Mood symptoms in pregnant and postpartum women with bipolar disorder: a naturalistic study.

OBJECTIVE: We conducted a prospective naturalistic study of pregnant women with bipolar disorder (BD) to evaluate symptoms of BD across childbearing and assess whether pharmacotherapy reduced their severity. METHODS: Assessments were scheduled at 20, 30, and 36 weeks' gestation and 2, 12, 26, and 52 weeks postpartum. Symptoms were assessed using the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Supplement (SIGH-ADS) and Mania Rating Scale (MRS). RESULTS: Pregnant women (N=152) with BD were evaluated; 88 women (58%) were treated and 64 untreated (42%) with psychotropic drugs during pregnancy. Among the 88 women treated, 23 (26%) discontinued their medication in the first trimester and the remaining 65 (74%) were exposed throughout pregnancy or in the second and third trimesters. More than two-thirds (73%) of the women who remained in the study took psychotropic agents postpartum. The mean scores on the SIGH-ADS were in the mild range of depressive symptoms in both the psychotropic-treated and untreated groups in both pregnancy and postpartum. The majority of women had no or few symptoms of mania. Of the pregnant women treated with psychotropic agents, 66% received a guideline-concordant drug, and 34% received either antidepressant monotherapy (for BD I) or mono- or polypharmacy with a variety of other agents. CONCLUSIONS: This sample of perinatal women with BD was characterized by mild residual symptoms of depression independent of pharmacotherapy, which poses a risk for recurrence and impaired parenting. The treatment of childbearing women with BD deserves urgent clinical and research attention to improve psychiatric outcomes.

Right Frontoinsular Cortex and Subcortical Activity to Infant Cry Is Associated with Maternal Mental State Talk.

The study objective was to examine neural correlates of a specific component of human caregiving: maternal mental state talk, reflecting a mother's proclivity to attribute mental states and intentionality to her infant. Using a potent, ecologically relevant stimulus of infant cry during fMRI, we tested hypotheses that postpartum neural response to the cry of "own" versus a standard "other" infant in the right frontoinsular cortex (RFIC) and subcortical limbic network would be associated with independent observations of maternal mental state talk. The sample comprised 76 urban-living, low socioeconomic mothers (82% African American) and their 4-month-old infants. Before the fMRI scan, mothers were filmed in face-to-face interaction with their infant, and maternal behaviors were coded by trained researchers unaware of all other information about the participants. The results showed higher functional activity in the RFIC to own versus other infant cry at the group level. In addition, RFIC and bilateral subcortical neural activity (e.g., thalamus, amygdala, hippocampus, putamen) was associated positively with maternal mental state talk but not with more global aspects of observed caregiving. These findings held when accounting for perceptual and contextual covariates, such as maternal felt distress, urge to help, depression severity, and recognition of own infant cry. Our results highlight the need to focus on specific components of caregiving to advance understanding of the maternal brain. Future work will examine the predictive utility of this neural marker for mother-child function. SIGNIFICANCE STATEMENT: The current study advances extant literature examining the neural underpinning of early parenting behavior. The findings highlight the special functional importance of the right frontoinsular cortex-thalamic-limbic network in a mother's proclivity to engage in mental state talk with her preverbal infant, a circumscribed aspect of maternal caregiving purported to be a prerequisite of sensitive and responsive caregiving. These associations existed specifically for maternal mentalizing behavior and were not evident for more generic aspects of caregiving in this urban sample of 76 postpartum mothers. Finally, the findings were robust even when controlling for potential demographic, perceptual, and contextual confounds, supporting the notion that these regions constitute an innate, specialized maternal mentalizing network.

Predicting adolescent postpartum caregiving from trajectories of depression and anxiety prior to childbirth: a 5-year prospective study.

Symptoms of depression and anxiety in pregnancy have been linked to later impaired caregiving. However, mood symptoms are often elevated in pregnancy and may reflect motherhood-specific concerns. In contrast, little is known about the effects of prepregnancy depression and anxiety on postpartum caregiving. Understanding these developmental risk factors is especially important when childbearing also occurs during adolescence. The sample comprised 188 adolescent mothers (ages 12-19 years) who had participated in a longitudinal study since childhood. Mothers were observed in face-to-face interaction with the infant at 4 months postpartum, and caregiving behaviors (sensitivity, hostile-intrusive behavior, and mental state talk) were coded independently. Data on self-reported depression and anxiety gathered in the 5 years prior to childbirth were drawn from the large-scale longitudinal study. Parallel process latent growth curve models revealed unique effects of distal anxiety and slow decline in anxiety over time on lower levels of maternal mental state talk after accounting for the overlap with depression development. Depressive symptoms showed significant stability from distal measurement to the postpartum period, but only concurrent postpartum mood was associated with poorer quality of maternal speech. The results highlight specific targets for well-timed preventive interventions with vulnerable dyads.

Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 µg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing.

Impact of colocated behavioral health on OB-GYN clinicians' rate of perinatal behavioral health diagnosis and psychotropic prescription.

OBJECTIVE: To examine the association of colocated behavioral health(BH) care with rates of OB-GYN clinician coding of BH diagnoses and BH medications. METHOD: Using 2 years of EMR data from perinatal individuals treated across 24 OB-GYN clinics, we tested the hypothesis that colocated BH care would increase rates of OB-GYN BH diagnoses and psychotropic prescription. RESULTS: Psychiatrist integration(0.1 FTE) was associated with 45.7% higher odds of OB-GYN coding for BH diagnoses and BH clinician integration was associated with 25% lower odds of OB-GYN BH diagnosis and 37.7% lower odds of BH medication prescription. Non-white patients had 28-74% and 43-76% lower odds of having a BH diagnosis and a BH medication ordered, respectively. The most common diagnoses were anxiety and depressive disorders(60%) and the most prescribed BH medications were SSRIs(86%). CONCLUSIONS: OB-GYN clinicians made fewer BH diagnoses and prescribed fewer psychotropics after 2.0 FTE BH clinician integration, a possible indication of external referrals for BH treatment. Non-white patients received BH diagnoses and medications less often than white patients. Future research in real world implementation of BH integration in OB-GYN clinics should examine fiscal strategies that support BH care manager-OB-GYN collaboration as well as methods to ensure equitable delivery of BH care.

Preconception interpersonal personality features predict postpartum maternal parenting behaviors.

Individual differences in personality traits affect the quality of social relationships. The parent-child relationship is among the most impactful social relationships in an individual's life, and positive parenting behaviors are known to support positive child development. The present study aimed to identify personality predictors-measured prior to conception at age 16-on later positive parenting behaviors. Young women (n = 207; 83.5% Black or multiracial; 86.9% receiving public assistance) who were followed since childhood as part of a prospective longitudinal study were observed interacting with their infants 4 months postpartum. We tested prospective associations between personality factors relevant to the quality and maintenance of social relationships-empathy, callousness, and rejection sensitivity-and coded dimensions of parenting behavior: maternal warmth, responsiveness, and mental state talk. We additionally examined potential moderating effects of infant affect on the relations between personality and parenting behavior. Results indicated that preconception empathy predicted later maternal warmth and responsivity, whereas preconception callousness was inversely associated with maternal warmth. The association between rejection sensitivity and maternal mental state talk was moderated by infant affect, consistent with a "goodness-of-fit" framework. The present study is the first to our knowledge to report associations between preconception personality and later parenting behaviors. The findings suggest that a woman's personality traits in adolescence, potentially years before she becomes a mother, can predict her behavior during interactions with her infant. Clinically, findings suggest the potential for interventions in adolescence to influence later parenting behavior and ultimately impact children's developmental outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An intensive outpatient program for suicidal college students.

Objective: College counseling centers (CCCs) have limited capacity to accommodate high-risk students who need more intensive care than traditional outpatient treatment. We describe an Intensive Outpatient Program (IOP) to meet the specialized needs of suicidal undergraduates. Participants: Suicidal undergraduates aged 18-24. Methods: Fact-gathering meetings with local universities confirmed high need for prompt access to IOP care for students presenting in crisis at CCCs and emergency rooms, and post-inpatient discharge. We thus iteratively designed and implemented the College Option Services for Teens at Risk (COSTAR) IOP. Results: The 6-week program includes initial diagnostic evaluation and risk assessment followed by weekly skills groups, individual therapy, and medication management. Between September 2017 and January 2020, 148 students (M age = 19.7) attended an average of 5.7 COSTAR group sessions (SD = 4.7). Conclusions: A specialty IOP for suicidal college students holds promise in a stepped care approach for at-risk college students.

Reduced postpartum hippocampal volume is associated with positive mother-infant caregiving behavior.

BACKGROUND: Maternal caregiving is a complex set of behaviors that can be impacted by early life stress (ELS), yet human neurobiological mechanisms are not well understood. METHODS: Young mothers (n=137) were enrolled into a neuroimaging substudy of the longitudinal Pittsburgh Girls Study (PGS). Using data collected annually while subjects were ages 8-16, ELS was calculated as a composite score of poverty, trauma, and difficult life circumstances. At 4 months postpartum, mothers underwent neuroimaging and filmed mother-infant interaction. Maternal caregiving was coded along 6 dimensions yielding "positive" and "negative" components of caregiving. Participants' MPRAGE images were subjected to preprocessing and voxel-based morphometry (VBM) to quantify vmPFC, amygdala and hippocampus gray matter (GM) volume. We used hierarchical linear regression to investigate the relationship between GM volume and maternal caregiving, covarying for ELS as well as maternal age, weeks postpartum, race and postpartum depression score. RESULTS: Hippocampal GM volume was inversely associated with independent observations of positive maternal caregiving. Similar findings in the vmPFC did not remain significant after correction for multiple comparisons. ELS, particularly physical assault, was associated with reduced GM volumes but was unrelated to observed maternal caregiving. LIMITATIONS: Our single-timepoint MRI-based GM volume method was not able to demonstrate time-related intra-individual perinatal neuroplasticity, nor could it resolve neural subregions involved in caregiving-related plasticity. CONCLUSIONS: Our findings shed light on the putative plasticity of the human maternal extra-hypothalamic stress-circuitry underlying positive maternal caregiving behavior. Whether reduced hippocampal GM volume represents pruning or represents neural resilience in the face of ELS, remains to be studied.

Medial prefrontal cortex 5-HT(2A) density is correlated with amygdala reactivity, response habituation, and functional coupling.

Feedback inhibition of the amygdala via medial prefrontal cortex (mPFC) is an important component in the regulation of complex emotional behaviors. The functional dynamics of this corticolimbic circuitry are, in part, modulated by serotonin (5-HT). Serotonin 2A (5-HT(2A)) receptors within the mPFC represent a potential molecular mechanism through which 5-HT can modulate this corticolimbic circuitry. We employed a multimodal neuroimaging strategy to explore the relationship between threat-related amygdala reactivity, assessed using blood oxygen level-dependent functional magnetic resonance imaging, and mPFC 5-HT(2A) density, assessed using [(18)F]altanserin positron emission tomography in 35 healthy adult volunteers. We observed a significant inverse relationship wherein greater mPFC 5-HT(2A) density was associated with reduced threat-related right amygdala reactivity. Remarkably, 25-37% of the variability in amygdala reactivity was explained by mPFC 5-HT(2A) density. We also observed a positive correlation between mPFC 5-HT(2A) density and the magnitude of right amygdala habituation. Furthermore, functional coupling between the amygdala and mPFC was positively correlated with 5-HT(2A) density suggesting that effective integration of emotionally salient information within this corticolimbic circuitry may be modulated, at least in part, by mPFC 5-HT(2A). Collectively, our results indicate that mPFC 5-HT(2A) is strongly associated with threat-related amygdala reactivity as well as its temporal habituation and functional coupling with prefrontal regulatory regions.

Implementation of perinatal collaborative care: a health services approach to perinatal depression care.

AIM: Our objective was to integrate lessons learned from perinatal collaborative care programs across the United States, recognizing the diversity of practice settings and patient populations, to provide guidance on successful implementation. BACKGROUND: Collaborative care is a health services delivery system that integrates behavioral health care into primary care. While efficacious, effectiveness requires rigorous attention to implementation to ensure adherence to the core evidence base. METHODS: Implementation strategies are divided into three pragmatic stages: preparation, program launch, and program growth and sustainment; however, these steps are non-linear and dynamic. FINDINGS: The discussion that follows is not meant to be prescriptive; rather, all implementation tasks should be thoughtfully tailored to the unique needs and setting of the obstetric community and patient population. In particular, we are aware that implementation on the level described here assumes commitment of both effort and money on the part of clinicians, administrators, and the health system, and that such financial resources are not always available. We conclude with synthesis of a survey of existing collaborative care programs to identify implementation practices of existing programs.

Transdermal estradiol for postpartum depression: a promising treatment option.

Postpartum depression (PPD) is the most common unrecognized complication of childbirth and affects 1 out of 7 childbearing women. Although conventional pharmacologic and psychotherapeutic antidepressant treatments are effective for PPD, a natural alternative may be preferred by postpartum women, especially those who breastfeed their infants. The treatment of PPD with synthetic forms of naturally occurring estrogen is mechanistically appealing because PPD occurs in the context of estrogen withdrawal at parturition. Preliminary evidence suggests that PPD is a disorder of hormone-related mood dysregulation (similar to perimenopausal depression) that can be effectively treated with estrogen. This review provides the basic science and clinical background as well as safety considerations to support the application of transdermal estradiol as a treatment for PPD. We conclude that estradiol treatment for PPD requires confirmation of efficacy in a randomized clinical trial before routine clinical use as monotherapy. Additional data regarding maternal tolerability of cyclic progestins, long-term safety of estradiol treatment, estradiol passage into breast milk and infants, and interdisciplinary collaboration among psychiatrists and gynecologists is also needed before estradiol is used in women who decline or fail to respond to first-line antidepressant treatments, or as an augmentation of conventional antidepressant treatment.

Serotonin-1A receptor imaging in recurrent depression: replication and literature review.

INTRODUCTION: Serotonin-1A receptor (5-HT1AR) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT1AR agonists in vivo and to 5-HT1AR binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT1AR binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635, and we have demonstrated reduced 5-HT1AR BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders (n=12) versus controls (n=8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 1999;46(10):1375-87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. METHODS: Using PET and [carbonyl-(11)C]WAY-100635, 5-HT1AR BP was assessed in 16 depressed subjects and 8 healthy controls. RESULTS: Mean 5-HT1AR BP was reduced by 26% in the MTC (P<.005) and by 43% in the raphe (P<.001) in depressives versus controls. CONCLUSIONS: These data replicate our original findings, which showed that BP was reduced by 27% in the MTC (P<.025) and by 42% in the raphe (P<.02) in depression. The magnitudes of these reductions in 5-HT1AR binding were similar to those found postmortem in 5-HT1AR mRNA concentrations in the hippocampus in MDD [López JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73] and in 5-HT1AR-binding capacity in the raphe in depressed suicide victims [Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001;25(6):892-903]. There exists disagreement within the literature, however, regarding the presence and direction of 5-HT1AR-binding abnormalities in depression, which may be explained in some cases by differences in anatomical location (e.g., [Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression--postmortem evidence for decreased serotonin activity. J Neurosci 1998;18(18):7394-401]) and in other cases by pathophysiological heterogeneity within MDD (e.g., some depressives hypersecrete cortisol, which would be expected to down-regulate 5-HT1AR expression [López JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73]). Antidepressant drug treatment does not alter these abnormalities in 5-HT1AR binding [Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000;57(2):174-80; Moses-Kolko EL, Price JC, Thase ME, Meltzer CC, Kupfer DJ, Mathis CA, Bogers WD, Berman SR, Houck PR, Schneider TN, Drevets WC. Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635. Synapse 2007;61(7):523-30] but may compensate for blunted 5-HT1AR function by increasing post-synaptic 5-HT1AR transmission [Chaput Y, de Montigny C, Blier P. Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 1991;5(4):219-29].

Postpartum depressive symptoms moderate the link between mothers' neural response to positive faces in reward and social regions and observed caregiving.

Postpartum depression may disrupt socio-affective neural circuitry and compromise provision of positive parenting. Although work has evaluated how parental response to negative stimuli is related to caregiving, research is needed to examine how depressive symptoms during the postpartum period may be related to neural response to positive stimuli, especially positive faces, given depression's association with biased processing of positive faces. The current study examined the association between neural response to adult happy faces and observations of maternal caregiving and the moderating role of postpartum depression, in a sample of 18- to 22-year old mothers (n = 70) assessed at 17 weeks (s.d. = 4.7 weeks) postpartum. Positive caregiving was associated with greater precuneus and occipital response to positive faces among mothers with lower depressive symptoms, but not for those with higher symptoms. For mothers with higher depressive symptoms, greater ventral and dorsal striatal response to positive faces was associated with more positive caregiving, whereas the opposite pattern emerged for mothers with lower symptoms. There was no association between negative caregiving and neural response to positive faces or negative faces. Processing of positive stimuli may be an important prognostic target in mothers with depressive symptoms, given its link with healthy caregiving behaviors.

Telephone-Based Depression Care Management for Postpartum Women: A Randomized Controlled Trial.

OBJECTIVE: With a period prevalence of 21.9% in the year after birth, depression is a common complication of childbearing. We assessed the impact of telephone-delivered depression care management (DCM) on symptom levels, health service utilization, and functional status 3, 6, and 12 months postpartum. METHODS: The randomized controlled trial was conducted at the University of Pittsburgh, Pittsburgh, Pennsylvania, from March 2006 through September 2010. Women (N = 628) who screened positive for depression (a score of 10 or greater on the Edinburgh Postnatal Depression Scale) 4 to 6 weeks postpartum were evaluated with the Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition With Psychotic Screen and enrolled in a randomized trial of DCM compared to enhanced usual care (EUC). Clinicians conducted telephone contacts to educate, assist with treatment decisions, monitor symptoms, facilitate access to services, and encourage links to community resources. Independent evaluators collected symptom scores, functional status, and health services use at 3, 6, and 12 months postpartum. Primary outcome was reduction of symptoms as measured by the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement. RESULTS: Mean depressive symptom and function scores significantly improved (by greater than 50%) in both groups of women but did not differ by DCM versus EUC assignment. Health services use was similar in women randomly assigned to DCM compared to EUC. Women with childhood sexual abuse responded significantly more favorably to DCM on depression and functional measures (all P values < .02). CONCLUSIONS: Both DCM and EUC favorably impacted depression symptom levels and function. The subgroup of women with childhood sexual abuse benefited significantly more from DCM compared to the EUC condition. Regular telephone availability of a clinician is a resource that appears to be particularly therapeutic to women with childhood sexual abuse. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00282776.

The influence of motherhood on neural systems for reward processing in low income, minority, young women.

OBJECTIVE: Given the association between maternal caregiving behavior and heightened neural reward activity in experimental animal studies, the present study examined whether motherhood in humans positively modulates reward-processing neural circuits, even among mothers exposed to various life stressors and depression. METHODS: Subjects were 77 first-time mothers and 126 nulliparous young women from the Pittsburgh Girls Study, a longitudinal study beginning in childhood. Subjects underwent a monetary reward task during functional magnetic resonance imaging in addition to assessment of current depressive symptoms. Life stress was measured by averaging data collected between ages 8-15 years. Using a region-of-interest approach, we conducted hierarchical regression to examine the relationship of psychosocial factors (life stress and current depression) and motherhood with extracted ventral striatal (VST) response to reward anticipation. Whole-brain regression analyses were performed post-hoc to explore non-striatal regions associated with reward anticipation in mothers vs nulliparous women. RESULTS: Anticipation of monetary reward was associated with increased neural activity in expected regions including caudate, orbitofrontal, occipital, superior and middle frontal cortices. There was no main effect of motherhood nor motherhood-by-psychosocial factor interaction effect on VST response during reward anticipation. Depressive symptoms were associated with increased VST activity across the entire sample. In exploratory whole brain analysis, motherhood was associated with increased somatosensory cortex activity to reward (FWE cluster forming threshold p<0.001). CONCLUSIONS: These findings indicate that motherhood is not associated with reward anticipation-related VST activity nor does motherhood modulate the impact of depression or life stress on VST activity. Future studies are needed to evaluate whether earlier postpartum assessment of reward function, inclusion of mothers with more severe depressive symptoms, and use of reward tasks specific for social reward might reveal an impact of motherhood on reward system activity.

Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications.

CONTEXT: A neonatal behavioral syndrome linked to in utero serotonin reuptake inhibitor (SRI) exposure during the last trimester of pregnancy has been identified. The US Food and Drug Administration (FDA) and drug manufacturers have recently agreed to a class labeling change for SRIs, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), to include information about potential adverse events in neonates exposed in utero. Integration of data about the neonatal behavioral syndrome into the management of pregnancy in women who take SRIs is a current challenge for physicians. OBJECTIVES: To review evidence regarding the SRI-related neonatal syndrome and to help clinicians guide their patients in a risk-benefit decision-making process. DATA SOURCES: We searched MEDLINE (1966-February 2005) and PsycINFO (1974-February 2005). All articles related to neonatal signs after in utero SRI exposure were acquired, as well as unpublished data on this topic from the FDA advisory committee meeting of June 2004. References cited in case reports and studies were reviewed. Foreign-language literature was included and translated to English. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they had clearly identified maternal SRI exposure for a minimum of the final trimester of pregnancy through delivery and assessed neonatal outcomes. We identified 13 case reports describing a total of 18 cases. Nine cohort studies met criteria. When not included in the published article, relative risks and 95% confidence intervals (CIs) were computed from raw data and summary risk ratios and 95% CIs were determined with Mantel-Haenszel estimates. DATA SYNTHESIS: Compared with early gestational SRI exposure or no exposure, late SRI exposure carries an overall risk ratio of 3.0 (95% CI, 2.0-4.4) for a neonatal behavioral syndrome. The most SRI-related neonatal case reports involved fluoxetine and paroxetine exposures. Neonates primarily display central nervous system, motor, respiratory, and gastrointestinal signs that are usually mild and disappear by 2 weeks of age. Medical management has consisted primarily of supportive care in special care nurseries. A severe syndrome that consists of seizures, dehydration, excessive weight loss, hyperpyrexia, or intubation is rare in term infants (1/313 quantifiable cases). There have been no reported neonatal deaths attributable to neonatal SRI exposure. CONCLUSIONS: Available evidence indicates that in utero exposure to SRIs during the last trimester through delivery may result in a self-limited neonatal behavioral syndrome that can be managed with supportive care. The risks and benefits of discontinuing an SRI during pregnancy need to be carefully weighed for each individual patient. Development and validation of assessment methods and clinical management strategies are critical to advancing this research.

Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women.

OBJECTIVE: To use statistical parametric mapping to determine the extent of previously reported serotonin type 2A (5HT(2A)) receptor binding potential (BP) increases in postmenopausal women following hormone therapy. DESIGN: Repeated measures positron emission tomography (PET) study. SETTING: Academic research environment. PATIENT(S): Five healthy, postmenopausal women. INTERVENTION(S): Serial PET images of [(18)F]altanserin uptake were acquired to measure 5HT(2A) receptor BP at menopausal baseline, following estradiol (E(2)), and following combined E(2) + micronized progesterone (P(4)). MAIN OUTCOME MEASURE(S): 5HT(2A) receptor BP. RESULT(S): Combined E(2) + P(4) treatment was associated with significant increases in the 5HT(2A) receptor BP increases in widespread areas of cerebral cortex. Treatment with E(2) alone was also associated with widespread cortical BP increases, although these changes reached statistical significance in fewer regions. The rate of [(18)F]altanserin metabolism was significantly decreased in the E(2) + P(4) condition relative to menopausal baseline, but this difference did not appear to correlate with changes in 5HT(2A) receptor BP. CONCLUSION(S): Estradiol priming followed by combined E(2) + P(4) is associated with widespread increases in 5HT(2A) receptor BP in the cerebral cortex, consistent with the E(2)-associated increases in 5HT(2A) receptor density previously observed in experimental animals.

Disrupted posterior cingulate-amygdala connectivity in postpartum depressed women as measured with resting BOLD fMRI.

Disengagement of emotion regulation circuits was previously shown in depressed mothers and was hypothesized to underlie the impaired maternal-infant sensitivity described in postpartum depression (PPD). We hypothesized similarly reduced resting-state functional connectivity in default mode network (DMN) regions involved in social cognition in PPD. Resting-state functional MRI, clinical and mother-infant attachment data were obtained from 14 unmedicated postpartum women with major depression and 23 healthy postpartum women. Posterior cingulate cortex (PCC) time series were extracted, filtered between 0.007 and 0.08 Hz and used as regressors in a whole brain general linear model analysis. PCC-right amygdala connectivity was significantly disrupted in depressed compared to healthy mothers for low-frequency neural activity, showing a negative (inverse) coupling in the depressed group but not in the controls. PCC-right amygdala connectivity was positively correlated with PCC-parahippocampus connectivity. Resting connectivity patterns of positive co-activations in postpartum women mirrored the canonical DMN. These findings of reduced PCC-amygdala coupling raise the possibility that PPD might involve the disruption of outward, preventative aspects of self-relevant thought and theory of mind/empathy processes. Further integrated studies of neural connectivity and these cognitive/behavioral dimensions are warranted.