Women's Reproductive Mood Disorders PDF

Women’s Reproductive Mood Disorders November 14th, 2024  Housekeeping: The Rest of the Semester  November 26th: Midterm #2  December 5th: Research Proposal due via UR courses  November 28th-December 5th: 3MT-style presentations  Send me your slide the day before...

Women’s Reproductive Mood Disorders November 14th, 2024  Housekeeping: The Rest of the Semester  November 26th: Midterm #2  December 5th: Research Proposal due via UR courses  November 28th-December 5th: 3MT-style presentations  Send me your slide the day before your presentation Research Proposal Evaluation Rubric Background Comments Provides a comprehensive, clear overview of 0 1 2 3 4 5 /10 the relevant literature. Problem Statement & Goal Provides a convincing argument that there is an important gap in our knowledge about this 0 1 2 3 4 5 /5 topic that needs to be addressed. The project goal is clear. Methods & Hypotheses Provides a clear description of the proposed methods (participants, study design, 0 1 2 3 4 5 /10 questionnaires to be used) and provides a good rationale for the methods chosen. Hypotheses are clear. Anticipated results and implications Makes reasonable predictions about potential 0 1 2 3 4 5 /5 results and is clear about how each outcome may influence current knowledge or practice Strengths and Limitations Provides a thoughtful overview of the 0 1 2 3 4 5 /5 proposed study’s strengths and limitations. Overall /35  3-Minute Thesis Presentation  3-minute presentation about your research proposal  Accompanied by 1 PowerPoint slide  A chance to tell us about your exciting project!  3-Minute Thesis Presentation  Tips  Remember the question “so what?”  Think carefully about what to include on your 1 slide  Most Common Mistakes  Too much detail  Sounding too scripted  Monotonous voice  https://www.youtube.com/watch?v=0K9iYUBCG_o Why Postpartum Depression (PPD)? Hormonal influences ? PPD  Bloch et al., 2000  Does postpartum depression result from an increased sensitivity to hormonal withdrawal?  Participants  8 women with & 8 without a history of postpartum depression ≥1 year since childbirth No history of depression unrelated to postpartum No PMDD  Bi-monthly psychological questionnaires Bloch, M., Schmidt, P.J., Danaceau, M., Murphy, J., Nieman, L., Rubinow, D.R. (2000). American Journal of Psychiatry, 157(6), 924-930.  Bloch et al., 2000  Study Design  Timeline  Months 1 & 2: nothing (Baseline)  Month 3 & 4: (Addback) Leuprolide Estradiol (10 mg!) Progesterone (dose based on blood level targets)  Month 5: Leuprolide + placebo (Withdrawal)  Months 6 & 7: nothing (Follow Up) Results Results  Conclusion  Withdrawal from high levels of estradiol & progesterone induces depressive symptoms in women with a history of postpartum depression but not those without  Suggests that postpartum depression is an abnormal response to a normal fluctuation in hormones  Limitation: can’t separate the effects of estradiol & progesterone What is the specific hormonal trigger for PPD? What is the specific hormonal trigger for PPD?  Progesterone  Small observational studies have not seen a correlation between progesterone and mood  BUT those studies did not look at progesterone-derived neurosteroids… Yim et al. (2015), Annual Review of Clinical Psychology, 11, 99-137.  Remember Allopregnanolone (ALLO)?  A “positive allosteric modulator” of the GABAA receptor  This means that it increases GABA activity without actually binding to the GABA receptor  What’s GABA?  GABA stands for gamma-aminobytyric acid  Is the chief inhibitory neurotransmitter in the brain: it reduces neuronal excitability  GABAergic activity increases when you drink alcohol or an anti- anxiety pill  ALLO & PPD in Bloch et al., 2000  In women with a history of PPD, change in ALLO during the hormone addback phase negatively correlated with dep sx:  This correlation was not seen in the women without a history of PPD  Conclusion: PPD may partly result from an increased sensitivity to ALLO withdrawal Schiller et al., 2014, Psychopharmacology, 231: 3557-3567.  Brexanolone Trial  Brexanolone = synthetic form of ALLO  Participants: women with moderate-severe PPD (onset within 4 weeks, currently within 6 months postpartum)  Study 1  Randomized to 1 of 3 groups:  1 injection Brexanolone, 90 μg/kg  1 injection Brexanolone, 60 μg/kg  1 injection of placebo  Study 2  Randomized to placebo or Brexanolone, 60 μg/kg  Outcome: HAM-D score for 30 days Meltzer-Brody et al., 2018, Lancet, 392, 105-1070.  Brexanolone Trial Meltzer-Brody et al., 2018, Lancet, 392, 105-1070.  Brexanolone Trial Meltzer-Brody et al., 2018, Lancet, 392, 105-1070.  Brexanolone Trial  One injection of synthetic ALLO improved depressive symptoms compared to placebo  Suggests that withdrawal from ALLO may trigger the onset of PPD  May 2019: Brexanolone is FDA-approved for the treatment of PPD Meltzer-Brody et al., 2018, Lancet, 392, 105-1070. What is the specific hormonal trigger for PPD?  Oxytocin? Yim et al. (2015), Annual Review of Clinical Psychology, 11, 99-137.  Oxytocin  Oxytocin is produced in the hypothalamus  From there:  Oxytocin neurons in the hypothalamus project to the limbic system to influence emotion (acts as neurotransmitter)  Oxytocin is transported to the pituitary gland for release into the blood (acts as hormone)  Is stress-responsive and dampens the HPA axis  Commonly known as the “love hormone”  Released in response to positive social interaction  Promotes social behaviour, facilitates bonding  Is critical for breastfeeding  Oxytocin & PPD  Some evidence that lower levels of oxytocin during pregnancy and postpartum are associated with PPD  Also some research suggesting that women with PPD may respond differently to breastfeeding-induced increases in oxytocin… Yim et al. (2015), Annual Review of Clinical Psychology, 11, 99-137. Response to Breastfeeding-Induced Oxytocin 47 women categorized into: 1. breastfeeding with PPD 2. breastfeeding without PPD 3. not breastfeeding Women completed a feeding session, blood samples, and the TSST during the 3 trimester, 2 and 8 weeks postpartum Stuebe et al. (2015). Psychneuroendocrinology, 55, 164-172.  Oxytocin & Stress-Induced Cortisol Stuebe et al. (2015). Psychneuroendocrinology, 55, 164-172.  Oxytocin & Stress-Induced Cortisol Stuebe et al. (2015). Psychneuroendocrinology, 55, 164-172.  Oxytocin & PPD  Oxytocin in the postpartum period plays an important role as an anxiolytic, in facilitating bonding with baby, and in facilitating breastfeeding  Oxytocin seems to have an anxiogenic (rather than anxiolytic) effect in women with PPD  Could help explain why PPD and breastfeeding difficulties often go hand-in-hand Why Postpartum Depression (PPD)? Hormona Increase l d stress influence s PPD Answer is likely both – the contribution of one vs. the other may differ from woman to woman  Observational study of 9,848 women in the U.K. and their children’s outcomes  EPDS score assessed 2, 8, 21, 33, 61, 73, 93 and 134 months postpartum  Severity & chronicity of symptoms assessed  Not persistent PPD = high score only at month 2  Persistent PPD = high score at months 2 & 8  Statistically adjusted for maternal education  Results All levels of severity and chronicity are associated with offspring behavioral problems at 3.5 years.  Results Severe, persistent PPD associated with offspring behavioral problems, low math grades and depression.  Conclusion  A large body of literature echoes the same conclusion:  PPD has noticeable, long-term effects on infant development  The more severe, more persistent the depression, the more serious the consequences Treatments for PPD  Treatments for Postpartum Depression Psychotherapy Pharmacotherapy  Interpersonal psychotherapy  Brexanolone  Individual (vs. group) therapy  Efficacy of antidepressants is equal to psychotherapy  In-home (vs. in-clinic) therapy  Antidepressants can transfer to infants through breast milk  Side effects are minimal  Some are better-studied than others Zheng et al. (2019). Psychiatry Research, 279, 83-89.; Sockol et al. (2011), Clinical Psychology Review, 31: 839-849.; Freeman et al. (2012), Current Psychiatry, 11(11), 14-21.  Interpersonal Psychotherapy (IPT)  Developed by Gerald Klerman & Myrna Weissman for major depression in the 1970’s  Dr. Margaret Spinelli recently published a manual adapting it to perinatal depression  Short-term, focused therapy lasting 12-16 weeks  Main focuses  Grief  Conflict in interpersonal relationships  Role transitions  Social isolation  IPT for Perinatal Depression  Grief  Miscarriage, stillbirth, infant with serious illness  Conflict in interpersonal relationships  Conflicts with spouse, in-laws, parents  Role transitions  Transitioning from childless to parent, career woman to fulltime caretaker  Social isolation  Helping mom build her social support network  Antidepressants for PPD  Efficacy is roughly equivalent to CBT/IPT  2011 meta-analysis suggests SSRIs have a slight advantage but studies since then have suggested the opposite  Antidepressants do make their way into breastmilk. The amount is small for SSRIs (0.4-7% of mom’s dosage), which is why they’re most often used  Minor side effects in breastfed babies can include increased crying, watery stools & sleep disturbance  Overall safety profile is good for breastfed babies  Still, 30% of breastfeeding moms refuse antidepressants Sockol et al. (2011), Clinical Psychology Review, 31: 839-849.  Depression in the menopause transition  The Menopause Transition  5 or so years leading up to the last menstrual period  Typical age of onset: 44-48 years  Hallmark: menstrual irregularity  Triggered by diminishing ovarian follicle supply Parry, B.L. (2010) Int J of Women’s Health, 2, 143-151. The Female Reproductive Lifespan Critically low levels = Menopause Transition Onset  (STRAW) The Stages of Reproductive Aging Harlow et al. (2012). JCEM, 97(4), 1159- 1168. The Menstrual Cycle  Mid-Life Alterations to the Menstrual Cycle Vanden Brink et al. (2013), Menopause, 20(12): 1243-54.; Vanden Brink et al. (2015), JCEM, 200(12), 4553-62.  Mid-Life Alterations to the Menstrual Cycle Baerwald et al. (2018), Menopause, 25(4), 399-407 Mid-Life Alterations to the Menstrual Cycle  Changes: Increase in Anovulatory Cycles Santoro et al. (2017), JCEM, 102(7), 2218-2229  Depression in the Menopause Transition  The menopause transition is associated with an increase risk of depressive symptoms1:  OR = 1.3-1.6 in the early transition  OR = 1.7-2.9 in the late transition  Increased risk of relapse in those with a history of major depression Maki et al. (2019). J Women’s Health, 28(2), 117-133. 1