Longitudinal hair cortisol in bipolar disorder and a mechanism based on HPA dynamics
Tomer Milo,
Lior Maimon,
Ben Cohen,
Dafna Haran,
Dror Segman,
Tamar Danon,
Anat Bren,
Avi Mayo,
Gadi Cohen Rappaport,
Melvin McInnis,
Uri Alon
Affiliations
Tomer Milo
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Lior Maimon
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Ben Cohen
Merchavim Mental Health Center, P.O.Box 1, Beer Yaakov 70350, Israel; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
Dafna Haran
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Dror Segman
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Tamar Danon
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Anat Bren
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Avi Mayo
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Gadi Cohen Rappaport
Merchavim Mental Health Center, P.O.Box 1, Beer Yaakov 70350, Israel; Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
Melvin McInnis
Heinz C Prechter Bipolar Research Program, Eisenberg Family Depression Center, Ann Arbor, MI, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
Uri Alon
Department Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Corresponding author
Summary: Bipolar disorder (BD) is marked by fluctuating mood states over months to years, often with elevated cortisol levels. Elevated cortisol can also trigger mood episodes. Here, we combine longitudinal hair cortisol and mood measurements with mathematical modeling to provide a potential mechanistic link between cortisol and mood timescales in BD. Using 12 cm hair samples, representing a year of growth, we found enhanced year-scale cortisol fluctuations whose amplitude averaged 4-fold higher in BD (n = 26) participants than controls (n = 59). The proximal 2 cm of hair correlated with recent mood scores. Depression (n = 266) and mania (n = 273) scores from a longitudinal study of BD showed similar frequency spectra. These results suggest a mechanism for BD in which high emotional reactivity excites the slow timescales in the hypothalamic–pituitary–adrenal (HPA) axis to generate elevated months-scale cortisol fluctuations, triggering cortisol-induced mood episodes.
