Depression in Women During Childbearing Years: Causes, Symptoms, Challenges & Treatment

During pregnancy and the postpartum period, two notably major life events for women, significant hormonal changes take place that increase vulnerability for depression. At the same time, many women during these periods find themselves in stressful situations exacerbated by the changes in life circumstances inherent with having children. While the vast majority of women adjust successfully to pregnancy and motherhood, some portion of women find the everyday challenges exceedingly difficult to manage. For these women the childbearing years can be the “perfect storm” for major depressive disorder (MDD)

Pilot Project Funding Opportunities

Learn about funding opportunities offered through the UMCCTS in the 2013-2014 academic year. A previously-funded researcher (Kristina Deligiannidis) also describes her project, Neuroendocrine & neuroimaging endophenotypes in perinatal depression. View a video of Kristina Deligiannidis\u27 presentation (34 min.)

Disrupted Resting-State Functional Connectivity in Medication-free Women with Postpartum Depression

Background: Women are at increased risk of developing depression in the postpartum, a time of gonadal steroid flux. Abnormalities of gonadal steroids have been identified in some depressed women at times of reproductive flux. Gonadal steroids modulate corticocortical and corticolimbic functional connectivity (FC) in healthy, non-puerperal subjects; however there are no published studies of FC in postpartum depression (PPD). Methods: Healthy comparison (HCS) (n=9) and medication-free subjects with unipolar PPD (n=8) were scanned at 3-9 weeks postpartum (using 3T Philips MRI) while ‘at rest’ with eyes open. Data analysis was carried out using SPM-8 and Data Processing Assistant for Resting-State fMRI (DPARSF) to perform seed based resting-state functional connectivity (rs-FC) analysis. Seeds were placed at bilateral anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC), hippocampi (HIPP) and amygdalae (AMYG). Correlation coefficients obtained from individual subject analysis were used in performing two-sample t-test to compare the two cohorts. Results: Functional connectivity maps revealed a more distributed pattern of connectivity with each seed (i.e. ACC, DLPFX, HIPP, and AMYG) for HCS than PPD. In PPD subjects as compared to HCS, there was attenuation of rs-FC between corticocortical and corticolimbic areas. Conclusions: In the early postpartum period, rs-FC patterns are disrupted in women with PPD in brain regions important for cognition, affect and the stress response. Larger studies are necessary to elucidate the role of disrupted neural connections in the pathophysiology of PPD and the potential modulatory role of gonadal steroids in women

The impact of pregnancy on the pharmacokinetics of antiseizure medications:A systematic review and meta-analysis of data from 674 pregnancies

Objective: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. Methods: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. Results: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07–2.45, 0.42, range 0.08–0.82 and 0.52, range 0.04–2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10−3, 95%CI = -16.08 to −8.58 × 10−3 (μg/mL)/(mg/day), p &lt; 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to −4.36, p &lt; 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to −0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10−3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10−3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. Conclusions: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.</p

The impact of pregnancy on the pharmacokinetics of antiseizure medications:A systematic review and meta-analysis of data from 674 pregnancies

Objective: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. Methods: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. Results: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07–2.45, 0.42, range 0.08–0.82 and 0.52, range 0.04–2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10−3, 95%CI = -16.08 to −8.58 × 10−3 (μg/mL)/(mg/day), p &lt; 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to −4.36, p &lt; 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to −0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10−3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10−3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. Conclusions: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.</p

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Background The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods. Methods Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19–40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the ten-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes. Findings Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe. Interpretation Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression

Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures

Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety

The physician-scientist workforce in the United States

The lack of research dollars dedicated to understanding the pathophysiology and treatment of psychiatric disorders is a barrier not only to making significant medical advances for our patients but also to developing the physician–scientist workforce to fuel those advances

Therapeutic drug monitoring in pregnant and postpartum women: recommendations for SSRIs, lamotrigine, and lithium

Recently, guidelines for antenatal management of depression were published.1 Psychotherapy alone may be an appropriate treatment for some women, while psychopharmacotherapy may be indicated in others. Use of psychopharmacotherapy during pregnancy and the postpartum involves complex clinical decisions based on the risks and benefits and alternatives to medications. The aim of effective treatment is to minimize maternal and fetal exposure to psychiatric illness by optimally treating it with the minimum effective dose regimen. One variable that complicates psychopharmacotherapy is that dosing often requires adjustment to maintain therapeutic effects, particularly in late pregnancy. The current article focuses on those factors that affect dosing in pregnancy