Liisa Hantsoo, Ph.D.

Premenstrual dysphoric disorder (PMDD) is a mood disorder affecting millions of women worldwide. Per year, it affects more women than postpartum depression. Symptoms include irritability, low mood, or anxiety, that are limited to the week or so prior to menses. The neurobiology of this disorder is grossly understudied. My work aims to examine the role of suboptimal central nervous system (CNS) sensitivity to neuroactive steroids (such as progesterone and its metabolites) in PMDD. Specifically, I am examining how neuroactive steroids fluctuate across the menstrual cycle and modulate stress response in women who have PMDD, and how this might be affected by treatment with antidepressant medications. You can learn more about my active PMDD research studies here and here.

My research in PMDD has been funded by NIMH K23 , R21, and R01 awards, and a NARSAD Young Investigator Award. I have published on PMDD in journals including Lancet Psychiatry and the American Journal of Psychiatry. I have also collaborated with companies such as Clue and Flo on research concerning women’s health.

RELEVANT PUBLICATIONS:

Cunningham AC, Prentice C, Peven K, Wickham A, Bamford R, Radovic T, Klepchukova A, Fomina M, Cunningham K, Hill S, Hantsoo L, Payne J, Zhaunova L, Ponzo S. (2024). Efficacy of the Flo App in Improving Health Literacy, Menstrual and General Health, and Well-Being in Women: Pilot Randomized Controlled Trial.JMIR Mhealth Uhealth, 12:e54124.

Miller KN, Standeven L, Morrow AL, Payne JL, Epperson CN, Hantsoo L. (2024). GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder.Psychoneuroendocrinology,160:106684.

Barone JC, Ho A, Osborne LM, Eisenlohr-Moul TA, Morrow AL, Payne JL, Epperson CN, Hantsoo L. (2024). Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation. Psychoneuroendocrinology, 169:107145.

Hannan K, Li X, Mehta A, Yenokyan G, Payne JL, Shea AA, Hantsoo L. (2024). Mood symptoms and gut function across the menstrual cycle in individuals with premenstrual syndrome. Horm Behav., 166:105634.

Standeven LR, Bajaj M, McEvoy K, Shirinian D, Voegtline K, Osborne LM, Payne JL, Hantsoo L. (2024). The link between childhood traumatic events and the continuum of premenstrual disorders. Front Psychiatry, 15:1443352.

Hantsoo L, Payne JL. (2024). Premenstrual Dysphoric Disorder Affects Five Times as Many Individuals as Postpartum Depression, But Receives 80% Less NIH Research Funding. J Womens Health, 33(10): 1296-1297.

Gordon JL, Chenji S, Di Florio A, Hantsoo L, MacDonald S, Peters JR, Ross JM, Schmalenberger K, Eisenlohr-Moul TA. (2024). Suicidality should be considered for inclusion in the diagnostic criteria for PMDD. Lancet Psychiatry, S2215-0366(24)00288-8.

Hantsoo L, Payne JL. (2023). Towards understanding the biology of premenstrual dysphoric disorder: From genes to GABA. Neurosci Biobehav Rev, 149:105168.

Hantsoo, L., Rangaswamy S, Voegtline K, Salimgaraev R, Zhaunova L, Payne JL. (2022). Premenstrual symptoms across the lifespan in an international sample: data from a mobile application. Arch Womens Ment Health, 25(5):903-910. 

Hantsoo L, Sajid H, Murphy L, Buchert B, Barone JC, Raja S, Eisenlohr-Moul T. (2022). Patient Experiences of Health Care Providers in Premenstrual Dysphoric Disorder: Examining the Role of Provider Specialty. J Womens Health, 31(1):100-109.

Hantsoo L, Grillon C, Sammel M, Johnson R, Marks J, Epperson CN. (2021). Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder.Psychopharmacology,238(10):2985-2997.

Hantsoo, L., Riddle, J. (2021). Treatment of Premenstrual Dysphoric Disorder (PMDD): Advances and Challenges. Advances in Psychiatry and Behavioral Health, 1(1), 91-106.

Hantsoo L, Epperson CN. (2020). Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle. Neurobiol Stress, 12:100213.

Hantsoo L., Golden C.E.M., Kornfield S., Grillon C., Epperson C.N. (2018). Startling Differences: Using the Acoustic Startle Response to Study Sex Differences and Neurosteroids in Affective Disorders. Current Psychiatry Reports. 2018 May 18;20(6):40.

Hantsoo L., Epperson C.N. (2017). Anxiety Disorders Among Women: A Female Lifespan Approach. American Psychiatric Association Focus:  The Journal of Lifelong Learning in Psychiatry, 15(2), 162-172.

Epperson, C.N., Hantsoo, L. (2016). Making Strides to Simplify Diagnosis of Premenstrual Dysphoric Mood Disorder. American Journal of Psychiatry, 174(1): 6–7.

Hantsoo L., Epperson C.N. (2015). Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Current Psychiatry Reports, 17(11):87.

Epperson, C.N., Kim, D.R., Hantsoo, L. (2015). Premenstrual Dysphoric Mood Disorder. In Stolerman, I.P. and Price, L.H. (Eds.) Encyclopedia of Psychopharmacology. (2nd ed., pp 1348-1351). New York: Springer.

Epperson, C.N., Hantsoo, L. Menstruation and PMDD.  (2014). In D. Barnes (Ed.) Women’s Reproductive Mental Health Across the Lifespan (pp 49-72). New York: Springer.

Photo by Verne Ho on Unsplash.

Work by my Ph.D. mentor, Dr. Janice Kiecolt-Glaser, shows that individuals who experienced significant stress as children have altered immune function and response to stress as adults. Recently, there has been interest in transgenerational effects of stress — how stress affects not only an individual, but her offspring. This is particularly relevant in pregnancy. My work in this area has examined physiologic response to acute stress, particularly immune response, among pregnant women who had or had not experienced significant adversity in childhood.

I also worked on Dr. Neill Epperson’s P50 project examining how prepubertal adversity in women may reprogram the brain toward stress dysregulation, and whether this interacts with phases of dynamic hormonal flux across the female life span, particularly pregnancy. You can read more about the “Prepubertal Stress, Windows of Risk & Sex Bias for Affective Disturbance” study here.

RELEVANT PUBLICATIONS:

Duffy, K. A., Sammel, M. D., Johnson, R. L., Kim, D. R., Wang, E. Y., Ewing, G., Hantsoo, L., Kornfield, S. L., Bale, T. L., & Epperson, C. N. (2023). Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner. Biology of Sex Differences, 14(1), 7. 

Hantsoo L, Duffy KA, Sammel M, Johnson RL, Kim D, Grillon C, Epperson CN. (2023). Enduring impact of childhood adversity: Affective modulation of acoustic startle response during pregnancy and postpartum. Physiol Behav, 258:114031.

Hantsoo L, Jašarević E, Criniti S, McGeehan B, Tanes C, Sammel MD, Elovitz MA, Compher C, Wu G, Epperson CN. (2019) Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy. Brain Behav Immun., 75:240-250.

Hantsoo L, Kornfield S, Anguera MC, Epperson CN. Inflammation: A Proposed Intermediary Between Maternal Stress and Offspring Neuropsychiatric Risk. Biol Psychiatry, S0006-3223(18)31795-5. doi: 10.1016/j.biopsych.2018.08.018

Morrison, K.E., Epperson, C.N., Sammel, M.D., Ewing, G., Podcasy, J.S., Hantsoo, L., Kim, D.R., Bale T.L. (2017). Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice. Biological Psychiatry, 81(8):693-701.

RELEVANT PRESENTATIONS:

Hantsoo, L., Sammel, M.D., Ewing, G.E., Morrison, K., Elovitz, M., Bale, T., Epperson, C.N. Maternal Adverse Childhood Experiences: Impact on Perinatal Glucocorticoid-Inflammatory Stress Response and Offspring Hypothalamic Pituitary Adrenal (HPA) Axis Development. American College of Neuropsychopharmacology (ACNP) Annual Meeting, December 2017.

Hantsoo, L. Sex Differences in Structure and Function of Hypothalamic Pituitary Adrenal Axis (HPA-A) in Offspring of Women with Adverse Childhood Experiences.” Symposium Presentation at American Conference on Perinatal Mental Health, Chicago, IL. November 2017.

Hantsoo, L., Elovitz, M., Podcasy J.S., Epperson, C.N. (2017). Maternal Early Life Stress is Associated with Increased Interleukin-6 (IL-6) Response to Acute Stress During Pregnancy. Association for Psychological Science (APS) 29th Annual Convention. May 25-28, 2017. Boston, MA.

Hantsoo, L., Podcasy J.S., Elovitz, M., Epperson, C.N. (2017). Early Life Stress (ELS) is Associated with Heightened Inflammatory Response to Acute Stress Among Pregnant Women. Annual Scientific Meeting of the Society of Biological Psychiatry (SOBP). May 18-20, 2017. San Diego, CA.

Hantsoo, L., Sammel, M.D., Wang, E., Ewing, G., Epperson, C.N. (2017). Maternal early life stress (ELS) impact on offspring hypothalamic pituitary adrenal (HPA) axis:  Differential effects in male versus female fetal adrenal volume. Organization for the Study of Sex Differences (OSSD) Annual Meeting. May 15-18, 2017. Montreal, Quebec, Canada.

Hantsoo, L. Impact of Maternal Childhood Adversity on Maternal Stress Reactivity and Infant Outcomes. Symposium Presentation at Anxiety and Depression (ADAA) Annual Conference, Philadelphia, PA, March 2016.

Photo by Piepie on Pixabay

The human gut is populated by a diverse array of microbiota. These microorganisms play important roles, including regulating immune function. Recent work by our collaborators, using a mouse model, found that stress altered the gut microbiota of female mice during pregnancy, and that these alterations were also reflected in the offspring gut communities. My current research is examining the question of maternal stress and gut microbiome composition in humans.

My research on the gut microbiome has been funded by an NIH R03 award, a Johns Hopkins Specialized Centers of Research Excellence (SCORE) on Sex Differences Seed Grant, and a March of Dimes Early Career Investigator Award.

RELEVANT PUBLICATIONS:

Hannan K, Li X, Mehta A, Yenokyan G, Payne JL, Shea AA, Hantsoo L. (2024). Mood symptoms and gut function across the menstrual cycle in individuals with premenstrual syndrome. Horm Behav, 166:105634.

Hantsoo L, Zemel BS. Stress gets into the belly: Early life stress and the gut microbiome. (2021). Behav Brain Res., 24;414:113474.

Hantsoo L, Jašarević E, Criniti S, McGeehan B, Tanes C, Sammel MD, Elovitz MA, Compher C, Wu G, Epperson CN. (2019) Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy. Brain Behav Immun. 2019 Jan;75:240-250.

RELEVANT PRESENTATIONS:

Hantsoo, L. “Depressive Symptoms, Obesity, Adverse Childhood Experiences and the Gut Microbiome: Connections with Inflammation in Pregnancy.” (2024). International Marcé Society Biennial Conference, Barcelona, Spain.

Hantsoo, L. “Adverse Childhood Experiences, the Gut Microbiome and Inflammation in Pregnancy.” (2019). 8th World Congress of the International Association for Women’s Mental Health (IAWMH), Paris, France

Hantsoo, L., Criniti, S., McGeehan, B., Tanes, C., Elovitz, M., Compher, C., Wu, G., Epperson, C.N. (2018). Adverse Childhood Experiences are Associated with Altered Human Adult Gut Microbiome.  Annual Scientific Meeting of the Society of Biological Psychiatry (SOBP). New York, NY.

Photo by Liisa Hantsoo. This is a sculpture called “Oozing” by Eva Fabregas, exhibited at MACBA: Museu d'Art Contemporani de Barcelona.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age. Women with PCOS have hormonal irregularities accompanied by dysregulated menstrual cycle function, and are at risk for depression. I had the opportunity to work on a collaboration with Dr. Anuja Dokras, a PCOS expert, as her team at the University of Pennsylvania looked at mental health and stress response among women with PCOS. More recently, I have collaborated on research examining neuroactive steroids and mood symptoms in PCOS.

RELEVANT PUBLICATIONS:

Standeven, LR, Ho, A., Hantsoo, L. (2024). Bridging the Gap: Integrating Awareness of Polycystic Ovary Syndrome into Mental Health Practice. American Psychiatric Association Focus:  The Journal of Lifelong Learning in Psychiatry, 22(101), 53-62. 

Standeven, L., Hannan, K., Singh, B., Hantsoo, L. (2023). Polycystic Ovary Syndrome: A Guide for Psychiatric Providers. Advances in Psychiatry and Behavioral Health, 3(1), 91-101.

Standeven LR, Olson E, Leistikow N, Payne JL, Osborne LM, Hantsoo L. (2021). Polycystic Ovary Syndrome, Affective Symptoms, and Neuroactive Steroids: a Focus on Allopregnanolone. Curr Psychiatry Rep, 23(6):36.

Cooney, L.G., Milman, L.W., Hantsoo, L., Kornfield S, Sammel MD, Allison KC, Epperson CN, Dokras A. (2018). Cognitive behavioral therapy improves weight loss and quality of life in women with polycystic ovary syndrome: a randomized clinical trial.Fertil Steril. 2018 Jun 13. pii: S0015-0282(18)30283-8. doi: 10.1016/j.fertnstert.2018.03.028. [Epub ahead of print]

RELEVANT PRESENTATIONS:

Co-Chair, Symposium: “From the Pill to PCOS: Gonadal Steroids And Mood Symptoms Across The Reproductive Lifespan.”  North American Society for Psychosocial Obstetrics and Gynecology (NASPOG) Biennial Meeting, Philadelphia, PA.

Image by Roger A. Gorski, PhD, Professor of Neurobiology, Director Laboratory of Neuroendocrinology, Brain Research Institute, UCLA, via Health Education Assets Library (HEAL).

Integrating mobile health (mHealth) — the use of mobile phones and wireless technology — in mental healthcare is an interest of mine. Much of my work in the mHealth realm has focused on use of mobile or computer-assisted technology to assist pregnant women with mental health concerns and limited access to care, and more recently on the use of mobile technologies relative to the menstrual cycle.

RELEVANT PUBLICATIONS:

Cunningham AC, Prentice C, Peven K, Wickham A, Bamford R, Radovic T, Klepchukova A, Fomina M, Cunningham K, Hill S, Hantsoo L, Payne J, Zhaunova L, Ponzo S. (2024). Efficacy of the Flo App in Improving Health Literacy, Menstrual and General Health, and Well-Being in Women: Pilot Randomized Controlled Trial. JMIR Mhealth Uhealth, 12:e54124.

Hantsoo L, Rangaswamy S, Voegtline K, Salimgaraev R, Zhaunova L, Payne JL. (2022). Premenstrual symptoms across the lifespan in an international sample: data from a mobile application. Arch Womens Ment Health, 25(5):903-910.

Hantsoo, L., Criniti, S., Khan, A., Epperson, Moseley, M., Kincler, N., Faherty, L.J., Epperson, C.N., Bennett, I.M. (2018). A mobile application for monitoring and management of depressed mood in a vulnerable pregnant population. Psychiatr Serv., 69(1):104-107.

Hantsoo, L., Podcasy, J.S., Sammel, M.D., Epperson, C.N., Kim, D.R. (2017). Pregnancy and the Acceptability of Computer-Based versus Traditional Mental Health Treatments. Journal of Women’s Health, 2017 Oct;26(10):1106-1113.

Faherty, L.J., Hantsoo, L., Appleby, D., Sammel, M.D., Bennett, I.M., Wiebe, D.J. (2017). Movement Patterns in Women at Risk for Perinatal Depression: Use of a Mood-Monitoring Mobile Application in Pregnancy. Journal of the American Medical Informatics Association. 2017 Jul 1;24(4):746-753.

Kim, D.R., Hantsoo, L., Thase, M., Sammel, M.D., Epperson, C.N. (2014). Computer-Assisted Cognitive Behavioral Therapy for Pregnant Women with Major Depressive Disorder. Journal of Womens Health (Larchmt), 23(10):842-8.

Hantsoo L, Epperson CN, Thase ME, Kim DR. (2013). Antepartum depression: treatment with computer-assisted cognitive-behavioral therapy. Am J Psychiatry, 170(8):929-30.

Bennett, I.M., Palmer, S.C., Nicholson, J., Hantsoo, L., Rinaldi, J., Coyne, J.  (2009). "One end has nothing to do with the other": Patient attitudes regarding help seeking intention for depression in gynecologic and obstetric settings. Archives of Women's Mental Health, 12, 301–308.

Photo by Lauren Mancke on Unsplash.

Hormones such as estradiol and testosterone can influence mood, behavior and physiology. This is particularly relevant when considering sex differences in psychiatric disorders. (For instance, women are roughly twice as likely to have depressive disorders as men.) NIH has called for closer consideration of sex as a biological variable in clinical research. In my work, I am interested in how sex and hormonal status influence response to stress, which is often a contributing factor to depression.

RELEVANT PUBLICATIONS

Duffy KA, Sammel MD, Johnson RL, Kim DR, Wang EY, Ewing G, Hantsoo L, Kornfield SL, Bale TL, Epperson CN. (2023). Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner.Biol Sex Differ, 14(1):7.

Hantsoo L, Kornfield S, Iannelli C, Podcasy J, Metzger D, Sammel MD, Epperson CN. (2019). Glucocorticoid-immune response to acute stress in women and men living with HIV. J Behav Med., 42(6):1153-1158.

Nguyen, H.B., Loughead, J., Lipner, E., Hantsoo, L., Kornfield, S., Epperson, C.N. (2019) What Has Sex Got To Do With It? The Role of Hormones in the Transgender Brain. Neuropsychopharmacology, 44(1):22-37

Nguyen HB, Chavez AM, Lipner E, Hantsoo L, Kornfield SL, Davies RD, Epperson CN. (2018). Gender-Affirming Hormone Use in Transgender Individuals: Impact on Behavioral Health and Cognition.Curr Psychiatry Rep, 20(12):110.

Hantsoo L, Golden CEM, Kornfield S, Grillon C, Epperson CN. (2018). Startling Differences: Using the Acoustic Startle Response to Study Sex Differences and Neurosteroids in Affective Disorders.Curr Psychiatry Rep, 20(6):40.

Kornfield SL, Hantsoo L, Epperson CN. (2018). What Does Sex Have to Do with It? The Role of Sex as a Biological Variable in the Development of Posttraumatic Stress Disorder.Curr Psychiatry Rep, 20(6):39.

Hantsoo L, Epperson CN. (2017). Anxiety Disorders Among Women: A Female Lifespan Approach. Focus (Am Psychiatr Publ), 15(2):162-172.

Hantsoo L, Czarkowski KA, Child J, Howes C, Epperson CN. (2014). Selective serotonin reuptake inhibitors and endothelial function in women. J Womens Health (Larchmt). 2014 Jul;23(7):613-8.

Hantsoo L, Khou CS, White CN, Ong JC. (2013). Gender and cognitive-emotional factors as predictors of pre-sleep arousal and trait hyperarousal in insomnia. J Psychosom Res. 2013 Apr;74(4):283-9.

Photo by Amy Shamblen on Unsplash.