Christina M Hough1, Daniel Lindqvist2, Elissa S Epel1, Molly St Denis1, Victor I Reus1, F Saverio Bersani3, Rebecca Rosser1, Laura Mahan1, Heather M Burke1, Owen M Wolkowitz1, Synthia H Mellon4. 1. Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. 2. Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden. 3. Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. 4. Department of OB/GYN and Reproductive Sciences, UCSF School of Medicine, San Francisco, 513 Parnassus Ave., San Francisco, CA 94143-0556, USA. Electronic address: Sindy.Mellon@ucsf.edu.
Abstract
BACKGROUND: Dehydroepiandrosterone (DHEA) and its sulfated ester DHEA-sulfate (DHEA-S), (together DHEA[S]), are the most abundant adrenal steroids in humans and are found in blood and the brain, where they function as neurosteroids with direct receptor affinities. Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear. METHODS: Morning fasting serum DHEA(S) concentrations were determined in 36 healthy, unmedicated MDD adults with Hamilton Depression (HDRS) ratings ≥17, and 75 healthy controls. MDD participants then completed eight weeks of open-label SSRI treatment before DHEA(S) levels were re-sampled; those with post-treatment HDRS ratings ≤7 were classified as "Remitters." Pre- and post-treatment DHEA(S) levels of Remitters and Non-remitters were compared, controlling for age, sex, and BMI. RESULTS: Pre-treatment HDRS ratings did not differ between Remitters and Non-remitters (p=0.179). Baseline DHEA levels of Remitters were significantly higher than both Non-remitters (p=0.008) and controls (p=0.004); baseline DHEA-S levels of Remitters were also higher than Non-remitters (p=0.040) but did not significantly differ from controls (p=0.096). Non-remitters did not significantly differ from controls. Post-treatment DHEA(S) levels remained higher in Remitters compared to Non-remitters (DHEA: p=0.013; DHEA-S: p=0.040). CONCLUSIONS: These data suggest that higher circulating DHEA(S) levels (while unmedicated and after eight weeks of SSRI treatment) predict SSRI-associated remission in MDD. This raises the possibility that endogenous DHEA(S) abundance is a physiological adjunct to SSRI efficacy, as suggested by prior preclinical and clinical studies.
BACKGROUND:Dehydroepiandrosterone (DHEA) and its sulfated esterDHEA-sulfate (DHEA-S), (together DHEA[S]), are the most abundant adrenal steroids in humans and are found in blood and the brain, where they function as neurosteroids with direct receptor affinities. Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear. METHODS: Morning fasting serum DHEA(S) concentrations were determined in 36 healthy, unmedicated MDD adults with Hamilton Depression (HDRS) ratings ≥17, and 75 healthy controls. MDDparticipants then completed eight weeks of open-label SSRI treatment before DHEA(S) levels were re-sampled; those with post-treatment HDRS ratings ≤7 were classified as "Remitters." Pre- and post-treatment DHEA(S) levels of Remitters and Non-remitters were compared, controlling for age, sex, and BMI. RESULTS: Pre-treatment HDRS ratings did not differ between Remitters and Non-remitters (p=0.179). Baseline DHEA levels of Remitters were significantly higher than both Non-remitters (p=0.008) and controls (p=0.004); baseline DHEA-S levels of Remitters were also higher than Non-remitters (p=0.040) but did not significantly differ from controls (p=0.096). Non-remitters did not significantly differ from controls. Post-treatment DHEA(S) levels remained higher in Remitters compared to Non-remitters (DHEA: p=0.013; DHEA-S: p=0.040). CONCLUSIONS: These data suggest that higher circulating DHEA(S) levels (while unmedicated and after eight weeks of SSRI treatment) predict SSRI-associated remission in MDD. This raises the possibility that endogenous DHEA(S) abundance is a physiological adjunct to SSRI efficacy, as suggested by prior preclinical and clinical studies.
Authors: Madhukar H Trivedi; A John Rush; Stephen R Wisniewski; Andrew A Nierenberg; Diane Warden; Louise Ritz; Grayson Norquist; Robert H Howland; Barry Lebowitz; Patrick J McGrath; Kathy Shores-Wilson; Melanie M Biggs; G K Balasubramani; Maurizio Fava Journal: Am J Psychiatry Date: 2006-01 Impact factor: 18.112
Authors: O M Wolkowitz; V I Reus; A Keebler; N Nelson; M Friedland; L Brizendine; E Roberts Journal: Am J Psychiatry Date: 1999-04 Impact factor: 18.112
Authors: T J Fabian; M A Dew; B G Pollock; C F Reynolds; B H Mulsant; M A Butters; M D Zmuda; A M Linares; M Trottini; P D Kroboth Journal: Biol Psychiatry Date: 2001-11-15 Impact factor: 13.382
Authors: Peter J Schmidt; Robert C Daly; Miki Bloch; Mark J Smith; Merry A Danaceau; Linda Simpson St Clair; Jean H Murphy; Nazli Haq; David R Rubinow Journal: Arch Gen Psychiatry Date: 2005-02
Authors: M Takebayashi; A Kagaya; Y Uchitomi; A Kugaya; M Muraoka; N Yokota; J Horiguchi; S Yamawaki Journal: J Neural Transm (Vienna) Date: 1998 Impact factor: 3.575
Authors: E Romeo; A Ströhle; G Spalletta; F di Michele; B Hermann; F Holsboer; A Pasini; R Rupprecht Journal: Am J Psychiatry Date: 1998-07 Impact factor: 18.112
Authors: A John Rush; Madhukar H Trivedi; Stephen R Wisniewski; Jonathan W Stewart; Andrew A Nierenberg; Michael E Thase; Louise Ritz; Melanie M Biggs; Diane Warden; James F Luther; Kathy Shores-Wilson; George Niederehe; Maurizio Fava Journal: N Engl J Med Date: 2006-03-23 Impact factor: 91.245
Authors: Melinda L Morgan; Andrea J Rapkin; Giovanni Biggio; Mariangela Serra; Maria Giuseppina Pisu; Natalie Rasgon Journal: Arch Womens Ment Health Date: 2009-09-03 Impact factor: 3.633
Authors: Felipe A Jain; Colm G Connolly; Victor I Reus; Dieter J Meyerhoff; Tony T Yang; Synthia H Mellon; Scott Mackin; Christina M Hough; Alexandra Morford; Owen M Wolkowitz Journal: Psychoneuroendocrinology Date: 2019-07-26 Impact factor: 4.905
Authors: Carlos Alfonso Tovilla-Zárate; Antonia Pérez-Mandujano; Iris Rubí Ramírez-González; Ana Fresan; Samuel Suarez-Mendez; Esteban Martínez-Villaseñor; Ester Rodríguez-Sánchez; Mario Villar-Soto; María Lilia López-Narváez; Thelma Beatriz González-Castro; Jorge L Ble-Castillo; Isela Esther Juárez-Rojop Journal: Ann Transl Med Date: 2019-11
Authors: Angela L Cumberland; Jonathan J Hirst; Emilio Badoer; Stefan A Wudy; Ronda F Greaves; Margaret Zacharin; David W Walker Journal: Int J Mol Sci Date: 2021-04-21 Impact factor: 5.923