Materiały źródłowe

• #1 Postpartum depression: pathogenesis and treatments

  https://open.bu.edu/items/495bc935-ca6d-4313-9acc-059981bfec2a

  Postpartum depression (PPD) is a mood disorder that affects women shortly after the birth of their newborn. […] While the pathogenesis and treatment methods are similar to major depressive disorder (MDD), it is not until recently that individual research has been performed to further understand PPD and its origins as well as efficacy of treatments on mothers with their wavering biology. […] Risk factors that are statistically significant in contributing to a higher risk of PPD include biological and genetic predispositions, environmental factors such as demographics, and most importantly, the mother’s previous mental history. […] As research continues to find more effective treatments and better comprehend the biological aspect of PPD, an increased understanding of current studies may aid in the management of PPD.

• #2 Treating Postpartum Depression – Whole Health Library

  https://www.va.gov/WHOLEHEALTHLIBRARY/tools/treating-postpartum-depression.asp

  Women with postpartum depression have intense feelings of sadness, anxiety, or despair that can interfere with their ability to do their daily tasks. It can occur up to one year after having a baby, but it most commonly starts about one to three weeks after childbirth. The term postpartum depression commonly includes major and minor depression, which differ in severity and prognosis, and have a combined incidence of 12% in healthy women, who gave birth to full-term infants. […] Risk factors for postpartum depression include a history of postpartum major depression with a previous pregnancy, antenatal depressive symptoms (relative risk [RR] = 5.6), a history of major depressive disorder (RR = 4.5), poor social support (RR = 2.6), major life events or stressors during pregnancy (RR = 2.5), and a family history of postpartum major depression (RR = 2.4).

• #3 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  Postpartum depression (PPD) is a disorder that impairs the formation of the relationship between mother and child, and reduces the quality of life for affected women to a functionally significant degree. […] The purpose of this paper is to review biomarkers linked to PPD and to present selected theories on the pathogenesis of the disease based on data from biomarker studies. […] The etiopathogenesis of PPD is complex and multidirectional. As in MDD, PPD has a multicomponent pattern, in which inflammatory, hormonal, and genetic factors are attributed special roles. […] Numerous studies point to the dysregulation of the immune system during pregnancy and childbirth. […] The period of childbirth itself, associated with tremendous stress on the body, mobilization of the HPA axis, and increased inflammatory response, can be considered a causal factor in depression.

• #4 Diagnosis and Management of Postpartum Depression

  http://www.fortunejournals.com/articles/diagnosis-and-management-of-postpartum-depression.html

  The pathogenesis of postpartum depression is unknown, and to what degree the underpinnings of postpartum depression differ from those of non-perinatal depression. Factors involved in postpartum depression may include genetic susceptibility, epigenetic phenomena (e.g., DNA methylation), hormonal changes, as well as psychological and social problems and stressful life events. […] The clinical features of postpartum major depression appear comparable to those of major depressive episodes that occur outside of the postpartum period. The symptoms of postpartum major depression and major depressive episodes that occur outside of the postpartum period appear to be similar.

• #5 Biopsychosocial Models of Peripartum Depression: A Narrative Review | Revista de psicología

  https://journals.copmadrid.org/clysa/art/clysa2023a16

  Postpartum depression (PPD) is a prevalent, heterogeneous disorder with various underlying mechanisms and unwanted outcomes. Substantial uncertainty surrounding PPD aetiology exists. […] Research is ambiguous about whether PPD is distinct from depression occurring outside the peripartum period. However, there is an inclination toward the distinctiveness of PPD in the early postpartum period due to symptom severity and hormonal, genetic, and epigenetic mechanisms that differ from non-peripartum depression. […] Evidence suggests that the biological and psychosocial mechanisms of PPD are not distinct; instead, they interact together, thus supporting fundamental postulates of a biopsychosocial framework. […] A promising theoretical model to explain the pathogenesis of PPD is the general biopsychosocial model developed by George Engel in 1977.

• #6 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  This review aims to summarize the diverse proposed pathophysiological mechanisms contributing to postpartum depression, highlighting both clinical and basic science research findings. […] The evidence supporting a role for neuroendocrine changes, neuroinflammation, neurotransmitter alterations, circuit dysfunction, and the involvement of genetics and epigenetics in the pathophysiology of postpartum depression are discussed. […] This review attempts to generate a comprehensive resource for the potential underlying neurobiological mechanisms of postpartum depression, however, given the broad scope of this review, it is impossible to delve deeply into each topic. […] The peripartum period is a time of abrupt and dramatic changes in hormone levels. This period is also a vulnerable time for the development of mood disorders and it is thought that these two processes are linked in that fluctuations in reproductive hormones may play a role in the underlying neurobiology of postpartum mood disorders, a concept which has led to the ovarian-steroid-withdrawal hypothesis.

• #7 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  Dysregulation of reproductive hormones could dysregulate the levels of stress hormones thereby contributing to postpartum depression. […] The neuroactive metabolite of progesterone, allopregnanolone, has been shown to exert anxiolytic and antidepressant effects, which are thought to be mediated, at least in part, by the ability to allosterically potentiate GABAA receptors. […] Collectively, these studies begin to tell a compelling story regarding the role for allopregnanolone, GABAergic signaling, and HPA axis function in the underlying neurobiology of postpartum depression. […] The following section will focus only on studies which show a positive association between genetic variations and postpartum depression and does not include studies which were negative such as was the case for candidate gene association studies of Brain-Derived Neurotrophic Factor.

• #8 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The activity of IDO and other enzymes of the kynurenine pathway increases with placental development. […] The decreasing amount of available serotonin leads to depressive disorders. […] The study by O’Hara et al. showed lower serum estradiol levels measured in women with PPD compared to healthy women, at 36 weeks pregnant and day 2 postpartum. […] Data collected by Zonana et al. indicate that the low levels of estrogen observed after delivery may be associated with PPD, suggesting an important role of steroid hormones especially in the first days after delivery and their significance as a possible trigger for depression. […] The introduction of hormone doses at pregnancy-like level and their decrease mimicking the transition to the postpartum period resulted in the appearance of depressive symptoms, suggesting that there is a subgroup of women who are sensitive to hormonal fluctuations.

• #9 Postpartum depression – Wikipedia

  https://en.wikipedia.org/wiki/Postpartum_depression

  Estradiol levels increase during pregnancy, then drastically decrease following childbirth. When estradiol levels drop postpartum, the levels of serotonin decline as well. Serotonin is a neurotransmitter that helps regulate mood. Low serotonin levels cause feelings of depression and anxiety. Thus, when estradiol levels are low, serotonin can be low, suggesting that estradiol plays a role in the development of PPD.

• #10 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  Dysregulation of reproductive hormones could dysregulate the levels of stress hormones thereby contributing to postpartum depression. […] The neuroactive metabolite of progesterone, allopregnanolone, has been shown to exert anxiolytic and antidepressant effects, which are thought to be mediated, at least in part, by the ability to allosterically potentiate GABAA receptors. […] Collectively, these studies begin to tell a compelling story regarding the role for allopregnanolone, GABAergic signaling, and HPA axis function in the underlying neurobiology of postpartum depression. […] The following section will focus only on studies which show a positive association between genetic variations and postpartum depression and does not include studies which were negative such as was the case for candidate gene association studies of Brain-Derived Neurotrophic Factor.

• #11 A Potential End To Postpartum Depression – Texas A&M Stories

  https://today.tamu.edu/2021/10/12/a-potential-end-to-postpartum-depression/

  A drop in neurosteroid levels after childbirth leads to chemical imbalances in the brain that can cause postpartum depression. […] One specific neurosteroid, allopregnanolone, is produced in increasing amounts during pregnancy. However, after childbirth, the neurosteroid levels drop, leading to chemical imbalances in the brain that can cause postpartum depression. […] Neurosteroids, on the other hand, work immediately as antidepressants because they have a rapid mechanism of action. They enhance an already-existing receptor in the brain, so when the drug is infused, the patient immediately starts feeling better, and after the recommended three-day duration of treatment, they’ll continue to feel better for weeks. This medication helps new mothers replace their neurosteroids for the first few weeks after birth until their bodies restart production of these neurosteroids naturally.

• #12 Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions | Neuropsychopharmacology

  https://www.nature.com/articles/s41386-023-01721-1

  Preclinical and clinical studies in PPD have demonstrated the potential roles of dysfunctional GABAergic signaling, and specifically, allopregnanolone levels, in the development of PPD. […] The observation that these behavioral changes in the mice were all reversed by the administration of allopregnanolone served as compelling evidence for the development of brexanolone, a proprietary formulation of allopregnanolone. […] Brexanolone became the first Food and Drug Administration (FDA) approved treatment for PPD in human mothers, which is administered intravenously over 60 hours and has demonstrated rapid and sustained improvement in symptoms of PPD. […] There are a number of hypotheses of the underlying pathophysiology of PPD including differential sensitivity to gonadal hormonal fluctuations during pregnancy and the postpartum transition, dysregulation of the HPA axis, changes in synaptic transmission of GABA, altered levels of immune system factors, and altered neural network activity.

• #13

  https://link.springer.com/article/10.1007/s00213-023-06427-2

  This article describes the critical role of neurosteroids in postpartum depression (PPD) and outlines the landmark pharmacological journey of brexanolone as a first-in-class neurosteroid antidepressant with significant advantages over traditional antidepressants. […] The main pathology behind PPD is the postpartum reduction of neurosteroids, referred to as neurosteroid withdrawal, a concept pioneered by our preclinical studies. […] The postpartum decline of progesterone and neurosteroids after delivery, referred to as neurosteroid withdrawal, is the currently accepted etiology for PPD. […] The resulting imbalance between neurosteroid levels and GABA-A receptors may play a crucial role in PPD development. […] Neurosteroids play a key role in women’s health, with the neurosteroid, allopregnanolone (AP) being a leading compound in neurological and psychiatric studies linked to hormone alterations.

• #14 Perinatal Depression | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/27543

  Recent evidence suggests that perinatal depression is linked to the gamma-aminobutyric acid (GABA) neurotransmission system. The imbalance in GABA, the chief inhibitory neurotransmitter in the brain, likely plays a role in causing perinatal depression. […] The rapid drop in reproductive hormones, like estradiol and progesterone, following delivery can be a potential stressor in susceptible patients. These changes can lead to the onset of depressive symptoms as well as postpartum blues. […] Oxytocin and prolactin also play an essential role in the pathogenesis of perinatal depression. These hormones regulate the milk let-down reflex and the synthesis of breast milk. Failure to lactate and the onset of perinatal depression are often observed to coincide.

• #15 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  There are a number of findings that implicate HPA axis involvement in postpartum depression. […] The role of neuroendocrine factors, including HPA axis dysfunction, in postpartum depression is discussed in greater detail. […] There is evidence that the regulation of the HPA axis may be dysfunctional in women with postpartum depression, including decreased responsiveness to the dexamethasone suppression test and an altered ratio of ACTH to cortisol levels. […] The kynurenine pathway has also been implicated in postpartum depression. Increased kynurenine was associated with postpartum depression and kynurenine levels are positively associated with depression scores. […] These diverse mechanisms raise the possibility that there may be numerous mechanisms mediating the development of a common pathophysiological signature associated with postpartum depression.

• #16 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  There are a number of findings that implicate HPA axis involvement in postpartum depression. […] The role of neuroendocrine factors, including HPA axis dysfunction, in postpartum depression is discussed in greater detail. […] There is evidence that the regulation of the HPA axis may be dysfunctional in women with postpartum depression, including decreased responsiveness to the dexamethasone suppression test and an altered ratio of ACTH to cortisol levels. […] The kynurenine pathway has also been implicated in postpartum depression. Increased kynurenine was associated with postpartum depression and kynurenine levels are positively associated with depression scores. […] These diverse mechanisms raise the possibility that there may be numerous mechanisms mediating the development of a common pathophysiological signature associated with postpartum depression.

• #17 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The period of pregnancy and childbirth is subject to dysregulations of the HPA axis. […] Rapid changes in CRH concentrations as well as chronic hypercortisolism during pregnancy can be considered potential stressors. […] Elevated levels of Interleukin 1β (IL-1β) and reduced levels of BDNF were observed in rat hippocampal biopsies. […] The underlying physiological mechanism for the link between early elevated IL-1β levels in the postpartum period and the onset of depressive mood several weeks afterwards is not yet fully understood. […] The interaction effect between monoaminergic genes and environmental stressors is thought to be of great relevance to PPD susceptibility and have a possible predictive value.

• #18 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The exacerbation of rheumatoid arthritis, a Th1-dependent disease, about 3 months after delivery, indicates a long recovery period for lymphocyte subpopulations. […] The role of inflammation and the immune system as central to postpartum mood is underscored by the drug brexanolone (an analog of allopregnanolone, which in turn is a metabolite of progesterone), a modulator of the GABA-a receptor, which is thought to inhibit the inflammatory response elicited by Toll-like receptors 4 and 7 and the activity of kynurenine pathway enzymes. […] It is believed that in the case of these cells, those substances have no peripheral, but only auto and paracrine action. […] The stress of childbirth may also interfere with neuromodulation and reduce the plasticity of synapses in the hippocampus, especially since high concentrations of GCS inhibit hippocampal neuromodulation, presumably via the NMDA receptor.

• #19 Postpartum depression after adolescent stress shows a dysregulated HPA axis: a cross-species translational study – UAB News

  https://www.uab.edu/news/research-innovation/postpartum-depression-after-adolescent-stress-shows-a-dysregulated-hpa-axis-a-cross-species-translational-study

  Postpartum depression after adolescent stress shows a dysregulated HPA axis: a cross-species translational study […] Adverse life events are a known and predominant risk factor for postpartum depression in women after delivery of their baby. Furthermore, the postpartum depression in women who have experienced adverse life events tends to be refractory to treatment. […] In a study using a mouse model and human subjects, researchers from the University of Alabama at Birmingham and Johns Hopkins Medicine show that stress from adolescent social isolation in mice elicits a prolonged elevation of corticosterone levels and glucocorticoid signaling, which in turn results in long-lasting postpartum behavioral changes indicative of depression. Importantly for clinically relevant biology, this was associated with prolonged dysregulation of the neuro-hormone system that manages stress, called the hypothalamic-pituitary-adrenal, or HPA, axis.

• #20 Postpartum depression after adolescent stress shows a dysregulated HPA axis: a cross-species translational study – UAB News

  https://www.uab.edu/news/research-innovation/postpartum-depression-after-adolescent-stress-shows-a-dysregulated-hpa-axis-a-cross-species-translational-study

  Similar to the mouse results, the researchers found that childhood or adolescent stress significantly impacted HPA axis dysregulation and postpartum depression in a study of 116 women. […] Most importantly, we demonstrated that a short-term, one-week, postdelivery treatment against this pathological mechanism was sufficient to block the behavioral changes in stressed mouse dams, whereas other medicines currently used for postpartum depression in the clinical setting are ineffective, Niwa said. […] The effective treatment used a glucocorticoid receptor antagonist, a drug not currently used to treat postpartum depression. This antagonist, which blocks the effects of elevated glucocorticoids (cortisol in humans and corticosterone in rodents), could be a novel treatment option for postpartum depression. […] The novelty of this study, researchers say, lies in discovering and defining the role and mechanism of the HPA axis and glucocorticoid signaling in the context of postpartum depression.

• #21 Postpartum Depression: Overview, Risk Factors for Postpartum Mood Disorders, Screening for Postpartum Mood Disorders

  https://emedicine.medscape.com/article/271662-overview

  The initial evaluation includes a thorough medical history, physical examination, and routine laboratory tests. […] Earlier initiation of treatment is associated with a better prognosis, and the severity of the illness should guide treatment. […] Nonpharmacologic treatment strategies are useful for women with mild to moderate depressive symptoms. Individual or group psychotherapy (cognitive-behavioral and interpersonal therapy) are effective. […] Pharmacologic strategies are indicated for moderate to severe depressive symptoms or when a woman’s condition does not respond to nonpharmacologic treatment. […] The GABA system is the major inhibitory signaling pathway of the brain and CNS and contributes to regulating brain function (eg, mood, arousal, behavior, cognition). The mechanism of action for the treatment of PPD is not fully understood, but is believed to be related to positive allosteric modulation of both synaptic and extrasynaptic GABA-A receptors.

• #22 4 Targeting GABA Receptors to Treat Postpartum Depression | Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop | The National Academies Press

  https://nap.nationalacademies.org/read/26218/chapter/5

  Brexanolone, which targets GABA receptors, is the first treatment approved PPD and the first neuroactive steroid approved for a psychiatric condition (Meltzer-Brody, Zorumski). […] Although the underlying cause of PPD is not fully understood, it is likely multifactorial involving inflammatory signaling, fluctuations in perinatal hormones, dysregulation of stress pathways, and GABA signaling dysfunction, she continued. […] There had been a long-standing theory that PPD was associated with GABAergic hypo-function, providing an underlying theory that made a strong case for why it was important to investigate the impact of brexanolone in PPD patients. […] Therefore, Maguire proposed that high levels of neurosteroids during pregnancy are associated with a homeostatic downregulation of GABAA receptors to maintain an ideal level of inhibition during the pregnancy.

• #23 4 Targeting GABA Receptors to Treat Postpartum Depression | Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop | The National Academies Press

  https://nap.nationalacademies.org/read/26218/chapter/5

  When these neurosteroids begin to dramatically decrease at the time of delivery, the GABAA receptors need to be recovered to maintain an ideal level of inhibition in the postpartum period, she said. […] Deficits in the ability to recover these receptors at the time of delivery may increase the mothers vulnerability to PPD, she explained. […] She also proposed that potentiating GABAA receptors may be therapeutic for the treatment of PPD. […] Harder to explain, said Maguire, is how the action of PAMs on GABA receptors results in the persistent antidepressant effect of brexanolone seen in women with PPD. […] Inspired by this idea, Maguire and colleagues proposed that these neurosteroids may help potentiate a high level of tonic inhibition that synchronizes the neural network and mediates a transition to a more stable and a healthier network state (Pavlov et al., 2014).

• #24 4 Targeting GABA Receptors to Treat Postpartum Depression | Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop | The National Academies Press

  https://nap.nationalacademies.org/read/26218/chapter/5

  When these neurosteroids begin to dramatically decrease at the time of delivery, the GABAA receptors need to be recovered to maintain an ideal level of inhibition in the postpartum period, she said. […] Deficits in the ability to recover these receptors at the time of delivery may increase the mothers vulnerability to PPD, she explained. […] She also proposed that potentiating GABAA receptors may be therapeutic for the treatment of PPD. […] Harder to explain, said Maguire, is how the action of PAMs on GABA receptors results in the persistent antidepressant effect of brexanolone seen in women with PPD. […] Inspired by this idea, Maguire and colleagues proposed that these neurosteroids may help potentiate a high level of tonic inhibition that synchronizes the neural network and mediates a transition to a more stable and a healthier network state (Pavlov et al., 2014).

• #25 4 Targeting GABA Receptors to Treat Postpartum Depression | Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop | The National Academies Press

  https://nap.nationalacademies.org/read/26218/chapter/5

  When these neurosteroids begin to dramatically decrease at the time of delivery, the GABAA receptors need to be recovered to maintain an ideal level of inhibition in the postpartum period, she said. […] Deficits in the ability to recover these receptors at the time of delivery may increase the mothers vulnerability to PPD, she explained. […] She also proposed that potentiating GABAA receptors may be therapeutic for the treatment of PPD. […] Harder to explain, said Maguire, is how the action of PAMs on GABA receptors results in the persistent antidepressant effect of brexanolone seen in women with PPD. […] Inspired by this idea, Maguire and colleagues proposed that these neurosteroids may help potentiate a high level of tonic inhibition that synchronizes the neural network and mediates a transition to a more stable and a healthier network state (Pavlov et al., 2014).

• #26 Researchers Confirm Postpartum Depression Heritability, Home in on Treatment Mechanism | Newsroom

  https://news.unchealthcare.org/2023/10/researchers-confirm-postpartum-depression-heritability-home-in-on-treatment-mechanism/

  Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder. […] A patients PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component. […] The researchers also discovered that genetic regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA. […] Brexanolone, the only FDA-approved PPD treatment, is known to circulate throughout the body and brain. UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular brain regions. […] We view our finding as a refinement of the mechanism by which brexanolone works, Guintivano said. We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.

• #27 Researchers confirm postpartum depression heritability, home in on treatment mechanism

  https://medicalxpress.com/news/2023-10-postpartum-depression-heritability-home-treatment.html

  Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder. […] A patient’s PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component. […] The researchers also discovered that genetic regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA. […] Brexanolone, the only FDA-approved PPD treatment, is known to circulate throughout the body and brain. UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular brain regions. […] „We view our finding as a refinement of the mechanism by which brexanolone works,” Guintivano said. „We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.”

• #28 Researchers confirm postpartum depression heritability, home in on treatment mechanism | ScienceDaily

  https://www.sciencedaily.com/releases/2023/10/231019151814.htm

  Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder. […] A patient’s PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component. […] The researchers also discovered that genetic regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA. […] UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular brain regions. […] „We view our finding as a refinement of the mechanism by which brexanolone works,” Guintivano said. „We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.”

• #29 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  Postpartum depression (PPD) is a disorder that impairs the formation of the relationship between mother and child, and reduces the quality of life for affected women to a functionally significant degree. […] The purpose of this paper is to review biomarkers linked to PPD and to present selected theories on the pathogenesis of the disease based on data from biomarker studies. […] The etiopathogenesis of PPD is complex and multidirectional. As in MDD, PPD has a multicomponent pattern, in which inflammatory, hormonal, and genetic factors are attributed special roles. […] Numerous studies point to the dysregulation of the immune system during pregnancy and childbirth. […] The period of childbirth itself, associated with tremendous stress on the body, mobilization of the HPA axis, and increased inflammatory response, can be considered a causal factor in depression.

• #30 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  Postpartum depression (PPD) is a disorder that impairs the formation of the relationship between mother and child, and reduces the quality of life for affected women to a functionally significant degree. […] The purpose of this paper is to review biomarkers linked to PPD and to present selected theories on the pathogenesis of the disease based on data from biomarker studies. […] The etiopathogenesis of PPD is complex and multidirectional. As in MDD, PPD has a multicomponent pattern, in which inflammatory, hormonal, and genetic factors are attributed special roles. […] Numerous studies point to the dysregulation of the immune system during pregnancy and childbirth. […] The period of childbirth itself, associated with tremendous stress on the body, mobilization of the HPA axis, and increased inflammatory response, can be considered a causal factor in depression.

• #31 Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions | Neuropsychopharmacology

  https://www.nature.com/articles/s41386-023-01721-1

  Laboratory studies have shown that allopregnanolone inhibits inflammatory signaling through toll-like receptors (TLRs) in mouse and human macrophages and rat brain. […] This is a tremendous advancement in our understanding of why brexanolone is effective and further suggests that inflammatory signaling may contribute to the etiology of PPD. […] Our theoretical framework posits that activation of inflammatory pathways, including the production of TNF-, IL-1 and IL-6 contributes to PPD and that inhibition of the inflammatory pathways that produce these mediators contributes to clinical remission. […] Further investigation of these hypotheses may lead to a better understanding of the etiology of PPD and help clinicians determine what treatment pathways are best for their patients.

• #32 Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions | Neuropsychopharmacology

  https://www.nature.com/articles/s41386-023-01721-1

  Laboratory studies have shown that allopregnanolone inhibits inflammatory signaling through toll-like receptors (TLRs) in mouse and human macrophages and rat brain. […] This is a tremendous advancement in our understanding of why brexanolone is effective and further suggests that inflammatory signaling may contribute to the etiology of PPD. […] Our theoretical framework posits that activation of inflammatory pathways, including the production of TNF-, IL-1 and IL-6 contributes to PPD and that inhibition of the inflammatory pathways that produce these mediators contributes to clinical remission. […] Further investigation of these hypotheses may lead to a better understanding of the etiology of PPD and help clinicians determine what treatment pathways are best for their patients.

• #33 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The exacerbation of rheumatoid arthritis, a Th1-dependent disease, about 3 months after delivery, indicates a long recovery period for lymphocyte subpopulations. […] The role of inflammation and the immune system as central to postpartum mood is underscored by the drug brexanolone (an analog of allopregnanolone, which in turn is a metabolite of progesterone), a modulator of the GABA-a receptor, which is thought to inhibit the inflammatory response elicited by Toll-like receptors 4 and 7 and the activity of kynurenine pathway enzymes. […] It is believed that in the case of these cells, those substances have no peripheral, but only auto and paracrine action. […] The stress of childbirth may also interfere with neuromodulation and reduce the plasticity of synapses in the hippocampus, especially since high concentrations of GCS inhibit hippocampal neuromodulation, presumably via the NMDA receptor.

• #34 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The period of pregnancy and childbirth is subject to dysregulations of the HPA axis. […] Rapid changes in CRH concentrations as well as chronic hypercortisolism during pregnancy can be considered potential stressors. […] Elevated levels of Interleukin 1β (IL-1β) and reduced levels of BDNF were observed in rat hippocampal biopsies. […] The underlying physiological mechanism for the link between early elevated IL-1β levels in the postpartum period and the onset of depressive mood several weeks afterwards is not yet fully understood. […] The interaction effect between monoaminergic genes and environmental stressors is thought to be of great relevance to PPD susceptibility and have a possible predictive value.

• #35 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The period of pregnancy and childbirth is subject to dysregulations of the HPA axis. […] Rapid changes in CRH concentrations as well as chronic hypercortisolism during pregnancy can be considered potential stressors. […] Elevated levels of Interleukin 1β (IL-1β) and reduced levels of BDNF were observed in rat hippocampal biopsies. […] The underlying physiological mechanism for the link between early elevated IL-1β levels in the postpartum period and the onset of depressive mood several weeks afterwards is not yet fully understood. […] The interaction effect between monoaminergic genes and environmental stressors is thought to be of great relevance to PPD susceptibility and have a possible predictive value.

• #36 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  There are a number of findings that implicate HPA axis involvement in postpartum depression. […] The role of neuroendocrine factors, including HPA axis dysfunction, in postpartum depression is discussed in greater detail. […] There is evidence that the regulation of the HPA axis may be dysfunctional in women with postpartum depression, including decreased responsiveness to the dexamethasone suppression test and an altered ratio of ACTH to cortisol levels. […] The kynurenine pathway has also been implicated in postpartum depression. Increased kynurenine was associated with postpartum depression and kynurenine levels are positively associated with depression scores. […] These diverse mechanisms raise the possibility that there may be numerous mechanisms mediating the development of a common pathophysiological signature associated with postpartum depression.

• #37 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The activity of IDO and other enzymes of the kynurenine pathway increases with placental development. […] The decreasing amount of available serotonin leads to depressive disorders. […] The study by O’Hara et al. showed lower serum estradiol levels measured in women with PPD compared to healthy women, at 36 weeks pregnant and day 2 postpartum. […] Data collected by Zonana et al. indicate that the low levels of estrogen observed after delivery may be associated with PPD, suggesting an important role of steroid hormones especially in the first days after delivery and their significance as a possible trigger for depression. […] The introduction of hormone doses at pregnancy-like level and their decrease mimicking the transition to the postpartum period resulted in the appearance of depressive symptoms, suggesting that there is a subgroup of women who are sensitive to hormonal fluctuations.

• #38 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The activity of IDO and other enzymes of the kynurenine pathway increases with placental development. […] The decreasing amount of available serotonin leads to depressive disorders. […] The study by O’Hara et al. showed lower serum estradiol levels measured in women with PPD compared to healthy women, at 36 weeks pregnant and day 2 postpartum. […] Data collected by Zonana et al. indicate that the low levels of estrogen observed after delivery may be associated with PPD, suggesting an important role of steroid hormones especially in the first days after delivery and their significance as a possible trigger for depression. […] The introduction of hormone doses at pregnancy-like level and their decrease mimicking the transition to the postpartum period resulted in the appearance of depressive symptoms, suggesting that there is a subgroup of women who are sensitive to hormonal fluctuations.

• #39 Postpartum Depression: Etiology, Treatment, and Consequences for Maternal Care

  https://www.mdpi.com/2075-4418/14/9/865

  Postpartum depression (PPD) is a disabling condition that has recently shown an increase in prevalence, becoming an essential public health problem. […] Research on the genetic basis for PPD has taken place in recent years to identify the genes responsible for establishing targeted therapeutic methods and understanding its pathogenesis. […] There is evidence that biological factors, such as hormonal factors, genetics, and immune function, among other types of causes, play an essential role in triggering PPD. […] The aim of this review was to cover a broad range of issues in PPD, such as risk factors, with particular attention to ones that may be useful to identify at-risk pregnant and postpartum women; psychiatric diagnosis and biological diagnosis; clinical manifestations of PPD; genetic background associated with PPD; psychotherapy and pharmacotherapy trials, with an emphasis on therapy modifications that are specific to PPD; the use of antidepressant medication for breastfeeding mothers; the role of obstetrical–gynecologist specialists in the detection women at risk for PPD; and the public health context, with a particular emphasis on screening and management in primary care.

• #40 Postpartum Depression: Etiology, Treatment, and Consequences for Maternal Care

  https://www.mdpi.com/2075-4418/14/9/865

  The genetic risk for PPD may have a component that overlaps with the genetic risk for major depressive disorder (MDD) and/or bipolar disorder and, in addition, a component that is specific to PPD itself. Candidate gene association studies and heritability studies indicate a more substantial genetic basis when PPD occurs in the early days after birth. Further exploration of PPD-associated genes is justified and requires more extensive studies in the coming years. Ultimately, the identification of the genetic underpinnings of this disorder may bring into light the biological basis for mood disorders more generally.

• #41 Postpartum Depression: Etiology, Treatment, and Consequences for Maternal Care

  https://www.mdpi.com/2075-4418/14/9/865

  The genetic risk for PPD may have a component that overlaps with the genetic risk for major depressive disorder (MDD) and/or bipolar disorder and, in addition, a component that is specific to PPD itself. Candidate gene association studies and heritability studies indicate a more substantial genetic basis when PPD occurs in the early days after birth. Further exploration of PPD-associated genes is justified and requires more extensive studies in the coming years. Ultimately, the identification of the genetic underpinnings of this disorder may bring into light the biological basis for mood disorders more generally.

• #42 Researchers Confirm Postpartum Depression Heritability, Home in on Treatment Mechanism | Newsroom

  https://news.unchealthcare.org/2023/10/researchers-confirm-postpartum-depression-heritability-home-in-on-treatment-mechanism/

  Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder. […] A patients PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component. […] The researchers also discovered that genetic regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA. […] Brexanolone, the only FDA-approved PPD treatment, is known to circulate throughout the body and brain. UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular brain regions. […] We view our finding as a refinement of the mechanism by which brexanolone works, Guintivano said. We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.

• #43 Researchers confirm postpartum depression heritability, home in on treatment mechanism

  https://medicalxpress.com/news/2023-10-postpartum-depression-heritability-home-treatment.html

  Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder. […] A patient’s PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component. […] The researchers also discovered that genetic regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA. […] Brexanolone, the only FDA-approved PPD treatment, is known to circulate throughout the body and brain. UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular brain regions. […] „We view our finding as a refinement of the mechanism by which brexanolone works,” Guintivano said. „We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.”

• #44 Researchers confirm postpartum depression heritability, home in on treatment mechanism | ScienceDaily

  https://www.sciencedaily.com/releases/2023/10/231019151814.htm

  Postpartum depression (PPD), a common subtype of major depressive disorder, is more heritable than other psychiatric conditions, yet the genetics of PPD are understudied compared to these other psychiatric conditions, such as anxiety and bipolar disorder. […] A patient’s PPD is often not merely the result of environmental factors, such as past trauma. Instead PPD susceptibility carries a significant genetic component. […] The researchers also discovered that genetic regions involving GABAergic neurons is associated with PPD, particularly in the thalamus and hypothalamus. GABAergic neurons control the release of the neurotransmitter GABA. […] UNC researchers had discovered earlier this year that the drug worked through GABAergic neurons to treat PPD symptoms so effectively. But now, this new research suggests brexanolone likely acts on GABAergic neurons in two particular brain regions. […] „We view our finding as a refinement of the mechanism by which brexanolone works,” Guintivano said. „We now have preliminary evidence suggesting we should target GABAergic neurons in the thalamus and hypothalamus for future research.”

• #45 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  The period of pregnancy and childbirth is subject to dysregulations of the HPA axis. […] Rapid changes in CRH concentrations as well as chronic hypercortisolism during pregnancy can be considered potential stressors. […] Elevated levels of Interleukin 1β (IL-1β) and reduced levels of BDNF were observed in rat hippocampal biopsies. […] The underlying physiological mechanism for the link between early elevated IL-1β levels in the postpartum period and the onset of depressive mood several weeks afterwards is not yet fully understood. […] The interaction effect between monoaminergic genes and environmental stressors is thought to be of great relevance to PPD susceptibility and have a possible predictive value.

• #46 Postpartum and Depression Status are Associated With Lower [11C]raclopride BPND in Reproductive-Age Women | Neuropsychopharmacology

  https://www.nature.com/articles/npp2011328

  The early postpartum period is associated with increased risk for affective and psychotic disorders. Because maternal dopaminergic reward system function is altered with perinatal status, dopaminergic system dysregulation may be an important mechanism of postpartum psychiatric disorders. […] In conclusion, lower striatal D2/3 receptor BPND in postpartum and unipolar depressed women, primarily in ventral striatum, and higher dorsal striatal D2/3 receptor BPND in bipolar relative to unipolar depressives reveal a potential role for the dopamine (DA) system in the physiology of these states. […] Greater understanding of PPD neurobiology can improve nosological clarity as well as facilitate development of more effective treatments. […] We hypothesize that lower D2/3 receptor BPND in PPD relative to healthy controls given the combined contributions of increased phasic DA release of motherhood and decreased expression of D2/3 receptors due to hypercortisolemia in postpartum women.

• #47 Postpartum and Depression Status are Associated With Lower [11C]raclopride BPND in Reproductive-Age Women | Neuropsychopharmacology

  https://www.nature.com/articles/npp2011328

  The early postpartum period is associated with increased risk for affective and psychotic disorders. Because maternal dopaminergic reward system function is altered with perinatal status, dopaminergic system dysregulation may be an important mechanism of postpartum psychiatric disorders. […] In conclusion, lower striatal D2/3 receptor BPND in postpartum and unipolar depressed women, primarily in ventral striatum, and higher dorsal striatal D2/3 receptor BPND in bipolar relative to unipolar depressives reveal a potential role for the dopamine (DA) system in the physiology of these states. […] Greater understanding of PPD neurobiology can improve nosological clarity as well as facilitate development of more effective treatments. […] We hypothesize that lower D2/3 receptor BPND in PPD relative to healthy controls given the combined contributions of increased phasic DA release of motherhood and decreased expression of D2/3 receptors due to hypercortisolemia in postpartum women.

• #48 Postpartum and Depression Status are Associated With Lower [11C]raclopride BPND in Reproductive-Age Women | Neuropsychopharmacology

  https://www.nature.com/articles/npp2011328

  We posit that stress or hypercortisolemia may be a common mechanism that explains the reduction of D2/3 receptor BPND in postpartum and unipolar depressed women in this sample. […] This study provides evidence for a dopaminergic mechanism for unipolar depression in reproductive-aged women, which may provide greater rationale for DA-modifying treatments in this population.

• #49 Neurobiological Mechanism for Postpartum Depression Identified

  https://www.medscape.com/viewarticle/721584

  „During the first postpartum week, when postpartum blues tend to occur, women experience a 'dramatic’ increase in monoamine oxidase A (MAO-A) binding in key areas of the brain that affect mood, according to results of a study in the May issue of the Archives of General Psychiatry.” […] „Elevated MAO-A levels in the early postpartum period can be interpreted as a marker of a monoamine-lowering process that contributes to the mood change of postpartum blues,” Dr. Meyer and colleagues write. […] „Rather than a purely psychosocial model, they propose a 'neurobiological model of estrogen decline, followed by elevated MAO-A binding, low mood, and subsequently a period of high risk for major depressive episodes.'” […] „Given that postpartum depression is so common, maybe there is an underlying change that happens early in post partum that puts women generally at risk for depression,” Dr. Meyer said. A spike in MAO-A right after delivery, fueled by rapidly declining estrogen levels, could be one such change.

• #50 Neurobiological Mechanism for Postpartum Depression Identified

  https://www.medscape.com/viewarticle/721584

  „During the first postpartum week, when postpartum blues tend to occur, women experience a 'dramatic’ increase in monoamine oxidase A (MAO-A) binding in key areas of the brain that affect mood, according to results of a study in the May issue of the Archives of General Psychiatry.” […] „Elevated MAO-A levels in the early postpartum period can be interpreted as a marker of a monoamine-lowering process that contributes to the mood change of postpartum blues,” Dr. Meyer and colleagues write. […] „Rather than a purely psychosocial model, they propose a 'neurobiological model of estrogen decline, followed by elevated MAO-A binding, low mood, and subsequently a period of high risk for major depressive episodes.'” […] „Given that postpartum depression is so common, maybe there is an underlying change that happens early in post partum that puts women generally at risk for depression,” Dr. Meyer said. A spike in MAO-A right after delivery, fueled by rapidly declining estrogen levels, could be one such change.

• #51 Neurobiological Mechanism for Postpartum Depression Identified

  https://www.medscape.com/viewarticle/721584

  „During the first postpartum week, when postpartum blues tend to occur, women experience a 'dramatic’ increase in monoamine oxidase A (MAO-A) binding in key areas of the brain that affect mood, according to results of a study in the May issue of the Archives of General Psychiatry.” […] „Elevated MAO-A levels in the early postpartum period can be interpreted as a marker of a monoamine-lowering process that contributes to the mood change of postpartum blues,” Dr. Meyer and colleagues write. […] „Rather than a purely psychosocial model, they propose a 'neurobiological model of estrogen decline, followed by elevated MAO-A binding, low mood, and subsequently a period of high risk for major depressive episodes.'” […] „Given that postpartum depression is so common, maybe there is an underlying change that happens early in post partum that puts women generally at risk for depression,” Dr. Meyer said. A spike in MAO-A right after delivery, fueled by rapidly declining estrogen levels, could be one such change.

• #52 Neurobiological Mechanism for Postpartum Depression Identified

  https://www.medscape.com/viewarticle/721584

  „During the first postpartum week, when postpartum blues tend to occur, women experience a 'dramatic’ increase in monoamine oxidase A (MAO-A) binding in key areas of the brain that affect mood, according to results of a study in the May issue of the Archives of General Psychiatry.” […] „Elevated MAO-A levels in the early postpartum period can be interpreted as a marker of a monoamine-lowering process that contributes to the mood change of postpartum blues,” Dr. Meyer and colleagues write. […] „Rather than a purely psychosocial model, they propose a 'neurobiological model of estrogen decline, followed by elevated MAO-A binding, low mood, and subsequently a period of high risk for major depressive episodes.'” […] „Given that postpartum depression is so common, maybe there is an underlying change that happens early in post partum that puts women generally at risk for depression,” Dr. Meyer said. A spike in MAO-A right after delivery, fueled by rapidly declining estrogen levels, could be one such change.

• #53 The role of reproductive hormones in postpartum depression | CNS Spectrums | Cambridge Core

  https://www.cambridge.org/core/journals/cns-spectrums/article/role-of-reproductive-hormones-in-postpartum-depression/AC701DEB8CE0A817B0F68C9BC33A532D

  Despite decades of research aimed at identifying the causes of postpartum depression (PPD), PPD remains common, and the causes are poorly understood. […] Many have attributed the onset of PPD to the rapid perinatal change in reproductive hormones. […] Although a number of human and nonhuman animal studies support the role of reproductive hormones in PPD, several studies have failed to detect an association between hormone concentrations and PPD. […] We discuss and integrate the literature on animal models of PPD and human studies of reproductive hormones and PPD. […] Reproductive hormones influence virtually every biological system implicated in PPD, and a subgroup of women seem to be particularly sensitive to the effects of perinatal changes in hormone levels. […] We propose that these women constitute a hormone-sensitive PPD phenotype, which should be studied independent of other PPD phenotypes to identify underlying pathophysiology and develop novel treatment targets.

• #54 Causal mechanisms of postnatal depression among women in Gondar town, Ethiopia: application of a stress-process model with generalized structural equation modeling | Reproductive Health | Full Text

  https://reproductive-health-journal.biomedcentral.com/articles/10.1186/s12978-020-00912-z

  A CMD before pregnancy and low birth weight (LBW) increased PND scores, and these effects were in part mediated via antenatal depression and labor complications. […] Understanding the potential mechanisms by which stresses can lead to depression is now considered essential to enable the development of preventative PND interventions. […] The stress process model consists of three main conceptual domains. The first domain consists of a source of stress (stressor) domain, which includes life events and chronic life strains. The second domain consists of the mediators domain, which includes any mediators of stress that have an ability to mediate the impact of stressful situations such as social support and coping styles from the stressor. The third domain consists of the stress outcome, which is a manifestation of the stress of various mental disorders. […]

• #55 Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions | Neuropsychopharmacology

  https://www.nature.com/articles/s41386-023-01721-1

  Preclinical and clinical studies in PPD have demonstrated the potential roles of dysfunctional GABAergic signaling, and specifically, allopregnanolone levels, in the development of PPD. […] The observation that these behavioral changes in the mice were all reversed by the administration of allopregnanolone served as compelling evidence for the development of brexanolone, a proprietary formulation of allopregnanolone. […] Brexanolone became the first Food and Drug Administration (FDA) approved treatment for PPD in human mothers, which is administered intravenously over 60 hours and has demonstrated rapid and sustained improvement in symptoms of PPD. […] There are a number of hypotheses of the underlying pathophysiology of PPD including differential sensitivity to gonadal hormonal fluctuations during pregnancy and the postpartum transition, dysregulation of the HPA axis, changes in synaptic transmission of GABA, altered levels of immune system factors, and altered neural network activity.

• #56 Mechanism of Drug for Postpartum Depression Revealed | Technology Networks

  https://www.technologynetworks.com/drug-discovery/news/mechanism-of-drug-for-postpartum-depression-revealed-370416

  Post-partum depression (PPD) develops after childbirth and affects both the mothers and the infants health by preventing healthy bonding. […] A research team led by A. Leslie Morrow, PhD, the John Andrews Distinguished Professor of Psychiatry and Pharmacology in the UNC School of Medicine, has found that brexanolone works within the body by inhibiting the key systemic inflammatory pathways that are associated with depression. The new finding is monumental in that it suggests that PPD is likely caused, at least in part, by inflammation. […] The research suggests that the therapeutic effects of brexanolone are likely brought on by its ability to inhibit toll-like receptor pathways and reduce inflammatory markers. The same inflammatory markers have been shown to be up-regulated in PPD, which means that inflammation may be at least partially responsible for the condition. […] But recent data and this new study suggest that inflammation may be contributing to the syndrome.

• #57 FDA Approves New Postpartum Depression Treatment – NewYork-Presbyterian – Psychiatry, Women’s Health

  https://healthmatters.nyp.org/fda-approves-new-postpartum-depression-treatment/

  Postpartum depression is a serious but common condition, affecting about 1 in 8 women, according to the Centers for Disease Control and Prevention. […] Zuranolone is a synthetic form of allopregnanolone, a metabolite of progesterone, that rises greatly across pregnancy and has a calming effect on the brain. […] Numerous studies have identified that dysregulation in this system both shifts in the levels of allopregnanolone and changes in the conformation of the receptor may play an important role in postpartum depression. […] While zuranolone itself is a new medication, it mimics a hormone that is natural in the body and works through a mechanism that we know to be implicated in postpartum depression from many years of basic scientific research. […] There is tremendous excitement about the possibility of zuranolone because it is working off this mechanism that is so specific to the postpartum period and to this distinct condition.

• #58 Postpartum depression after adolescent stress shows a dysregulated HPA axis: a cross-species translational study – UAB News

  https://www.uab.edu/news/research-innovation/postpartum-depression-after-adolescent-stress-shows-a-dysregulated-hpa-axis-a-cross-species-translational-study

  Similar to the mouse results, the researchers found that childhood or adolescent stress significantly impacted HPA axis dysregulation and postpartum depression in a study of 116 women. […] Most importantly, we demonstrated that a short-term, one-week, postdelivery treatment against this pathological mechanism was sufficient to block the behavioral changes in stressed mouse dams, whereas other medicines currently used for postpartum depression in the clinical setting are ineffective, Niwa said. […] The effective treatment used a glucocorticoid receptor antagonist, a drug not currently used to treat postpartum depression. This antagonist, which blocks the effects of elevated glucocorticoids (cortisol in humans and corticosterone in rodents), could be a novel treatment option for postpartum depression. […] The novelty of this study, researchers say, lies in discovering and defining the role and mechanism of the HPA axis and glucocorticoid signaling in the context of postpartum depression.

• #59 Postpartum Depression, Neurotransmitters, And Nutrition

  https://www.mentalhealth.com/library/postpartum-depression-neurotransmitters-and-nutrition

  Like other forms of depression, postpartum depression (PPD) is often associated with a neurotransmitter imbalance. Many new mothers with PPD have low serotonin or norepinephrine levels in the brain that are aggravated by nutritional deficiencies. Scientists have found that proper nutrition is essential for the production of neurotransmitters. […] As research examines the role of serotonin in regulating mood, low serotonin levels have been associated with virtually every type of depression. Serotonin and its group of neurotransmitters called catecholamines are chiefly made by the adrenal glands. They all work together to stabilize our moods. When the stress in our life increases, our adrenal glands make more catecholamines, which in turn causes our brains have less serotonin to maintain balance. As stressful events like pregnancy and childbirth occur, the brain can struggle to make enough serotonin to meet the new levels of catecholamines.

• #60 Postpartum Depression, Neurotransmitters, And Nutrition

  https://www.mentalhealth.com/library/postpartum-depression-neurotransmitters-and-nutrition

  The production of serotonin is a complex process that requires specific nutrients. In order to convert tryptophan into 5-hydroxy-L-tryptophan (5-HTP), the body needs sufficient iron and vitamin B3 (niacin). Additionally, the body needs other B vitamins and magnesium to convert vitamin B6 to pyridoxyl-5-phosphate (P5P). If someone does not have enough 5-HTP and P5P, the brain will not produce sufficient serotonin, resulting in depression. […] When the brain receives the correct levels of nutrients, it functions properly, reducing a woman’s chances of developing PPD or other forms of depression. Research has found a number of dietary changes that help alleviate depression. The Mediterranean diet is effective in combating the health problems associated with mood disorders. In addition to reducing depression in new mothers, the Mediterranean diet has been found to have health benefits for their children as well.

• #61 Postpartum Depression, Neurotransmitters, And Nutrition

  https://www.mentalhealth.com/library/postpartum-depression-neurotransmitters-and-nutrition

  Other research has found an association between low fatty acids levels and the occurrence of PPD, indicating that pregnant women might be able to lower their risk of becoming depressed before and after giving childbirth by eating more fish. Some scientists have suggested that the relatively high incidence of PPD in the United States may be triggered by a low dietary intake of DHA. One study compared prevalence rates for PPD with the DHA content in mothers’ milk and seafood consumption rates in studies from 23 countries. The results indicated that lower prevalence rates of PPD were significantly associated with high concentrations of DHA in mothers’ milk and greater seafood consumption. […] For new mothers who are nursing and do not want to take medication, nutrition and dietary changes may represent viable alternatives. In addition to therapy and other alternative therapies, nutrition counseling can be helpful in relieving depressive symptoms and improving overall well-being.

• #62 Treating Postpartum Depression – Whole Health Library

  https://www.va.gov/WHOLEHEALTHLIBRARY/tools/treating-postpartum-depression.asp

  Dietary supplementation with omega-3 fats prenatally may decrease the risk of developing postpartum depression, as well as reduce some depressive symptoms in the postpartum period. […] Studies suggest a link between low serum vitamin D levels and an increased risk of postpartum depression. […] Correction of vitamin D deficiency may play a significant role in the recovery from postpartum depression. […] Movement is one of the most important, low-cost, and effective treatments for depression. The available research on physical activity and yoga as interventions for perinatal depression is encouraging with regard to feasibility, acceptability, patient safety, and preliminary efficacy.

• #63 Treating Postpartum Depression – Whole Health Library

  https://www.va.gov/WHOLEHEALTHLIBRARY/tools/treating-postpartum-depression.asp

  Dietary supplementation with omega-3 fats prenatally may decrease the risk of developing postpartum depression, as well as reduce some depressive symptoms in the postpartum period. […] Studies suggest a link between low serum vitamin D levels and an increased risk of postpartum depression. […] Correction of vitamin D deficiency may play a significant role in the recovery from postpartum depression. […] Movement is one of the most important, low-cost, and effective treatments for depression. The available research on physical activity and yoga as interventions for perinatal depression is encouraging with regard to feasibility, acceptability, patient safety, and preliminary efficacy.

• #64 Biomarkers of Postpartum Depression: A Narrative Review

  https://www.mdpi.com/2077-0383/12/20/6519

  Postpartum depression (PPD) is a disorder that impairs the formation of the relationship between mother and child, and reduces the quality of life for affected women to a functionally significant degree. […] The purpose of this paper is to review biomarkers linked to PPD and to present selected theories on the pathogenesis of the disease based on data from biomarker studies. […] The etiopathogenesis of PPD is complex and multidirectional. As in MDD, PPD has a multicomponent pattern, in which inflammatory, hormonal, and genetic factors are attributed special roles. […] Numerous studies point to the dysregulation of the immune system during pregnancy and childbirth. […] The period of childbirth itself, associated with tremendous stress on the body, mobilization of the HPA axis, and increased inflammatory response, can be considered a causal factor in depression.

• #65 Pathophysiological Mechanisms Implicated in Postpartum Depression

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6370514/

  There are a number of findings that implicate HPA axis involvement in postpartum depression. […] The role of neuroendocrine factors, including HPA axis dysfunction, in postpartum depression is discussed in greater detail. […] There is evidence that the regulation of the HPA axis may be dysfunctional in women with postpartum depression, including decreased responsiveness to the dexamethasone suppression test and an altered ratio of ACTH to cortisol levels. […] The kynurenine pathway has also been implicated in postpartum depression. Increased kynurenine was associated with postpartum depression and kynurenine levels are positively associated with depression scores. […] These diverse mechanisms raise the possibility that there may be numerous mechanisms mediating the development of a common pathophysiological signature associated with postpartum depression.

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