Contact person: Vibe G. Frøkjær

At NRU we use brain imaging methods to work with aspects of human brain biology that are critical for risk mechanisms and manifest psychiatric disorders. We use a multimodal imaging approach, which combines both structural and functional imaging and hold a special expertise in molecular imaging of key features of the serotonin signaling system. A system which is profoundly involved in mood disorders, schizophrenia, neurodegenerative disorders and their treatment.

In particular, we are interested in serotonin brain biology as a driver of healthy adaptation to e.g. seasons, stressors, genetic make-up, personality, changes in sex-steroid hormone milieu and healthy navigation in social relations. With intervention models we work with the dynamic interplay between serotonin brain biology and steroid hormone systems as a driver of risk and resilience in mental health. Specifically we have conceptualized a risk model in order to map how sex-steroid hormone fluctuations may trigger depressive episodes as frequently seen in the transition from pregnancy to postpartum and to the menopausal state in women. Here we have provided direct evidence for sex-hormone manipulation to provoke subclinical depressive symptoms in about 12% of healthy volunteers, a phenomenon which was coupled to increases in serotonin transporter binding (which lowers synaptic serotonin), and correlated with the magnitude of sex-steroid (estradiol) decline. This strongly implies transiently compromised serotonin signalling in the mechanisms by which sex steroid hormone fluctuations provoke depressive symptoms in sensitive individuals. In the same cohort, we have further shown that sex-hormone manipulation (a) affects processing of emotional faces in a manner dependent on depressive responses to intervention and, intriguingly, (b) reduces brain responses to reward reflecting a reduced engagement in positive experiences. If translating to disturbed serotonin signalling and social motivation in a cohort of depressed mothers this will be seminal in understanding mechanisms that mobilize natural maternal care capacities and promote social bonding of paramount importance to mother and infant health.

We use both an experimental modelling approach and study naturally existing human models of risk or at-risk populations and patients. Our translational model work is often informed by hypothesis generating cross-sectional work anchored in our large and unique Cimbi database and biobank resource.

The endeavor of our work is to map brain architecture in risk and resilience to mental disorders to provide a rationale for targeted prevention and treatment. Ideally, our work will also support a stratified approach to diagnosing and treating neuropsychiatric disorders across existing diagnostic entities including major depressive episodes, which is one of our largest public health problems at present.

We collaborate closely with Professor Anja Pinborg from the Department of Obstetrics/Gynaecology at Hvidovre Hospital and Mental Health Services Copenhagen, and with Department of Psychology, University of Copenhagen. Also we are involved in ongoing collaborations with international partners at University of British Columbia, Canada, John Hopkins University, US, Uppsala University, Sweden, and Max-Planck Institute of Psychiatry, Germany.

Examples of recent publications:

  • Rasmussen H, Frokjaer VG, Hilker RW, Madsen J, Anhøj S, Oranje B, Pinborg LH, Glenthøj B, Knudsen GM. Low frontal serotonin 2A receptor binding is a state marker for schizophrenia?  Eur Neuropsychopharmacol. 2016 Jul;26(7):1248-50
  • Miskowiak KW, Vinberg M, Glerup L, Paulson OB, Knudsen GM, Ehrenreich H, Harmer CJ, Kessing LV, Siebner HR, Macoveanu J. Neural correlates of improved executive function following erythropoietin treatment in mood disorders. Psychol Med. 2016 Jun;46(8):1679-91
  • Mc Mahon B, Andersen SB, Madsen MK, Hjordt LV, Hageman I, Dam H, Svarer C, da Cunha-Bang S, Baaré W, Madsen J, Hasholt L, Holst K, Frokjaer VG, Knudsen GM. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder. Brain. 2016 May;139(Pt 5):1605-14
  • Jakobsen GR, Fisher PM, Dyssegaard A, McMahon B, Holst KK, Lehel S, Svarer C, Jensen PS, Knudsen GM, Frokjaer VG. Brain serotonin 4 receptor binding is associated with the cortisol awakening response. Psychoneuroendocrinology. 2016 May;67:124-32
  • Stenbæk DS, Fisher PM, Budtz-Jørgensen E, Pinborg A, Hjordt LV, Jensen PS, Knudsen GM, Frokjaer VG. Sex hormone manipulation slows reaction time and increases labile mood in healthy women. Psychoneuroendocrinology. 2016 Feb 26;68:39-46
  • Henningsson S, Madsen KS, Pinborg A, Heede M, Knudsen GM, Siebner HR, Frokjaer VG. Role of emotional processing in depressive responses to sex-hormone manipulation; a pharmacological fMRI study. Translational Psychiatry 2015 Dec 1;5:e688. doi: 10.1038/tp.2015.184
  • Frokjaer VG, Pinborg A, Holst KK, Overgaard A, Henningsson S, Heede M, Larsen EC, Jensen PS, Agn M, Nielsen AP, Stenbæk DS, da Cunha-Bang S, Lehel S, Siebner HR, Mikkelsen JD, Svarer C, Knudsen GM. Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study. Biol Psychiatry. 2015 Oct 15;78(8):534-43