Relationships between neuroactive steroids, GABA and glutamate MRS and functional connectivity in postpartum depression Yiling Wang1 , MS, Kristina M. Deligiannidis1,2 , MD
1Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 2Division of Psychiatry Research, Women’s Behavioral Health, Zucker
Hillside Hospital,
Northwell Health, New York, NY
Background
Methods
One in eight women are affected by postpartum depression (PPD), a psychiatric illness defined as major depressive disorder (MDD) with peripartum onset 1. PPD has a negative impact on infant brain development 2 and can contribute to severe consequences such as maternal and infant mortality by suicide or infanticide, respectively3,4. Currently, the paucity of knowledge on the pathophysiology of PPD with regards to the neurochemistry and neurocircuitry contributes to the low diagnosis and treatment rates of PPD5. In animal models, hormonal changes across the peripartum period is associated with normal neuroplasticity of GABA and glutamate (GLU) systems, while PPD is correlated with abnormal NAS and GABA and GLU neuroplasticity 7. Changes in neuroactive steroids (NAS) that occur during female reproductive years and peripartum are thought to contribute to the higher prevalence of major depressive disorder (MDD) among women 6 through their modulation of the glutamatergic and GABAergic function in various regions of the brain 8.
Participants: • Antepartum onset unipolar MDD • Ages 18-40 • 24-34 weeks gestation or earlier Exclusion Criteria: • Bipolar or psychotic disorder, suicidality • Substance or nicotine use in the past 12 mo. • Any psychotropic, steroid or hormone use • MRI contraindications Research Procedure: • Urine hCG and Drug Testing • Maternal blood: neuroactive steroids, including allopregnanolone • Resting-state fMRI to determine neural connectivity • 1H-MRS (magnetic resonance spectroscopy) to determine neurochemistry (GABA, GLU) • This is a prospective observational study in which we will look for differences in neurochemistry and neurocircuitry among the three groups: PPD, HPCW, HFCW
Objective & Hypothesis Objective: to determine how GABAergic and glutamatergic NAS and default mode network (DMN) resting-state functional connectivity (RSFC) compare among: 1) peripartum women who suffer from PPD, 2) healthy peripartum control women (HPCW), 3) healthy non-postpartum women during the follicular phase of menstrual cycle (HFCW) Hypothesis: The high-level, sustained NAS exposure and withdrawal during the peripartum period is associated with differential cortical GABA and GLU concentrations and DMN RSFC compared to the low-level, brief NAS exposure and withdrawal during the menstrual cycle. We also hypothesize that we would see further differences between peripartum women with and without PPD.
Visit 1
24-34 Weeks Gestation
Informed consent, psychiatric and medical interviews, blood and urine testing
Visit 2
34-40 Weeks Gestation
Psychiatric and medical interviews, blood and urine testing
Visit 3
2-6 Weeks Postpartum
Psychiatric and medical interviews, blood and urine testing, MRI brain scan
Visit 4
6-10 Weeks Postpartum
Psychiatric and medical interviews, blood and urine testing
Results Results This is an actively enrolling study and results are therefore not yet available. Expected date of completion is 2025.
Future Directions To determine RSFC endophenotypes across different PPD phenotypes, such as anxiousdepressed vs. anhedonic-depressed4. Predict response to antidepressants (i.e., SSRIs and GABAergic brexanolone5) based on phenotype Determine target engagement of investigational antidepressants like SAGE-217and ganaxolone
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