I will be presenting some of the limited gender related findings, that can help us start considering relevant brain regions and connections that necessitate further direct study of gender. The 12-hour level at the first trimester of pregnancy, she has declined significantly. Here I highlight some research that has been done by colleagues in Europe. TSH and T4 and T3, to see how the thyroid is functioning with the patient who is taking lithium. For example, our team observed preliminary evidence for gender related effects of child maltreatment, physical and emotional, with adolescent girls showing more involvement of hippocampus and amygdala and frontal regions important in internalizing emotional experiences but males, more dorsal reasons subserving impulse control and externalizing behaviors and perhaps this contributes to differences that have been observed in internalizing and externalizing behaviors between girls and boys exposed to trauma. If you or a friend or family member are thinking about taking part in clinical research, this page contains basic information about clinical trials. Use these free education and outreach materials in your community and on social media to spread the word about mental health and related topics. Then, in addition, three to four of the following symptoms also need to be present: 2. little has been more meaningful to me than that with people experiencing paranoia. Not that there are some treatment resistant cases out there, which is a whole other area that needs to be studied. An important difference between mood disorders and normal mood fluctuation is: been known that bipolar disorder is . Follow NIMH on social mediaTwitter, Facebook, YouTube and LinkedIn. Skip to main content . For example, amygdala differences in adolescents and young adulthood, are among the most consistent biological findings in the disorder. As a result, what you can see, which I will highlight here with this individual participants data, that you have a 12-hour serum concentration of a woman who has taken 1200 milligrams of lithium once a day. This is the first of our series and so on June 29th,you will see the Strength in the Face of Challenge: Youth Suicide Prevention Research Among the White Mountain Apache and Navajo Nation in The Time of COVID-19. Taking a closer look at how does lamotrigine perform in patients with bipolar disorder who are pregnant. Returning to development, during adolescence and young adulthood, the epoch when bipolar disorder typically develops, frontal cortices and their white matter connections are dynamically maturing. TAMARA LEWIS JOHNSON:Great. Recently, another possible explanation has been explored in the relationship between . There are many considerations that need to be taken into account, including multiple intersecting factors so studies specifically designed to assess for gender differences and intersectionality are critically needed. Find all NIMH and cross-NIH funding opportunities. Additional research has linked factors such as lack of social support, family environment (Miklowitz, Goldstein, Neuchterlein, Snyder, & Mintz, . . This needs further study. . It has been well studied in women with epilepsy who are pregnant because there was some understanding a while ago, that actually as the woman progressed in pregnancy, her seizures were returned. to offer dynamic physiological information has become an important tool for researching brain network changes in mental disorders . When we think about perinatal mood disorders, which are thought to be more prevalent in black women in the risk of suicide in black women, we have not yet studied enough how again, how pharmacokinetics for instance, in looking at pharmacology, might help to reduce that risk for this patient population. I thank all of the viewers who stayed with us through the entire webinar. But that is exactly where I would love to take the research next, with the support of NIH, and really map out, what is the best approach, for number one, checking concentrations and being proactive about those changes when we know how significantly this drug bottoms out. . Bipolar disorder has shown important gender differences in its clinical features. What is the magnitude? Use these free digital, outreach materials in your community and on social media to spread the word about mental health. I am going to introduce our speakers, first I am going to introduce Dr. Hilary Blumberg. The prevalence of BD in the general population has been growing over the last decade, however, few epidemiological studies are available regarding BD gender distribution, leaving unanswered the question whether the often reported increment of BD diagnosis could be . HILARY PATRICIA BLUMBERG:Thank you very much for those questions. Symptoms recur with decreases in the psychotropic serum concentrations compared to a womans pre-pregnancy concentration. Estradiol rises rapidly to significant numbers during pregnancy, at least to increase cardiac output, 50 percent in fact, increased cardiac output. 2010) and has been linked to the limbic system, prefrontal cortex and ventral striatum in both primate and human studies (Beasley et al., 2011). This raises the possibility that medication and substance exposures that might increase sensitization might also increase risk of clinical features seen more in women, such as rapid cycling and mixed episodes. What we can see with the study, as clearance increases, symptoms worsen. So, just continuing, we are thinking again about the risk and benefits and that balance, discontinuation of mood stabilizers and pregnancy increases BD recurrence. I also want to make a very important point, a couple of important points about some of the neuroimaging research. So, you can see here that compared to pregnancy postpartum, her concentrations were much higher. As well as pharmacokinetics and the changes we see in perinatal women with mood stabilizers, and atypical antipsychotics, as well as where we might take future research. In one study of the cerebellar vermis, we noted higher volume only in males with bipolar disorder. There are three major points that I hope you will take away from the presentation today. Although, as Dr. Clark may discuss further, considerations have to be taken into account such as possible relationships of polycystic ovary disease and reproductive planning. Department of Health and Human ServicesUSA.gov. Dr. Blumberg, there is a question that just came in wanting to know, is the BE-SMART intervention currently available for patients? Was this because something was happening with the Lamotrigine? . I offer here some pilot data, actually, where we did just that, looking at the longitudinal perspective differences across pregnancy and postpartum in women who are taking lithium. Splitting the dose and going back to older practices, today many people take it once daily, but going back to older practices of splitting the dose can be very helpful to a pregnant woman. Consistent with emotion dysregulation as central to bipolar disorder, brain regions consistently shown to be involved in bipolar disorder are ones that subserve emotion processing and regulation, especially the amygdala and the ventral prefrontal cortex, which have substantial bidirectional inhibitory connections that are also implicated in bipolar disorder pathology. Schizophrenia (SZ) and bipolar disorder (BD) are two of the most frequent mental disorders. I would also highlight the fact that most of the participants had a variance of decreased lamotrigine clearance, as well as the variant that increased lamotrigine clearance, and it is very possible that they cancelled each other out, but we are still investigating that. Gender related effects of child maltreatment and bipolar disorder extend into adulthood. I am responsible for providing guidance and advice on matters relating to women's mental health research. Other factors associated with bipolar disorder include: trauma. With that said, acknowledgements to those who helped with the work and especially to the BIRCWH and my K23 that has helped me collect this data. Features higher in women, include depressive and mixed episodes, rapid cycling, anxiety and eating disorder comorbidities, medication resistance, and further complicating treatment, greater rates of antidepressant induced mania have been reported. She maintains an interest in trauma associated and traumatic birth as it relates to the reoccurrence of mood and anxiety symptoms in pregnancy due to past trauma and I am delighted to have both Dr. Clark and Dr. Blumberg to present today. I am not aware, I would have to look, if there has been data to look at what concentration is most likely to prevent long-term effects on the thyroid as well but definitely, this is something we are more concerned about as the patient continues their treatment and hypothyroidism in particular, is the adverse effect we are looking out for. They established several recommendations through this task force that was submitted to the Health and Human Services. When volume increases in adults are reported, often they are in males who are psychotic, and have been exposed to antipsychotic medications and lithium. But studies since then, have been unable to speak to prevalence, particularly in African American and Hispanic populations. Individuals with excessive limbic and paralimbic activity because of seizures, had symptoms similar to what is seen in bipolar disorder. Information about resources such as data, tissue, model organisms and imaging resources to support the NIMH research community. Finally, it will be critical to broaden engagement. That is related to this glomerular infiltration increase. So when we think about atypical antipsychotics, again, we are thinking about the ways in which these drugs are metabolized. A diagnosis proves you have a legitimate medical illness. Her doctor, her is a little perinatal savvy, thankfully, split her dose in pregnancy and the reason why that matters is because in pregnancy, because of the physiological changes, having a more consistent concentration across 24 hours is very important. Your research findings showed gender related effects on child maltreatment on individuals living with bipolar disorder, how can these findings inform intervention development for youth living with bipolar disorder? Participants will be muted in silent only mode and cameras will be turned off. There are many people that I would like to thank in this work. . We need to remove regulatory barriers that prohibit pregnant and nursing mothers from participating in research, and we need to leverage, establish and support new infrastructures and collaborations to perform research on pregnant and lactating women. But what about untreated bipolar disorder during pregnancy? Learn about NIMH priority areas for research and funding that have the potential to improve mental health care over the short, medium, and long term. That leads to increased glomerular infiltration rate. We have a good number of questions from the audience so I'm just going to pull directly from those. Interestingly consistent with that, recent preclinical research suggests there may be sex differences in glial gene expression in prefrontal cortex. In addition, bipolar disorder is likely to worsen with age, if the condition goes untreated. So we see this in pregnancy is not surprising. Learn Match Created by savannah_smith97 Terms in this set (127) A state of breathless euphoria, or frenzied energy, in which individuals have an exaggerated belief in their power describes: A) mania. In large scale national and international neuroimaging consortia, increased sample sizes can allow for novel comparisons between females and males. As for some people this meant that they would have increases in doses, thankfully. If so, does the data reflect the same results such as biological males to transgender females having the same issues as biological females? She is also interested in optimizing dosing of medication for mood and anxiety disorder, and other times of hormonal changes, including those related to infertility treatments and use of oral contraceptives. Concentrations are much lower compared to postpartum, where back to 80 mg dose, the concentration is much higher and in conjunction with that, seeing symptoms plummet, anxiety and depression, in particular, and they start to normalize postpartum. Studies indicate an increased risk of women in Bipolar 2 and hypomania rapid cycling, and mixed episodes, and there are important gender differences found in comorbidity. Although, even when sample sizes might have been sufficient, gender was often co-varied out and not examined as a variable of interest. Depression is by far the. You can also send an email to the email address online here, as you see on the screen. particularly pharmacotherapy for bipolar disorder. For example, we and others noted decreases in the corpus callosum and the white matter structure measure and bipolar disorder. high levels of . So we know that sexism has led to the idea that women should not be studied, they are too messy. Particularly third trimester, because that is where we expect the clearance changes, pharmacokinetic changes to be most robust. Obstructive sleep apnea (OSA) is another aspect of sleep that has been linked to mental health. That was one person. Moreover, cross sensitization with stress has long been posited as shown in the top figure. They are seven times more likely to be hospitalized for the first onset of a mood episode early postpartum. One is that the differences that we talked about are very subtle differences. . If they have a therapeutic concentration where they are feeling their best at 0.8, and then they get pregnant and that level drops to 0.5, we would anticipate that they would have a recurrence of symptoms. So here I present some pilot data that my team looked at, in terms of quetiapine, the area under the curve and oral clearance. I am going to go very quickly through references for this presentation, but I would be happy to provide them and answer any questions that you have at the end of this webinar. Dr. Clark's research interests focus on women and mood and anxiety disorders across the reproductive lifecycle. Cortical thinning is a type of mental atrophy associated with aging and linked to disorders such as dementia and . This seems to be consistent and different magnitudes across drug therapies that we commonly used for bipolar disorder. NIMH hosts an annual lecture series dedicated to innovation, invention, and scientific discovery. Dr. Blumberg also highlighted so much awesome work as it relates to imaging too, and it would be great to coordinate and collaborate with her on how we could show the changes in pharmacokinetics and how that pairs with maybe changes in the brain as well. Learn more about NIMH newsletters, public participation in grant reviews, research funding, clinical trials, the NIMH Gift Fund, and connecting with NIMH on social media. Other relatively unexplored areas of study that could be fruitful in uncovering brain gender differences in bipolar disorder, especially with new methods to study structural and functional connectivity are hemispheric lateralization and inter-hemispheric connectivity. The speakers this afternoon will highlight NIMH funded research in this area, with a focus on translational research and customizing combination therapeutic interventions for women and men who are at risk for or are living with bipolar disorder. Women with bipolar disorder are more likely to have hypothyroidism and antithyroid antibodies which have been linked to rapid cycling and, preliminary PET evidence suggests the antibodies are also related to elevated anterior singulate cortex metabolisms. Next slide please, I also wanted to make the viewers aware that our Office of Disparities Research and Workforce Diversity has several more webinars throughout the summer. Bipolar disorder and suicide Causes and triggers Treatment What is bipolar disorder? Throughout the neuroimaging work I will present, for the most part sample sizes are quite modest. Bipolar disorder, formerly called manic depression, is a mental health condition that causes extreme mood swings that include emotional highs (mania or hypomania) and lows (depression). In the review that we did of the 113 studies for suicide thoughts and behaviors, in terms of neuroimaging to try to see the brain associations, of them, we only found one study that even mentioned having someone who was transgender. Lithium has been used for more than 60 years to treat bipolar disorder . What medications have worked for her in the past? Finally, I bring you to the only study of clearance back in 1973 by Schou et al, where he looked at clearance in healthy women, not with bipolar disorder, clearance of lithium in healthy women where they took lithium for a while, 600 milligram dose, and then he looked at the clearance across 4 to 12 weeks prior to delivery and after delivery. Finally, I want to give a nod to PRGLAC, the NIH led task force on research specific to pregnant women and lactating women, which was established in 2016. What does that leave us with? People with bipolar disorder often experience episodes of mania or hypomania, depression, or a combination of both. Finally, while I presented the data on child maltreatment, I just wanted to make the point, as Dr. Clark did too, that there are many stressors that can have adverse effects over the lifespan, they change over different phases of the lifespan, and it is great that we have some data on child maltreatment, and there we need a lot more information. Special thanks to Tamara Lewis Johnson and Dr. Rudorfer, in the NIMH, for having me here today. Bipolar disorder is highly prevalent, but with similar rates in females and males, it is highly heritable, although genetic predisposition may not be the whole story in its expression. Sleep irregularities are robust risk factors and therefore important targets to prevent and reduce mood symptoms and prevent psychiatric and medical comorbidities and suicide. As well as looking at the medication and thinking about, what types of adverse effects might the woman experience or might the fetus be exposed to? TAMARA LEWIS JOHNSON:Thank you, Dr. Blumberg and Dr. Clark for outstanding presentations. So, in summary, physiological changes during pregnancy and postpartum result in pharmacokinetic changes that impact psychotropic concentration and effectiveness. This has constrained ability to perform meaningful analyses to investigate gender. Bipolar disorder is associated with early mortality, from suicide, estimated to be a preventable form of early mortality in about one in five individuals with bipolar disorder, and more women have suicidal ideation and attempts. Power is conceptually linked to BIS and BAS, particularly in social relationships . I will speak specifically to you all today about pharmacokinetics of the most commonly used agents to treat bipolar disorder and how these pharmacokinetics effect treatment and how we might think about further research to optimize management of these medications and maintain wellness. March 7, 2017. In our study we found that UGT1A4 variants *3 or L48V, which is associated with increased emotional clearance, was present in five of our participants. During the talk I have just touched briefly on pharmacological treatments, Dr. Clark will be talking more about them. So intersectionality is defined as Marginalized or disadvantaged social statuses interacting at the micro level of individuals lived experience to reflect interlocking systems of privilege and oppression at the macro social structural level, such as racism, sexism, and classism. This is particularly in the systemic perspective of pharmacokinetic studies that characterize the course of BD illness over time, to recurrence, the symptom presentation, the risk of postpartum episodes, and suicidality, if they do not have a maintained therapeutic concentration throughout pregnancy. She is the John and Hope Furth Professor of Psychiatric Neuroscience, Professor of Psychiatry, Radiology, and Biomedical Imaging in the Child Center, and the Director of the Mood Disorders Research Program at Yale School of Medicine. Higher sensitization effects in females have been shown across species, in rodents, nonhuman primates, and humans that are long-lasting and can occur from excessive catecholaminergic inputs. Learn more about research conducted at NIMH. I want to say that this webinar is sponsored by the National Institute of Mental Healths Office for Disparities research and workforce diversity. ET, M-F, Mail: National Institute of Mental Health We also know that even for women who continue their treatment, there is some recurrence. You see she has dropped a complete almost 0.7 in concentration. If you have technical difficulties hearing or viewing the webinar, please note these in the Q&A box and our technicians will work to fix the problem. Why? We have to find ways to help patients manage that. The hypothalamus has major projections to both the amygdala and ventral prefrontal cortex. When we lump the data, we see similar results as far as we can see that the changes from baseline across three trimesters of pregnancy are quite different. Though, it has connections to the amygdala and prefrontal cortex, it shows effects of lithium, and is increasingly implicated in emotional behavior. We know that women with bipolar disorder are more vulnerable during the perinatal period. Email: nimhinfo@nih.gov This afternoon we are spotlighting the research of Drs. Thank you again. Again, significantly different and significantly lower than what we see in third trimester. We really need more studies that are directly designed to address these disparities and differences and trajectories in the course of illness. Next slide. With adolescent onset, sex hormones have been implicated that could have gender related effects. This highlights the importance throughout to consider not only disadvantages of some factors that were discussing today, but also potential advantages, such as in resilience and recovery. Here we just highlight the participants in the study, who was taking 200 mg of Lamotrigine throughout her pregnancy, never changed the dose because her psychiatrist didn't think to do so, and to my knowledge, the patient was not interested doing so either, despite symptom recurrence as she got further along in pregnancy. Sleep is closely connected to mental and emotional health and has demonstrated links to depression, anxiety, bipolar disorder, and other conditions. So it is very important to give every kind of help to the youth. Such as valproic acid, which I do not use in pregnancy or in childbearing women because of the major congenital malformations that are associated with that drug. However, we recently performed a review of 113 neuroimaging studies of suicide thoughts and behaviors from the past two decades. And there is some thought that that is related to genetic differences, because it has not been related to age, race, weight, but it has not been specifically studied as it relates to age, weight, or race. These are modest studies. Pharmacokinetics of lithium in pregnancy. Such as the hippocampus, prefrontal cortex, and cerebellum. Did she need more medication? In contrast, bipolar II disorder has a prevalence rate of 0.8% in the United States and 0.3% internationally (APA, 2022) and some clinical samples suggest it is more common in women, with approximately 80-90% of individuals with rapid-cycling episodes being women (Bauer & Pfenning, 2005). TAMARA LEWIS JOHNSON:Thank you so much for responding to that question. Importantly, most studies were not designed to investigate gender effects. Though the frontal cortex has been studied a good deal in bipolar disorder, rare gender related frontal findings have been reported. Alright, so moving into addressing the gender differences particularly as it relates to this vulnerable perinatal period in the relationship to pharmacokinetics and mood stabilizers and atypical during pregnancy. However, these structures function within the context of more widely distributed brain systems that include regions that have shown preliminary evidence of gender differences in bipolar disorder. We know that too often, this has been the illness that has been misdiagnosed as schizophrenia in minority populations, especially African Americans. I will be thinking about bipolar disorder and treatment particularly through the most vulnerable time for women with bipolar disorder, that is the perinatal period. For example, stressors can vary greatly and are major risk factors for symptoms of suicide, and it is critical that we study variations in them. Hypothyroidism, including with the autoimmune cause of anti-thyroid antibodies are another mechanism that could lead to a variant cortical limbic functioning in women with bipolar disorder linked to rapid cycling. Those who are in this field and working in the specialty, already know that getting a very large sample of patients with bipolar disorder is hard. We observed evidence for an exaggeration of grey matter pruning and less increases in the structural integrity of white matter during adolescence and young adulthood in bipolar disorder. A volume decrease in specific parts of the brain's hippocampus - long identified as a hub of mood and memory processing - was linked to bipolar disorder in a study led by researchers at McGovern Medical School. I bring this back to intersectionality because it is so important to have longitudinal studies that are systematically designed to study and analyze how hypotheses that impact the specific population of investigation. You are seeing here how the concentration over a 24-hour period looked throughout the first three trimesters. If you or someone you know has a mental illness, there are ways to get help. And what are the implications on their mental health trajectory over time, with effective treatment and undertreated illness? This research was funded by NIMHs Division of Translational Research and the Division of Services and Implementation Research. We know that, in pregnancy, there are lots of physiological changes. There is a need for frequent symptom monitoring and dose adjustments are needed to maintain wellness and prevent poor outcomes. 6001 Executive Boulevard, Room 6200, MSC 9663 While it is tempting to assume that adding analysis of sex and gender to large-scale studies will be the solution, there are limitations, and the field needs to proceed with caution. These factors may also relate to Alzheimer's disease rates that are higher in women and in bipolar disorder. Just how vulnerable are they? So when we look at third trimester, it is highlighted here, looking at the second column, you can see that the clearance is 8.4, compared to late postpartum which is 3.3 liters per hour. Given the hippocampus sensitivity to stress, as well as its capabilities for plasticity, such as in response to mood stabilizing medications, there are many potential factors that can be influencing the hippocampus in bipolar disorder over the lifespan. But study of stressors has been highly limited and will be of critical importance to expand this area of research. They creatively brought together several observations. I will start with lithium because it is the gold standard and if any of my Hopkins colleagues, that is where I trained, are on the webinar today, I have to acknowledge them for their use and training of lithium because today my residents are like Im the lithium queen.
Palatka Golf Course Membership,
Dav Life Membership Benefits,
Who Is Justin Hawkins Dad,
Articles B
bipolar disorders have recently been linked to:
