cocaine dependence (OR = 2.99; 95% CI, 1.12-7.98) and panic disorder (OR = 1.78; 95% CI, 1.06-2.98) using DSM-IV diagnostic criteria. HDP risk was not associated with prenatal selective serotonin reuptake inhibitor exposure or other psychiatric disorders. Post hoc analyses demonstrated an increased risk for HDP with higher maternal daily doses of amphetamine psychostimulants and the SNRI venlafaxine. CONCLUSIONS: These data indicate that psychostimulant and SNRI exposure following the 20th week of gestation conveys considerable risk for the emergence of HDP. Overall, the findings suggest that heightened vascular reactivity to noradrenergic, rather than serotonergic, stimulation may be pivotal to HDP risk among women with psychiatric illness.

Test-retest reliability of retrospective self-reported maternal exposure to childhood abuse and neglect.

Retrospective reports of exposure to childhood trauma indicate it is common. There is growing interest in relationships between maternal exposure to childhood adversity, perinatal mental health, and pregnancy outcomes. The goal of this study was to describe the self-reported prevalence and test-retest reliability of exposure to childhood maltreatment using the Childhood Trauma Questionnaire among adult women around the time of pregnancy. A substantial proportion of women reported exposure to maltreatment and reliability was generally at least moderate, indicating consistent reporting.

Obsessive-compulsive disorder in pregnancy and the postpartum period: course of illness and obstetrical outcome.

The study aimed to examine the course of obsessive-compulsive disorder (OCD) across pregnancy and its impact on obstetric and neonatal outcomes. Women enrolled prior to 20-week gestation in a prospective, observational study. The Structured Clinical Interview for DSM-IV was completed to obtain lifetime Axis I diagnoses. A total of 56 women with OCD were followed at 1 to 3-month intervals through 52 weeks postpartum. Each visit, the Yale-Brown Obsessive Compulsive Scale (YBOCS), clinical assessment, and medication/exposure tracking were performed. Obstetric and neonatal data were abstracted from the medical record. In subjects with OCD, associations between perinatal obsessive-compulsive symptoms (OCSs) and outcomes were examined. Additionally, outcomes were compared to 156 matched psychiatric patients without OCD. Maternal age inversely correlated with the YBOCS scores across the study period (ß = -0.5161, p = .0378). Cesarean section was associated with increased OCSs in the postpartum period compared to vaginal delivery (ß = 5.3632, p = 0.043). No associations were found between severity of perinatal obsessions or compulsions and any specific obstetric or neonatal complications. Subjects without OCD had higher frequency of fetal loss compared to mothers with OCD (χ (2) = 4.03, p = 0.043). These novel prospective data fail to identify an association of OCSs with adverse outcomes. In contrast, there is an association of delivery method and younger maternal age with increased postnatal symptoms of OCD. Psychiatric subjects without OCD may have a higher risk of miscarriage and intrauterine fetal demise compared to subjects with OCD.

Temperament and behavior in toddlers of mothers with bipolar disorder: a preliminary investigation of a population at high familial risk for psychopathology.

OBJECTIVE: There are no published studies examining concurrent associations between temperament and behavior during toddlerhood in offspring of parents with bipolar disorder (OBD), a population at high familial risk for psychopathology. Better understanding of early determinants contributing to well-being or mental illness in this high-risk population has the potential to aid in the identification of problem domains to be targeted clinically, and facilitate the development of early intervention and prevention initiatives for an appropriate subgroup of children at the youngest possible age. METHODS: A total of 30 offspring of mothers with BD (mean age=25.4±4.9 months) participated in this study at Emory University. The mothers completed the Early Childhood Behavior Questionnaire (ECBQ) and the Child Behavior Checklist (CBCL). RESULTS: The results of the correlational analyses indicated that the broad temperament dimension Negative Affectivity and the individual ECBQ scales Sadness and Shyness were positively associated with the broad CBCL dimension Internalizing Problems, whereas Sociability was negatively associated with Internalizing Problems. In addition, the temperament scales Soothability and Frustration were negatively and positively associated with Internalizing Problems, respectively. All ECBQ scales included in the broad temperament dimension Effortful Control, except for Cuddliness, were significantly negatively associated with the broad CBCL dimension Externalizing Problems. A significant sex difference was found for the ECBQ scale Positive Anticipation and the CBCL scale Sleep Problems, with a higher mean rank score for girls than for boys. CONCLUSIONS: This is the first systematic investigation of temperament and behavior and concurrent associations between these two domains in toddlers of mothers with BD. The present findings provide a platform for future investigations of the contribution of temperament and early behavior to potential well-being or mental illness in OBD.

Carbamazepine clearance and seizure stability during pregnancy.

The aims of this study were to characterize the alterations in total and free carbamazepine (CBZ) and in total and free carbamazepine-epoxide (CBZ-EPO) clearances during pregnancy, to calculate the change in free fractions of CBZ and CBZ-EPO during pregnancy, and to determine whether seizure worsening is associated with a low ratio to nonpregnant baseline concentration of total or free CBZ or CBZ-EPO. Women on CBZ were enrolled before conception or during pregnancy in this prospective, observational study. Concomitant medications and seizure frequency were recorded. Serum total and free CBZ and CBZ-EPO were collected at each visit. Changes in the clearance of all four compounds and free fractions of CBZ and CBZ-EPO were compared with nonpregnant baseline. During pregnancy, the ratios to baseline concentrations of total and free CBZ and CBZ-EPO were compared for months with and without increased seizure frequency. Total and free CBZ and CBZ-EPO clearances were calculated in 15 pregnancies in 12 women. Clearances did not change for any of these compounds during pregnancy. The free fraction of CBZ increased from 0.23 at baseline to a maximum of 0.32 in the third trimester (p=0.008). In the six women on CBZ monotherapy with adequate seizure diaries and blood sampling, seizure worsening did not correspond to a ratio to baseline concentration of less than 0.65 for total or free CBZ or CBZ-EPO. In conclusion, total and free CBZ and CBZ-EPO clearances did not change substantially during pregnancy, and seizure frequency worsening was not associated with decreased concentrations of total or free CBZ; therefore, therapeutic drug monitoring may not be necessary for all women on CBZ during pregnancy. Further studies with larger sample sizes are needed before definitive recommendations can be made. Carbamazepine monotherapy may be a relatively safe and cost effective treatment option for women with focal epilepsy syndromes during pregnancy.

Uterine blood flow in a psychiatric population: impact of maternal depression, anxiety, and psychotropic medication.

BACKGROUND: Accumulating evidence suggests that fetal exposure to maternal psychiatric symptoms is associated with future risk for psychopathology. One potential pathway is distress-linked constriction in uterine or umbilical blood flow (UBF). With approximately 6.6% of pregnant women taking an antidepressant, an ecologically valid investigation of this hypothesis must consider the potential concomitant influence of pharmacotherapy on UBF. METHODS: Pregnant women (n = 101) with lifetime histories of mental illness were evaluated every 4 to 6 weeks during gestation for mood symptoms and medication use; women underwent an ultrasound examination for UBF at approximately 25 weeks gestation. RESULTS: No associations were observed between UBF and three assessments of maternal prenatal depression and anxiety (acute: coincident with the UBF scan; proximal: within 2 weeks of the scan; chronic: serial symptom ratings). Chronic and acute use of bupropion was associated with reduced UBF, even after controlling for pregnancy complications. Chronic use of atypical antipsychotics also was associated with decreased UBF. There were no associations between serotonergic antidepressant use and UBF. CONCLUSIONS: Contrary to a popular hypothesis, depression and anxiety-associated reductions in UBF may not be a pathway by which risk is conferred during prenatal development. However, while requiring replication, our findings suggest that prenatal bupropion exposure may be associated with reductions in UBF.