Review
Biochemistry & Molecular Biology
Carmen J. Zamora-Sanchez, Ignacio Camacho-Arroyo
Summary: Allopregnanolone is a extensively studied progesterone metabolite and its synthetic analogs are evaluated as therapeutic agents for anxiety and depression. Recent research has shown that 3 alpha-THP has dual-regulatory effects on the development of certain cancers. This review explores the metabolism and mechanisms of action of 3 alpha-THP in both normal and tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Sara Carlini, Lauren M. Osborne, Kristina M. Deligiannidis
Summary: Postpartum depression has negative effects on childbearing persons globally. Current treatments have limited evidence, while hormonal treatments have rationality but limited efficacy. In contrast, the development of antidepressants with allopregnanolone analogues has shown promise.
DIALOGUES IN CLINICAL NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Semra Etyemez, Kristen N. Miller, Kristin M. Voegtline, Ipek Ozdemir, Lindsay R. Standeven, Luca Spiro Santovito, Graziano Pinna, Jennifer L. Payne, Lauren M. Osborne
Summary: Anxiety disorders during the perinatal period are common and can increase the risk of postpartum depression. However, little is known about the biological factors in perinatal anxiety. This study aims to explore the relationship between anxiety without comorbid depression and the metabolic pathways of neuroactive steroids (NAS) in pregnant women.
PSYCHONEUROENDOCRINOLOGY
(2023)
Review
Endocrinology & Metabolism
Peter M. Lambert, Xinguo Lu, Charles F. Zorumski, Steven Mennerick
Summary: The rise of ketamine and brexanolone as rapid antidepressant treatments has prompted research into their common mechanisms. These drugs have distinct characteristics compared to traditional antidepressants in terms of onset time and duration of effect. Based on existing studies, network disinhibition and increased high-frequency oscillations are potential mechanisms underlying the acute effects of rapid antidepressants.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Medicine, Research & Experimental
Thiraphat Saengmearnuparp, Bannakij Lojanapiwat, Nipon Chattipakorn, Siriporn Chattipakorn
Summary: Recent literature has linked 5-alpha reductase inhibitors (5-ARIs) with neuropsychiatric adverse effects, with former users showing a higher incidence of depressive symptoms. The mechanisms behind this association, known as post finasteride syndrome (PFS), are not yet fully understood. Possible mechanisms include alterations in neuroactive steroids, dopaminergic dysfunction, reduced hippocampal neurogenesis, increased neuroinflammation, alterations in the HPA axis, and epigenetic modifications.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Immunology
Shibani S. Mukerji, Vikas Misra, David R. Lorenz, Sukrutha Chettimada, Kiana Keller, Scott Letendre, Ronald J. Ellis, Susan Morgello, Robert A. Parker, Dana Gabuzda
Summary: This study found that in HIV-infected individuals receiving ART, depressive symptoms were associated with lower levels of neuroactive steroids, suggesting altered neuroactive steroid metabolism may contribute to the pathophysiological mechanisms of depression.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Behavioral Sciences
Douglas F. Covey, Alex S. Evers, Yukitoshi Izumi, Jamie L. Maguire, Steven J. Mennerick, Charles F. Zorumski
Summary: Endogenous neurosteroids and synthetic neuroactive steroids are significant targets for therapeutic development in neuropsychiatric disorders. Studies on unnatural enantiomers of key neurosteroids have provided insights into the interactions of synthetic steroids with receptors, ion channels, and intracellular sites of action. The effects of these enantiomers suggest that they may have therapeutic potential that complements or exceeds their natural counterparts.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Rok Cerne, Arnold Lippa, Michael M. Poe, Jodi L. Smith, Xiaoming Jin, Xingjie Ping, Lalit K. Golani, James M. Cook, JeffreyM. Witkina
Summary: Positive allosteric modulators of GABAA receptors, known as GABAkines, have been widely used for treating anxiety, epilepsy, sleep disorders, and other conditions for over 70 years. However, traditional GABAkines like diazepam have safety and tolerability concerns. While there are several new GABAkines in development, the issue of side effects has not been fully resolved. Therefore, further research and improvement of GABAkines remain important in the field.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Neurosciences
Najah L. Walton, Pantelis Antonoudiou, Lea Barros, Tauryn Dargan, Alyssa DiLeo, Aidan Evans-Strong, Jenah Gabby, Samantha Howard, Rumzah Paracha, Edgardo J. Sanchez, Grant L. Weiss, Dong Kong, Jamie L. Maguire
Summary: Chronic stress is a major risk factor for psychiatric illnesses, including depression. Allopregnanolone, an important neurosteroid, is found to be reduced under chronic stress, leading to behavioral deficits. Targeting allopregnanolone may offer a novel therapeutic strategy for mood disorders.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Behavioral Sciences
Liisa Hantsoo, Jennifer L. Payne
Summary: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder that is associated with hormonal fluctuations, and its underlying biology is not yet fully understood. Recent research suggests that abnormal central nervous system response to neuroactive steroid hormone fluctuations, alterations in serotonergic and GABA transmission, genetic heritability, and cellular vulnerability to sex hormones may contribute to PMDD. However, the findings have not yet been integrated into a complete description of PMDD's underlying biology, and a subtyping approach may be beneficial for future research.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Psychiatry
Jemma E. Cook, Donna M. Platt, Daniela Ruedi-Bettschen, James K. Rowlett
Summary: Combining benzodiazepines and neuroactive steroids can lead to supra-additive anxiolytic effects and infra-additive reinforcing effects in male rhesus monkeys, indicating an improved therapeutic window. However, the results are inconsistent in female rhesus monkeys, with three monkeys showing supra-additive reinforcing effects and one monkey showing infra-additive reinforcing effects. Furthermore, both benzodiazepines and neuroactive steroids significantly increased deep sedation and observable ataxia.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Behavioral Sciences
Gabriele Floris, Gino Paolo Asuni, Giuseppe Talani, Francesca Biggio, Maria Giuseppina Pisu, Mary Tresa Zanda, Liliana Contu, Elisabetta Maciocco, Mariangela Serra, Paolo Follesa
Summary: This study investigates the role of the GABA(B)R receptor in alcohol consumption and preference in mice. The results show that mice lacking functional GABA(B)R drink more alcohol, prefer alcohol over water, and have higher blood alcohol concentrations compared to wild-type mice. Additionally, the study suggests that the GABA(B)R receptor modulates the activity of GABA(A) receptors in the hippocampus, potentially influencing alcohol preference in mice.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Michal Kaleta, Jana Oklestkova, Ondrej Novak, Miroslav Strnad
Summary: Neuroactive steroids are a family of compounds that can affect nervous system functions, synthesized in either the nervous system or peripheral endocrine tissues. Monitoring the production and levels of neuroactive steroids can be beneficial for the prevention, diagnosis, monitoring, and treatment of neurodegenerative and psychiatric diseases. Immunoanalytical methods and chromatography combined with mass spectrometry are highlighted as relevant techniques for analyzing neuroactive steroids.
Article
Pharmacology & Pharmacy
Eva Dolejsi, Nikolai Chetverikov, Eszter Szanti-Pinter, Dominik Nelic, Alena Randakova, Vladimir Dolezal, Esam E. El-Fakahany, Eva Kudova, Jan Jakubik
Summary: Endogenous neurosteroids and their synthetic analogues, known as neuroactive steroids, bind to muscarinic acetylcholine receptors and modulate acetylcholine binding and function. Radioligand binding experiments show that neuroactive steroids bind to two different affinity sites on the receptors, with each site having a unique binding profile compared to other allosteric modulators. Additionally, membrane cholesterol competes with neurosteroids/neuroactive steroids binding, indicating that both binding sites are oriented towards the cell membrane.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ajna Hamidovic, John Davis, Fatimata Soumare, Avisek Datta, Aamina Naveed
Summary: This study examined the variations of allopregnanolone, a neuroactive steroid, and its ratio to progesterone across different subphases of the menstrual cycle. The findings showed that allopregnanolone levels were highest during the mid-luteal phase and the ratio of allopregnanolone to progesterone was lowest during this phase. These results highlight the hormonal changes that occur during the menstrual cycle.
Article
Public, Environmental & Occupational Health
Liisa Hantsoo, Husna Sajid, Laura Murphy, Brett Buchert, Jordan Barone, Sabina Raja, Tory Eisenlohr-Moul
Summary: This study aimed to examine patients' experiences with different health care specialties when seeking care for PMDD symptoms, finding that different providers have different strengths in assessing and treating PMDD. Patients reported varied interactions and experiences with different medical professionals, highlighting the importance of tailored care for individuals with PMDD.
JOURNAL OF WOMENS HEALTH
(2022)
Article
Psychiatry
Elizabeth S. Wenzel, Tory Eisenlohr-Moul, Unnathi Nagelli, Beatriz Penalver Bernabe, Pauline M. Maki
Summary: Perinatal depression affects 6.5-12.9% of women, with high rates in women of color and comorbid perinatal anxiety in up to 50% of cases. The Research Domain Criteria (RDoC) provides a translational framework for identifying transdiagnostic psychiatric symptoms, but its application in perinatal affective disorders (PNAD) is yet limited. This study identified RDoC-based transdiagnostic features of PNAD and found that potential threat may be a prominent, transdiagnostic feature of perinatal anxiety and depression, whereas reward valuation may be a non-transdiagnostic, weaker feature of perinatal depression.
ARCHIVES OF WOMENS MENTAL HEALTH
(2022)
Article
Psychology, Biological
Annie K. Griffith, Michelle M. Martel, Tory Eisenlohr-Moul, Mark T. Fillmore
Summary: Compared with men, women are more affected by alcohol, and the fluctuation of ovarian hormones and reduced inhibitory control may contribute to this vulnerability. This study found that the disinhibiting effect of alcohol increased nearly twofold during the late follicular phase, suggesting that ovarian hormone fluctuations play a role in increasing the risk of excessive alcohol use in women.
EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
(2023)
Article
Substance Abuse
Jordan C. C. Barone, Jaclyn M. M. Ross, Anisha Nagpal, Gabriela Guzman, Erin Berenz, Raina D. D. Pang, Tory A. A. Eisenlohr-Moul
Summary: This study examines the relationship between alcohol use and drinking motives across the menstrual cycle in female psychiatric outpatients. The results show that women are more likely to drink heavily on weekends during the periovulatory and perimenstrual phases, and they are more likely to drink to cope during the perimenstrual phase. These findings highlight the predictable phases of increased high-risk alcohol use and the importance of individual assessment of cyclical changes to prevent heavy drinking during ovulation and menstruation.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Article
Psychiatry
Beatriz Penalver Bernabe, Pauline M. Maki, Janet L. Cunningham, Tory Eisenlohr-Moul, Lisa Tussing-Humphreys, Ian M. Carroll, Samantha Meltzer-Brody, Jack A. Gilbert, Mary Kimmel
Summary: Higher stress during pregnancy is associated with negative outcomes and elevated inflammation. The gut microbiota and host immune responses provide insights into perceived stress during pregnancy. This study examined the associations between perceived stress, gut microbiota composition, and immune system activity in two cohorts of pregnant individuals. The results showed distinct taxonomical and immunological signatures related to perceived stress, suggesting the potential role of the gut microbiome and immune factors in modulating stress during pregnancy.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Psychology, Clinical
Ashley G. Eng, Jenny M. Phan, Elizabeth A. Shirtcliff, Tory A. Eisenlohr-Moul, Patrick K. Goh, Michelle M. Martel
Summary: The reproductive neuroendocrine system may explain why some ADHD youths experience worsened symptoms during adolescence. This study found that males with ADHD had higher levels of hyperactivity, impulsivity, and inattention, while females had higher levels of impairment. As youth aged, hyperactivity and impulsivity declined, while impairment and depressive symptoms increased, especially amongst those at later pubertal stages.
RESEARCH ON CHILD AND ADOLESCENT PSYCHOPATHOLOGY
(2023)
Article
Urology & Nephrology
Jeff Kiesner, Celeste Bittoni, Tory Eisenlohr-Moul, Barry Komisaruk, Massimiliano Pastore
Summary: This study aims to examine the association between the menstrual cycle and changes in sexual desire, taking into account psychological and physical changes. Analysis of daily reports from 213 female university students over 2 menstrual cycles showed individual differences in how the menstrual cycle influences sexual desire. Results also highlight the importance of psychological changes for predicting sexual desire.
JOURNAL OF SEXUAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Melissa J. M. Walsh, Kathryn Gibson, Megan Hynd, Tory A. Eisenlohr-Moul, Erin C. Walsh, Lauren Schiff, Fred Jarskog, David Lalush, Gabriel S. Dichter, Crystal E. Schiller
Summary: This clinical trial aims to investigate the neural and molecular mechanisms by which estradiol treatment improves symptoms of anhedonia and psychosis during the perimenopausal transition. The study will recruit 100 unmedicated women in the late-stage perimenopausal transition and assess clinical symptoms and neurobiological markers before and after estradiol treatment. This research will provide valuable insights into predicting, treating, and developing biomarkers for perimenopausal psychiatric symptoms.
Article
Psychology, Developmental
Elizabeth Andersen, Hannah Klusmann, Tory Eisenlohr-Moul, Kayla Baresich, Susan Girdler
Summary: Female adolescents are at increased risk of depression during puberty, and this risk continues throughout their reproductive lifespan. Hormone fluctuation is considered a key factor in the development of mood disorders tied to reproductive events, but its effects on affective state change during puberty are not well understood. This study investigated the impact of recent stressful life events on the relationship between hormone change and affective symptoms in peripubertal females. The results showed that stressful life events near the pubertal transition influenced the effects of hormone change on affective symptoms, with greater symptoms associated with hormone increases in a high stress context and hormone decreases in a low stress context. These findings suggest that stress-related hormone sensitivity may contribute to the development of affective symptoms during peripubertal hormone flux.
DEVELOPMENT AND PSYCHOPATHOLOGY
(2023)
Editorial Material
Neurosciences
Tory A. Eisenlohr-Moul, Jordan C. Barone
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Tory Eisenlohr-Moul, Danielle A. Swales, David R. Rubinow, Lauren Schiff, Crystal E. Schiller
Summary: The hormonal changes during pregnancy and childbirth can affect a person's emotional state, especially for those with a history of postpartum depression. This study aimed to understand how hormone-sensitive individuals can be differentiated from hormone-insensitive controls and which symptoms show the most rapid and consistent response. The results showed that hormone-sensitive participants could be distinguished from controls early on in the study, with symptoms such as anger/irritability, mood swings, and fatigue showing the most significant changes within the first week of hormone manipulation. This study highlights the importance of reproductive hormones in perinatal affective disorders and suggests that anger and irritability may be early indicators of hormone sensitivity.
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Neurosciences
Jordan Barone, Jessica Peters, Tory Eisenlohr-Moul
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Jordan Barone, A. Leslie Morrow, David Rubinow, Susan Girdler, Tory Eisenlohr-Moul
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Jordan Barone, Tory Eisenlohr-Moul
BIOLOGICAL PSYCHIATRY
(2022)
Meeting Abstract
Neurosciences
Tory Eisenlohr-Moul, Daniel Moriarity
BIOLOGICAL PSYCHIATRY
(2022)
Article
Endocrinology & Metabolism
Shanshan Xiao, Natalie C. Ebner, Amirhossein Manzouri, Tie-Qiang Li, Diana S. Cortes, Kristoffer N. T. Mansson, Hakan Fischer
Summary: The mechanisms through which intranasal oxytocin affects the brain are not fully understood, but recent research suggests that brain regions with a higher density of oxytocin receptors may play a key role. This study used resting-state fMRI to investigate the effects of intranasal oxytocin administration on connectivity between these receptor-enriched regions and other regions in the brain, and found that the effects varied depending on the age of the participants.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Lisa Haase, Antonia Vehlen, Julia Strojny, Gregor Domes
Summary: This study found no significant changes in the cortisol awakening response (CAR) over the menstrual cycle, and no significant association with variations in estradiol and progesterone. These results suggest that CAR is largely robust against hormonal variations across the menstrual cycle.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Derek Schaeuble, Tyler Wallace, Sebastian A. Pace, Shane T. Hentges, Brent Myers
Summary: Depression and cardiovascular disease are influenced by daily life stress, but the biological mechanisms behind this connection are not well understood. This study shows that the ventromedial prefrontal cortex (vmPFC) plays a role in regulating stress responses and behavior, with sex-specific effects. In males, the vmPFC-PH circuitry promotes positive motivation and reduces stress responses, while in females it elevates stress responses. This suggests that cortical regulation of stress reactivity and behavior is mediated by projections to the hypothalamus in a sex-specific manner.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Jose M. Guzman, Montana H. Boone, Gabriela L. Suarez, Colter Mitchell, Christopher S. Monk, Luke W. Hyde, Nestor L. Lopez-Duran
Summary: The COVID-19 pandemic has led to increased life stress and internalizing disorders, with a disproportionate impact on women. This study focused on the neuroendocrinology of stress-related disorders and found that women have lower cortisol responses and higher DHEA responses to stress. However, lower cortisol and higher DHEA are associated with internalizing disorders in women, while the opposite is true in men. The study also examined the relationship between COVID-related stress and internalizing symptoms and found gender differences in the association between DHEA and cortisol and internalizing outcomes. These findings suggest distinct neuroendocrine pathways for stress-related disorders in young men and women.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Meriah L. Dejoseph, Keira B. Leneman, Alyssa R. Palmer, Emily R. Padrutt, Otiti A. Mayo, Daniel Berry
Summary: Childhood and adolescence are critical periods for the development of the stress response system. This study found a modest positive relation between the adrenocortical and sympathetic systems, as well as between the adrenocortical and parasympathetic systems. The strength of these associations varied based on methodological and sociodemographic characteristics.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Qiong Xiang, Jia-Sheng Tao, Shuai Dong, Xiao-Lin Liu, Liang Yang, Li-Ni Liu, Jing Deng, Xian-Hui Li
Summary: Chronic hyperglycemia accelerates the pathological process of cognitive dysfunction, but the heterogeneity of hippocampal cells under long-term high glucose conditions is not well known. In this study, single-cell RNA sequencing was performed on diabetic mice, and distinct cell sub-clusters and important genes involved in neuroplasticity regulation were identified.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Roger Mcintosh, Hannah Hoogerwoerd, Salman S. Ahmad, Cassandra Michel, Kaitlyn Dillon, Mahendra Kumar, Gail Ironson
Summary: The study found that a 4-session guided written emotional disclosure intervention led to significant reductions in total output and concentration of epinephrine in urine for up to 6 months in individuals living with HIV. This effect was especially pronounced in women. However, there were no significant changes in norepinephrine output in urine.
PSYCHONEUROENDOCRINOLOGY
(2024)
Article
Endocrinology & Metabolism
Meredith Gruhn, Adam Bryant Miller, Tory A. Eisenlohr-Moul, Sophia Martin, Matthew G. Clayton, Matteo Giletta, Paul D. Hastings, Matthew K. Nock, Karen D. Rudolph, George M. Slavich, Mitchell J. Prinstein, Margaret A. Sheridan
Summary: This study investigates how early life adversity characterized by threat impacts the association between neural activity and cortisol production during emotion processing. The results suggest that threat exposure may moderate the relationship between neural activation and cortisol response.
PSYCHONEUROENDOCRINOLOGY
(2024)