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Rigshospitalet

Neuropsychiatry

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 and synaptic density. Systems which are profoundly involved in mood disorders, schizophrenia, neurodegenerative disorders and their treatments.

In particular, we are interested in serotonin brain biology as a driver of (mal)adaptation to e.g. seasons, stressors, genetic make-up, personality, changes in sex-steroid hormone milieu and its role in healthy navigation in social relations. We work with experimental medicine study designs (e.g. placebo-controlled intervention models) as well as natural existing human models in high-risk or patient cohorts. Our translational model work is often informed by hypothesis generating cross-sectional work anchored in our large and unique Cimbi database and biobank resource and/or National Health Registers. We also leverage our deep phenotyping resources with relevant read outs of longer-term outcomes from National Health Registers, e.g. as part of BrainDrugs.

Specifically, we run several projects 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 and has repeatedly high-lighted estrogen withdrawal related risk mechanisms. We also work with clinical translations and evaluate candidate preventive strategies for disruptions of early risk mechanisms in women at high-risk for perinatal depression design (i.e. short-term estrogen vs placebo patch, The MAMA trial), with read-outs on both maternal and infant mental health and early neurocognitive development.

The endeavor of our work is to map brain architecture in risk and resilience to brain disorders with psychological manifestations 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 Martin Balslev-Jørgensen and Professor Kamilla Miskowiak, Mental Health Services Copenhagen and Dept of Psychology University of Copenhagen, Porfessor Øjvind Lidegaard and Professor Anja Pinborg from Department of Obstetrics/Gynaecology at Rigshospitalet, and Trine Munk-Olsen, The National Centre for Register-based Research, Århus, Denmark. Also, we collaborate with international partners at CAMH, Canada, Yale US, Uppsala University, Sweden, and Max-Planck Institute of Psychiatry, München, Germany and Salzburg university, Austria.

Examples of recent publications:

  • Larsen SV, Mikkelsen AP, Ozenne B, Lidegaard Ø, Munk-Olsen T, Frokjaer VG. Association between intrauterine system hormone dose and depression risk. Am J Psychiatry. doi: 10.1176/appi.ajp.20230909) In press
  • Høgh S, Lange EØ, Høgsted ES, Larsen K, Hegaard HK, Borgsted C, Frokjaer VG. The cortisol awakening response is blunted in healthy women early postpartum. Psychoneuroendocrinology. 2024 Apr 13;165:107048. doi: 10.1016/j.psyneuen.2024.107048. Epub ahead of print
  • Fu CHY, Antoniades M, Erus G, Garcia JA, Fan Y, Arnone D, Arnott SR, Chen T, Choi KS, Fatt CC, Frey BN, Frokjaer VG, et al. Neuroanatomical dimensions in medication- free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo. Nature Mental Health. Accepted November 17th 2023
  • Noachtar IA, Frokjaer VG, Pletzer B. Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal. JAMA Netw Open. 2023 Sep 5;6(9):e2335957
  • Rasmussen AL, Larsen SV, Ozenne B, Köhler-Forsberg K, Stenbæk DS, Jørgensen MB, Giraldi A, Frokjaer VG. Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression-a NeuroPharm study. Transl Psychiatry. 2023 Jul 6;13(1):247
  • Larsen SV, Mikkelsen AP, Lidegaard Ø, Frokjaer VG. Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression. JAMA Psychiatry. 2023 Jul 1;80(7):682-689
  • Sankar A, Ozenne B, Dam VH, Svarer C, Jørgensen MB, Miskowiak KW, Frokjaer VG, Knudsen GM, Fisher PM. Association between brain serotonin 4 receptor binding and reactivity to emotional faces in depressed and healthy individuals. Transl Psychiatry. 2023 May 11;13(1):165
  • Köhler-Forsberg K, Dam VH, Ozenne B, Sankar A, Beliveau V, Landman EB, Larsen SV, Poulsen AS, Ip CT, Jørgensen A, Meyer M, Stenbæk DS, Eiberg HRL, Madsen J, Svarer C, Jørgensen MB, Frokjaer VG, Knudsen GM. Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction. JAMA Psychiatry. 2023 Apr 1;80(4):296-304
  • Jensen KHR, Dam VH, Ganz M, Fisher PM, Ip CT, Sankar A, Marstrand-Joergensen MR, Ozenne B, Osler M, Penninx BWJH, Pinborg LH, Frokjaer VG, Knudsen GM, Jørgensen MB. Deep phenotyping towards precision psychiatry of first-episode depression - the Brain Drugs-Depression cohort. BMC Psychiatry. 2023 Mar 9;23(1):151
  • Sankar A, Ziersen SC, Ozenne B, Beaman EE, Dam VH, Fisher PM, Knudsen GM, Kessing LV, Frokjaer V, Miskowiak KW. Association of neurocognitive function with psychiatric hospitalization and socio-demographic conditions in individuals with bipolar and major depressive disorders. EClinicalMedicine. 2023 Mar 24;58:101927
  • Fu CHY, Erus G, Fan Y, Antoniades M, Arnone D, Arnott SR, Chen T, Choi KS, Fatt CC, Frey BN, Frokjaer VG, Ganz M, Garcia J, Godlewska BR, Hassel S, Ho K, McIntosh AM, Qin K, Rotzinger S, Sacchet MD, Savitz J, Shou H, Singh A, Stolicyn A, Strigo I, Strother SC, Tosun D, Victor TA, Wei D, Wise T, Woodham RD, Zahn R, Anderson IM, Deakin JFW, Dunlop BW, Elliott R, Gong Q, Gotlib IH, Harmer CJ, Kennedy SH, Knudsen GM, Mayberg HS, Paulus MP, Qiu J, Trivedi MH, Whalley HC, Yan CG, Young AH, Davatzikos C. AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder: COORDINATE-MDD consortium design and rationale. BMC Psychiatry. 2023 Jan 23;23(1):59.