Skip to main content Accessibility help

Brain activation during emotion regulation in women with premenstrual dysphoric disorder

  • Nicole Petersen (a1), Dara G. Ghahremani (a1), Andrea J. Rapkin (a2), Steven M. Berman (a1), Letty Liang (a1) and Edythe D. London (a1) (a3) (a4)...



Difficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.


On the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.


Women with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.


During the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.


Corresponding author

Address for correspondence: Andrea J. Rapkin, E-mail:


Hide All

Both authors contributed equally to this work



Hide All
Andersson, J, Jenkinson, M and Smith, S (2007) Non-linear registration, aka Spatial normalisation. FMRIB Technical Report.
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Washington, DC: Author.
Baller, EB, Wei, SM, Kohn, PD, Rubinow, DR, Alarcon, G, Schmidt, PJ and Berman, KF (2013) Abnormalities of dorsolateral prefrontal function in women with premenstrual dysphoric disorder: a multimodal neuroimaging study. American Journal of Psychiatry 170, 305314.
Banks, SJ, Eddy, KT, Angstadt, M, Nathan, PJ and Phan, KL (2007) Amygdala-frontal connectivity during emotion regulation. Social Cognitive Affective Neuroscience 2, 303312.
Bannbers, E, Gingnell, M, Engman, J, Morell, A, Comasco, E, Kask, K, Garavan, H, Wikstrom, J and Sundstrom Poromaa, I (2012) The effect of premenstrual dysphoric disorder and menstrual cycle phase on brain activity during response inhibition. Journal of Affective Disorders 142, 347350.
Berman, KF, Schmidt, PJ, Rubinow, DR, Danaceau, MA, Van Horn, JD, Esposito, G, Ostrem, JL and Weinberger, DR (1997) Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Proceedings of the National Academy of Sciences USA 94, 88368841.
Birtch, RL, Olatunbosun, OA and Pierson, RA (2006) Ovarian follicular dynamics during conventional vs. continuous oral contraceptive use. Contraception 73, 235243.
Bloch, M, Schmidt, PJ and Rubinow, DR (1997) Premenstrual syndrome: evidence for symptom stability across cycles. American Journal of Psychiatry 154, 17411746.
Buhle, JT, Silvers, JA, Wager, TD, Lopez, R, Onyemekwu, C, Kober, H, Weber, J and Ochsner, KN (2014) Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies. Cerebral Cortex 24, 29812990.
Cunningham-Bussel, AC, Root, JC, Butler, T, Tuescher, O, Pan, H, Epstein, J, Weisholtz, DS, Pavony, M, Silverman, ME, Goldstein, MS, Altemus, M, Cloitre, M, Ledoux, J, Mcewen, B, Stern, E and Silbersweig, D (2009) Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli. Psychoneuroendocrinology 34, 694704.
Davis, AR, Kroll, R, Soltes, B, Zhang, N, Grubb, GS and Constantine, GD (2008) Occurrence of menses or pregnancy after cessation of a continuous oral contraceptive. Fertility and Sterility 89, 10591063.
Dickerson, LM, Mazyck, PJ and Hunter, MH (2003) Premenstrual syndrome. American Family Physician 67, 17431752.
Domes, G, Schulze, L, Bottger, M, Grossmann, A, Hauenstein, K, Wirtz, PH, Heinrichs, M and Herpertz, SC (2010) The neural correlates of sex differences in emotional reactivity and emotion regulation. Human Brain Mapping 31, 758769.
Duijkers, I, Engels, L and Klipping, C (2005) Length of the menstrual cycle after discontinuation of oral contraceptives. Gynecological Endocrinology 20, 7479.
Endicott, J, Nee, J and Harrison, W (2006) Daily record of severity of problems (DRSP): reliability and validity. Archives of Womens Mental Health 9, 4149.
Epperson, CN, Steiner, M, Hartlage, SA, Eriksson, E, Schmidt, PJ, Jones, I and Yonkers, KA (2012) Premenstrual dysphoric disorder: evidence for a new category for DSM-5. American Journal of Psychiatry 169, 465475.
Erk, S, Mikschl, A, Stier, S, Ciaramidaro, A, Gapp, V, Weber, B and Walter, H (2010) Acute and sustained effects of cognitive emotion regulation in major depression. Journal of Neuroscience 30, 1572615734.
First, MB, Spitzer, RL, Gibbon, M and Williams, JBW (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. New York State: Psychiatric Institute.
Gingnell, M, Bannbers, E, Wikstrom, J, Fredrikson, M and Sundstrom-Poromaa, I (2013) Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli. European Journal of Neuropsychopharmacology 23, 14741483.
Gingnell, M, Morell, A, Bannbers, E, Wikstrom, J and Sundstrom Poromaa, I (2012) Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder. Hormones and Behavior 62, 400406.
Goldin, PR, Mcrae, K, Ramel, W and Gross, JJ (2008) The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biological Psychiatry 63, 577586.
Greicius, MD, Krasnow, B, Reiss, AL and Menon, V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences USA 100, 253258.
Halbreich, U, Borenstein, J, Pearlstein, T and Kahn, LS (2003) The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology 28( suppl. 3), 123.
Hantsoo, L and Epperson, CN (2015) Premenstrual dysphoric disorder: epidemiology and treatment. Current Psychiatry Reports 17, 87.
Hong, JP, Park, S, Wang, HR, Chang, SM, Sohn, JH, Jeon, HJ, Lee, HW, Cho, SJ, Kim, BS, Bae, JN and Cho, MJ (2012) Prevalence, correlates, comorbidities, and suicidal tendencies of premenstrual dysphoric disorder in a nationwide sample of Korean women. Social Psychiatry and Psychiatric Epidemiology 47, 19371945.
Jenkinson, M and Smith, S (2001) A global optimisation method for robust affine registration of brain images. Medical Image Analysis 5, 143156.
Johnstone, T, Van Reekum, CM, Urry, HL, Kalin, NH and Davidson, RJ (2007) Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience 27, 88778884.
Koenigsberg, HW, Fan, J, Ochsner, KN, Liu, X, Guise, K, Pizzarello, S, Dorantes, C, Tecuta, L, Guerreri, S, Goodman, M, New, A, Flory, J and Siever, LJ (2010) Neural correlates of using distancing to regulate emotional responses to social situations. Neuropsychologia 48, 18131822.
Koenigsberg, HW, Fan, J, Ochsner, KN, Liu, X, Guise, KG, Pizzarello, S, Dorantes, C, Guerreri, S, Tecuta, L, Goodman, M, New, A and Siever, LJ (2009) Neural correlates of the use of psychological distancing to regulate responses to negative social cues: a study of patients with borderline personality disorder. Biological Psychiatry 66, 854863.
Kohn, N, Eickhoff, SB, Scheller, M, Laird, AR, Fox, PT and Habel, U (2014) Neural network of cognitive emotion regulation – an ALE meta-analysis and MACM analysis. NeuroImage 87, 345355.
Lang, PJ, Bradley, MM and Cuthbert, BN (2008) International affective picture system (IAPS): affective ratings of pictures and instruction manual. Technical Report.
Lopez, LM, Kaptein, AA and Helmerhorst, FM (2012) Oral contraceptives containing drospirenone for premenstrual syndrome. The Cochrane Database of Systematic Reviews 2, CD006586.
Mcrae, K, Misra, S, Prasad, AK, Pereira, SC and Gross, JJ (2012) Bottom-up and top-down emotion generation: implications for emotion regulation. Social Cognitive and Affective Neuroscience 7, 253262.
Ochsner, KN and Gross, JJ (2005) The cognitive control of emotion. Trends in Cognitive Sciences 9, 242249.
Ochsner, KN, Ray, RD, Cooper, JC, Robertson, ER, Chopra, S, Gabrieli, JD and Gross, JJ (2004) For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. NeuroImage 23, 483499.
Ochsner, KN, Silvers, JA and Buhle, JT (2012) Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion. Annals of the New York Academy of Sciences 1251, E124.
Oldfield, RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97113.
Petersen, N and Cahill, L (2015) Amygdala reactivity to negative stimuli is influenced by oral contraceptive use. Social Cognitive and Affective Neuroscience 10, 12661272.
Petersen, N, London, ED, Liang, L, Ghahremani, DG, Gerards, R, Goldman, L and Rapkin, AJ (2016) Emotion regulation in women with premenstrual dysphoric disorder. Archives of Women's Mental Health 19, 891898.
Pilver, CE, Libby, DJ and Hoff, RA (2013) Premenstrual dysphoric disorder as a correlate of suicidal ideation, plans, and attempts among a nationally representative sample. Social Psychiatry and Psychiatric Epidemiology 48, 437446.
Rapkin, AJ, Berman, SM, Mandelkern, MA, Silverman, DH, Morgan, M and London, ED (2011) Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biological Psychiatry 69, 374380.
Rapkin, AJ and Winer, SA (2009) Premenstrual syndrome and premenstrual dysphoric disorder: quality of life and burden of illness. Expert Rev Pharmacoeconomics & Outcomes Research 9, 157170.
Reuveni, I, Dan, R, Segman, R, Evron, R, Laufer, S, Goelman, G, Bonne, O and Canetti, L (2016) Emotional regulation difficulties and premenstrual symptoms among Israeli students. Archives of Women's Mental Health 19, 10631070.
Ritchey, M, Dolcos, F, Eddington, KM, Strauman, TJ and Cabeza, R (2011) Neural correlates of emotional processing in depression: changes with cognitive behavioral therapy and predictors of treatment response. Journal of Psychiatric Research 45, 577587.
Silvers, JA, Insel, C, Powers, A, Franz, P, Helion, C, Martin, RE, Weber, J, Mischel, W, Casey, BJ and Ochsner, KN (2016) vlPFC-vmPFC-amygdala interactions underlie age-related differences in cognitive regulation of emotion. Cerebral Cortex 27, 35023514.
Silvers, JA, Shu, J, Hubbard, AD, Weber, J and Ochsner, KN (2015) Concurrent and lasting effects of emotion regulation on amygdala response in adolescence and young adulthood. Developmental Science 18, 771784.
Wager, TD, Davidson, ML, Hughes, BL, Lindquist, MA and Ochsner, KN (2008) Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron 59, 10371050.
Wittchen, HU, Becker, E, Lieb, R and Krause, P (2002) Prevalence, incidence and stability of premenstrual dysphoric disorder in the community. Psychological Medicine 32, 119132.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Petersen et al supplementary material
Petersen et al supplementary material 1

 Word (170 KB)
170 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed