Browsing by Subject "Postpartum depression"
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- ItemA “Maturational Crisis”: A Logotherapeutic Proposal for Postpartum Depression in Adolescence(2024) Moore, Mina; Le, BenjaminPostpartum depression is a complex mood disturbance that affects a significant number of mothers, exacerbating the already difficult period following childbirth. Adolescent mothers are especially vulnerable to developing postpartum depression, and in this paper I propose research of an uncommon therapeutic approach, Logotherapy, as a treatment option to combat this psychological disturbance in young mothers. Logotherapy was developed by Viktor Frankl while he was imprisoned in a Nazi Concentration Camp during the Holocaust, and it teaches that one can improve one’s mental health regardless of one’s circumstances, by finding a purpose. Logotherapy has proven to be effective in treating depression in all life stages, including adolescence, and I predict that Logotherapy would significantly reduce symptoms of postpartum depression in adolescents. Furthermore, research supports group therapy for mothers with postpartum depression, possibly due to a lack of social support as a prominent risk factor for the mood disturbance. Group Logotherapy may prove to be a useful intervention for adolescent mothers with postpartum depression.
- ItemBlocking Oxytocin Receptors in the Dorsal Raphe Nucleus of Syrian Hamsters(2019) Pisch, Natalie; Been, LauraAlmost 20% of women suffer from peripartum depression and/or anxiety which has negative ramifications for the health of both mother and baby. Despite the gravity of this public health problem, effective treatments are lacking due to an incomplete understanding of the complex neurobiological mechanisms of these conditions. Previous research suggests that the intense fluctuations of ovarian hormones that occur in pregnancy and postpartum may render women particularly vulnerable to mood disturbances in this period. In particular, changes in oxytocin signaling in the brain, mediated by estrogen and progesterone, may contribute to the etiology of peripartum depression and anxiety. Previous work from our lab found increases in oxytocin-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus and oxytocin receptors in the dorsal raphe nucleus (DRN), as well as increased anxiety-like behavior following a hormone simulated pregnancy. Given these results, this experiment sought to examine the effects of blocking oxytocin receptors in the DRN on anxiety behavior following a hormone-simulated pregnancy. Results from this pilot study suggest that blocking oxytocin signaling with an oxytocin receptor antagonist in the DRN during the postpartum period may impact anxiety-like behavior in hamsters. Further research is necessary to confirm the effects of OTA in the DRN during the peripartum period, but these results suggest that oxytocin signaling could be an important mechanism in peripartum anxiety and a potential route for the development of treatments.
- ItemDifferential Dopamine Dynamics in the Nucleus Accumbens Core and Shell during Postpartum Estrogen Withdrawal Assessed Using Fast Scan Cyclic Voltammetry(2024) Zhang, Zhongyin; Been, LauraThis thesis examines the impact of postpartum estrogen withdrawal on dopamine dynamics within the nucleus accumbens (NAc) core and shell subregions using a Hormone Simulated Pregnancy (HSP) model in mice. Utilizing Fast Scan Cyclic Voltammetry (FSCV), the study compares dopamine release and reuptake in these subregions across different hormone conditions. The results show that in the NAc core, the estrogen withdrawn group had significantly higher dopamine reuptake rates (Vmax) compared to the vehicle group, suggesting that postpartum estrogen withdrawal may increase dopamine reuptake in this subregion. Although no significant differences were found in dopamine release ([DAp]) among the treatment groups, the withdrawn group exhibited a trend towards increased [DAp] compared to the sustained and vehicle groups. In contrast, no significant differences were observed in either [DAp] or Vmax values among the treatment groups in the NAc shell. These findings suggest that hormone fluctuations during the postpartum estrogen withdrawal state have different effects on dopamine dynamics in the NAc core and shell, potentially informing novel treatments for postpartum depression (PPD). This study offers new insights into the neuroendocrinological basis of maternal behaviors and mood disorders with implications for developing therapeutic strategies targeting the dopamine system.
- ItemEffects of Ventral Tegmental Area Estrogen Receptor Alpha Knockdown Following a Hormone Simulated Pregnancy on ∆FosB production in the Nucleus Accumbens(2024) Clayton, Willow; Been, LauraThe peripartum period is characterized by extreme changes in cycling hormones such as estrogens and progesterone. During pregnancy, estradiol levels rise dramatically, but drop quickly following birth, creating an estrogen withdrawal state that is associated with changes in mood and affect in humans and rodents. The mesolimbic dopamine pathway comprises the Ventral Tegmental Area (VTA) and Nucleus Accumbens (NAc), both containing estrogen receptors. Alterations in dopamine release from the VTA to the NAc have been associated with changes in mood and affect and increased ΔFosB, a transcription factor implicated in reward and motivated behaviors, as well as that serves as a marker for long term neural plasticity. In order to better understand if and how estrogen receptors play a role in the expression of ∆FosB in the NAc following estrogen withdrawal this study used a viral mediated gene transfer approach to selectively silence ERa in the VTA. Then, following a hormone simulated pregnancy, ∆FosB was measured in the NAc using immunohistochemistry. Overall there was no significant effect of knocking down estrogen receptor alpha in the VTA on the expression of ∆FosB in the NAc following an HSP in either the estrogen withdrawn or sustained groups. Future directions will expand the number of subjects in the control groups in order to replicate past results which show a main effect of hormone condition. This would allow for a better understanding of the effects of estrogen receptor alpha knockdown on FosB expression in the VTA. Additionally, future studies, including a second part to the present study using a second cohort, will explore the possibility that estrogen receptor beta rather than alpha is required for the increased expression of ∆FosB in the NAc following an HSP.
- ItemOxytocin Receptor Plasticity Following a Hormone-Simulated Pregnancy in Syrian Hamsters: Implications for Postpartum Mood Disorders(2018) Benedetto, Lauren E.; Been, LauraDespite the fact that approximately 15‒20% of women develop postpartum depression and/or anxiety, and that the resulting outcomes for both the mother and her child are negative, the underlying neurobiological mechanisms of the disorders remain poorly understood. Previous research suggests that ovarian hormone fluctuations as well as changes in oxytocin signaling that occur at parturition and in the postpartum likely play a role in the etiology of these disorders. Given the increase in oxytocin-producing neurons in the paraventricular nucleus (PVN) of the hypothalamus following a hormone simulated pregnancy, Experiment 1 sought to examine oxytocin receptor levels in PVN efferents, particularly in the medial amygdala (MeA), nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), and raphe nuclei. Results indicate an increase in oxytocin receptor density in the raphe nuclei among hormone-withdrawn animals as compared to controls, suggesting that the region could be implicated in the etiology of anxiety-like behavior during the postpartum period. Unexpectedly, behavioral results indicate reduced non-specific locomotor ability as measured by the Open Field Test and increased anxiety-like behavior as measured by the Elevated Plus Maze in hormone-withdrawn animals. Experiment 2 sought to explore whether neurodegeneration was responsible for the decreased oxytocin-producing neurons found in hormone-sustained animals. Unexpectedly, cell death is visible in hormone-withdrawn and not hormone-sustained animals, suggesting that some neuroplasticity may be taking place. Overall, these two experiments add to our understanding of the brain and behavior following hormone-simulated pregnancy in hamsters, which may inform our understanding the postpartum period in humans.
- ItemPlasticity of Oxytocin Receptors in the Postpartum Period Using a Hamster Model(2018) Taveras, Shantal; Been, LauraThe deleterious consequences of postpartum depression and anxiety (PPD) on the mother-child dyad has greatly incentivized more research in the neurobiological mechanisms during the peripartum period. Several studies have stipulated that neurobiological and hormonal components may lead to the etiology of PPD. However, a greater understanding of the complexities of PPD will not unfold until knowledge on the typical patterns of puerperium is prioritized. In the current study, we simulated pregnancy in a hamster model to investigate changes in oxytocin receptor density in the efferents of the paraventricular nucleus (PVN). For the four regions of interest, we predicted a decrease in oxytocin receptors density for the estrogen-withdrawn hamsters within the postpartum period. The raphe nucleus (RN) was the only region of interest that attained statistical significance. Contrary to our hypothesis, the estrogen-withdrawn group exhibited a significant increase of oxytocin receptors compared to the control group in this region. Utilizing an open field test and elevated plus maze, we also expected to observe less anxiety-like behaviors from the estrogen-withdrawn group. However, our results did not reveal any statistical significance for anxiety-like behaviors. Following previous results, this study also investigated the overall neurodegeneration within the PVN, specifically an increase of cell-death in the estrogen-sustained group. After qualitative analysis, we visualized greater fluoro-jade staining, a measure of neurodegeneration, within the estrogen-withdrawn group. By gaining greater comprehension of the estrogen and oxytocin pathway, it will lead to a greater understanding of the typical postpartum period and, thereby, the intricacies involved in the peripartum period.
- ItemPostpartum Depression: A Critical Review(1999) Moore, Jennifer L.A significant number of women experience depression in the postpartum period. This article presents a review of the psychological literature on postpartum depression, including a comparison of postpartum depression to other postpartum affective disorders (maternity blues and puerperal psychosis). The biological, psychosocial, psychodynamic, and sociopolitical (feminist) etiologies of postpartum depression are explored, as well as help-seeking behaviors in women with the disorder and transcultural research on the topic. The debate about whether or not postpartum depression is a distinct diagnosis is discussed. A view of mild postpartum depression as an 'adjustment phase' to motherhood is presented, and suggestions for future research are offered.
- ItemPostpartum Oxytocin Receptor Plasticity And Anxiety-Like Behavior in Syrian Hamsters: The Potential Role of the Dorsal Raphe Nuclei(2018) Levine, Taylor; Been, LauraThe postpartum period is a time of high vulnerability for females to develop depression. Not only does postpartum depression significantly hinders the motivation and enjoyment that a mother feels in her new role, but also the development of the offspring, doubling the impact of this unique affective disorder. Oxytocin, a hormone involved in birth, maternal behavior, depression, and anxiety may help to untangle the link between postpartum hormonal levels and the occurrence of postpartum depression. The present study examined oxytocin receptor plasticity in efferents of the paraventricular nucleus, the main source of central oxytocin, in an animal model following a hormone-simulated pregnancy. Estrogen-withdrawn females exhibited a significantly greater density of oxytocin receptors in the dorsal raphe nuclei and there were no significant differences in receptor density between hormonal treatment groups in other efferents examined. Estrogen-withdrawn females also displayed higher levels of anxiety-like behavior than estrogen-sustained animals in the Elevated Plus Maze. Ultimately, the present study aimed to understand the role of oxytocin signaling in postpartum mood disturbances and how oxytocin may meet the demand as a novel, targeted treatment for postpartum depression.
- ItemPostpartum oxytocin receptor plasticity in Syrian hamsters: Implications for the treatment of peripartum mood disorders(2018) Heaton, Elizabeth C.; Been, LauraPeripartum mood disorders, if left untreated, result in negative outcomes for both the mother and child. Despite these severe consequences, the neurobiology of peripartum mood disorders is not well understood. The present study aims to build upon previous research investigating the role of oxytocin in neuroplastic and behavioral changes during the peripartum period. Past work found a significant increase in oxytocin-immunoreactive neurons in the PVN as a result of hormone withdrawal in a hormone-simulated pregnancy model conducted in Syrian hamsters. Using the same model, we studied post-synaptic plasticity: specifically, we assessed which PVN efferents, if any, experienced changes in oxytocin receptor expression using receptor autoradiography. The regions of interest in this study were medial amygdala (MA), nucleus accumbens (NA), bed nucleus of the stria terminalis (BNST), and the raphe nuclei as each of these four areas are heavily involved in the production of maternal behavior. There was a significant increase in OTR density in the dorsal raphe in the hormone withdrawn group as compared to oil control. Changes in OTR density in the dorsal RN, which regulates serotonergic activity and anxiety- and depression-related behavior in humans and rodents, may play a role in the development or sustainment of peripartum mood disorders.
- ItemThe Impact of Peripartum Estrogen Withdrawal on Dopamine Dynamics in the Nucleus Accumbens Core and Shell in Mice(2024) Courtney, May; Been, LauraThe peripartum period refers to the time before, during, and after parturition, which is the act of childbirth. Significant fluctuations in hormones occur during the peripartum period. In placental mammals, estradiol levels increase up to 100-fold during late-pregnancy and drop rapidly and immediately after parturition. This withdrawn estrogen state is believed to be involved with the neurobiological mechanisms that result in postpartum mood and anxiety disorders, which impacts roughly one in seven birthing people. Previous research has shown that estradiol withdrawal impacts the nucleus accumbens (NAc) along with motivated behaviors. However, the exact neural mechanisms that connect estradiol hormonal changes to changes in behavior are not well understood. To better understand how peripartum estrogen fluctuations impact the NAc, a hormone simulated pregnancy (HSP) was used in adult female C57BL/6 mice to model the estradiol withdrawal state and dopamine dynamics were characterized in the nucleus accumbens core (NAcC) and shell (NAcSh) using the electrochemical technique of ex-vivo fast scan cyclic voltammetry (FSCV). The results showed increased dopamine release and reuptake in the NAcC in the estrogen-withdrawn group. Dopamine release and reuptake did not vary across treatment groups in the NAcSh. Thus, these findings indicate that postpartum estrogen withdrawal does impact dopamine dynamics in the NAcC but not in the NAcSh
- ItemThe Neurobiological Etiology of Postpartum Depression: The Role of Oxytocin in the Hypothalamus and the Amygdala(2017) Bodie, Clio; Been, LauraIn the current study, we simulated the hormonal conditions of pregnancy and a postpartum period in a Syrian hamster model in order to better understand the neurobiological etiology of postpartum depression (PPD). PPD is a distinct subtype of major depressive disorder, which develops in new mothers during the first few weeks after delivery. It is a prevalent disorder and has incredibly harmful effects on both the mother and her infant, but not much is understood about its etiology, which makes treatment difficult. We hypothesized that after estrogen withdrawal produced a PPD-like state, subjects would show behavioral indicators of anhedonia through the Sucrose Preference Test. We also expected to find decreased levels of oxytocin producing cells in the paraventricular nucleus of the hypothalamus (PVN) and the medial amygdala of animals that experienced hormone withdrawal, which we believed might contribute to the development of PPD. We did not find any significant differences in the behavioral measures testing anhedonia. Our neurobiological findings were the opposite of what we hypothesized- we found significantly higher quantities of oxytocin producing neurons in the PVN of hamsters that experienced hormone withdrawal. These findings may indicate that oxytocin contributes to dysregulation of the HPA axis in the postpartum or that oxytocin fluctuations within the postpartum period affect PPD. Future research should further explore the role of oxytocin in the hypothalamus and amygdala, as it appears to be associated with PPD.
- ItemThe Neurobiological Mechanisms of Postpartum Depression: Observing Oxytocin’s Role in the Paraventricular Nucleus of the Hypothalamus Using a Hamster Model(2017) Lee, Rachel H.; Been, LauraPostpartum depression is a condition that affects new mothers’ cognition and behavior, as well as her ability to raise the child. It affects up to 15% of women who give birth and has a wide variety of symptoms. Despite its prevalence and severity, though, the neurobiological mechanisms underlying the condition remain understudied. During pregnancy and postpartum, dramatic hormone changes occur and may play a key role in the neurobiological and behavioral aspects in postpartum depression – of note is the rise in ovarian hormones followed by their sudden drop after giving birth. Current research also suggests that the dysregulation of the hormone oxytocin (OXT), which is synthesized in the paraventricular nucleus of the hypothalamus (PVH) and medial amygdala (MA), underlies the onset of postpartum depression. We modeled the postpartum hormonal changes in a hamster model, and specifically looked for changes in OXT-producing neurons in the PVH and MA using an immunohistochemical reaction. During behavioral testing, we hypothesized that hormone withdrawn animals would show a decreased preference for sugar water, and during immunohistochemistry, we hypothesized that this same group would show a significantly lower count of OXT cells, while control animals would show a significantly higher count. Interestingly, results showed the opposite of what we predicted – hormone withdrawn animals had a significantly higher count of OXT cells and vice versa. These results contain implications for potential fluctuations of OXT levels within the postpartum period itself.
- ItemThe Neurobiological Mechanisms of Postpartum Depression: The Role of Oxytocin in the Hypothalamus and Amygdala(2017) Amaral, Claudia F.; Been, LauraAlthough postpartum depression has a prevalence of approximately 15% and can result in negative outcomes for both the mother and her child, its underlying neurobiological mechanisms remain mostly unknown. Previous research suggests that ovarian hormone fluctuations that occur during the postpartum period could underlie depressive symptoms in postpartum depression. Studies have also suggested that changes in oxytocin signaling could also play a role in the etiology of this disorder. The present study adapts the ovarian withdrawal model of postpartum depression to a Syrian hamster animal model in order to study the neurobiological mechanisms of postpartum depression. Its aim is to test whether hormone withdrawal during the postpartum period results in changes in oxytocin signaling between the paraventricular nucleus and the medial amygdala. It is hypothesized that these neurobiological changes could be implicated in depressive-like behavior during the postpartum period.
- ItemThe Role of Mesolimbic Estrogen Receptors in Modulating Peripartum Estradiol Withdrawal Effects on Neuroplasticity(2024) Barrett, Annie; Been, LauraPostpartum Depression (PPD) has many biological and sociocultural contributors as well as significant implications. One biological contributor is the fluctuation in peripartum hormones, particularly the significant increase in estradiol during pregnancy, followed by a rapid decrease following childbirth, known as postpartum estradiol withdrawal. These hormone changes impact the mesolimbic dopamine pathway, which consists of dopaminergic projections from the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc). Recent evidence has shown that Estrogen Receptors (ERs) in the VTA may mediate this relationship between estradiol withdrawal and mesolimbic dopamine transmission. These changes may be measured by ΔFosB, a transcription factor in the NAc that is associated with long-term neuroplasticity and has implications for depressive-like behaviors in rodent models. We silenced ERs in the VTA using a stereotaxic injection of lentiviruses carrying short-hairpin RNA (shRNA), then we used a hormone-simulated pseudopregnancy (HSP) method to simulate the estradiol and progesterone changes during pregnancy. Finally, we used an immunohistochemistry protocol to determine the role of ERs in the VTA in modulating the effect of postpartum estradiol withdrawal on ΔFosB levels in the NAc in adult female C57BL/6 mice. We found no significant effects of the virus condition, hormone condition, or the interactions between virus and hormone conditions in the NAc Core or Shell. This study will be concluded this summer to include more scrambled control animals and a study of ESR2 knockdown. Future research would differentiate between the injected and non-injected side of the brain, and may consider interactions between ERɑ and ERβ and behavioral implications. Keywords: neuroplasticity, postpartum depression, estrogen receptors, hormone-simulated pseudopregnancy, ventral tegmental area, nucleus accumbens
- ItemΔFosB and the Nucleus Accumbens: Explanations for Peripartum Mood Disorders(2019) Valentine, Alissa; Been, LauraCurrent research fails to determine the underlying neurological explanations of peripartum mood disorder (PMD) and its many behavioral components. In particular, peripartum anxiety behavior has been found to have increased rates compared to depression-like behavior. Yet, research efforts continue to concentrate on understanding postpartum depression. This has led to a significant gap in current literature, and its inability to explain peripartum anxiety and PMD as a whole. Therefore, the present study focused on peripartum anxiety-like behavior, and its relationship with changes in nucleus accumbens (NAc) neuroplasticity, specifically the transcription factor ΔFosB. Utilizing a hormone-simulated pregnancy model, we assessed anxiety behaviors in 21 female mice using the Elevated Plus Maze and Open Field Test. Prior to behavioral testing, mice were injected with one of two viral vectors, leading either to inhibited or undisturbed ΔFosB accumulation. This allowed us to investigate how ΔFosB impacts the exhibition of peripartum anxiety. Our trends suggest that ΔFosB accumulation during pregnancy is most impactful on peripartum anxiety-like behavior, but estrogen withdrawal after delivery is more influential on the postpartum anxiety behavior phenotype. These results are the first step towards gaining a comprehensive understanding of PMD’s manifestation in the brain, and contributes to a growing body of literature supporting increased educational and diagnostic tools to respond to peripartum anxiety-related disorders.
- ItemΔFosB Induction in D1 Versus D2 Dopamine Neurons in the Nucleus Accumbens Following a Hormone-Simulated Pregnancy: An Exploratory Study(2018) Carson, Paige; Been, LauraPostpartum mood disorders (PMD) are a worldwide health concern, yet the neurobiological etiology is still widely unknown. In the present study we replicated the hormone-simulated pregnancy method developed by Liisa Galea in a novel transgenic mouse model. This approach allowed us to measure long-term genomic changes in dopaminergic plasticity in medium spiny neurons (MSNs) within the nucleus accumbens (NAc) through the transcription factor ΔFosB. We used 16 ovariectomized female transgenic mice that had fluorescent reporter molecules coupled to either D1 or D2 receptor-containing neurons; this allowed us to differentially visualize the activity of ΔFosB in each of the neuronal subtypes following a hormone-simulated pregnancy. We found a significant increase in the expression of ΔFosB in D2-MSNs in the NAc core of hormone-withdrawn animals relative to hormone-sustained animals. These neurobiological changes did not correspond with measures of anxiety in either an Elevated Plus Maze or Open Field Test. Furthermore, we found no significant changes in ΔFosB expression in D2-MSNs in the NAc shell nor in D1-MSNs in the NAc core and shell. By further understanding the influence that hormonal changes throughout pregnancy have on neurological systems, we can identify the systems that may be involved in pathological cases to develop better and more direct treatment and diagnosis options for PMD.