title: DHEA enhances emotion regulation neurocircuits and modulates memory for emotional stimuli.
abstract: Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA. rekaufma@umich.edu
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Sripada
authors.forename: Christine E
authors.initials: CE
authors.lastname: Marx
authors.forename: Anthony P
authors.initials: AP
authors.lastname: King
authors.forename: Nirmala
authors.initials: N
authors.lastname: Rajaram
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Garfinkel
authors.forename: James L
authors.initials: JL
authors.lastname: Abelson
authors.forename: Israel
authors.initials: I
authors.lastname: Liberzon
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000097:blood / Q000494:pharmacology*
chemical_list: D018377:Neurotransmitter Agents; D003687:Dehydroepiandrosterone
references.citation: Neuropsychopharmacology. 2004 Aug;29(8):1546-57
references.pmid: 15199367
references.citation: Psychopharmacology (Berl). 2006 Jun;186(3):462-72
references.pmid: 16402195
references.citation: Pharmacol Biochem Behav. 1994 Mar;47(3):437-41
references.pmid: 7911573
references.citation: J Clin Endocrinol Metab. 1998 Jun;83(6):1928-34
references.pmid: 9626121
references.citation: Am J Psychiatry. 2007 Oct;164(10):1476-88
references.pmid: 17898336
references.citation: Ann N Y Acad Sci. 2010 Oct;1208:158-63
references.pmid: 20955338
references.citation: Arch Gen Psychiatry. 2005 Feb;62(2):154-62
references.pmid: 15699292
references.citation: Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):1062-78
references.pmid: 17928160
references.citation: Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):874-83
references.pmid: 17651906
references.citation: Asian J Androl. 2011 Nov;13(6):898-902
references.pmid: 21874029
references.citation: Psychopharmacology (Berl). 2006 Jun;186(3):434-41
references.pmid: 16052364
references.citation: Exp Biol Med (Maywood). 2010 Oct;235(10):1150-62
references.pmid: 20881319
references.citation: Neuropsychopharmacology. 2000 Nov;23(5):508-16
references.pmid: 11027916
references.citation: Neuro Endocrinol Lett. 2011;32(4):442-8
references.pmid: 21876493
references.citation: J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
references.pmid: 9881538
references.citation: Clin Endocrinol (Oxf). 1998 Oct;49(4):421-32
references.pmid: 9876338
references.citation: Behav Brain Res. 2000 Jun 1;110(1-2):97-108
references.pmid: 10802307
references.citation: Psychiatry Res. 1994 Jan;51(1):19-31
references.pmid: 8197269
references.citation: Psychol Med. 2000 Sep;30(5):1227-31
references.pmid: 12027057
references.citation: J Clin Psychiatry. 2006 Mar;67(3):493-6
references.pmid: 16649840
references.citation: Emotion. 2001 Mar;1(1):70-83
references.pmid: 12894812
references.citation: Neuropsychopharmacology. 2000 Jul;23(1):69-78
references.pmid: 10869887
references.citation: J Clin Psychopharmacol. 2006 Oct;26(5):495-9
references.pmid: 16974191
references.citation: J Neurosci. 2003 Jul 2;23(13):5627-33
references.pmid: 12843265
references.citation: Neuropsychopharmacology. 2008 Jan;33(1):56-72
references.pmid: 17882236
references.citation: Front Neuroendocrinol. 2009 Jan;30(1):65-91
references.pmid: 19063914
references.citation: Brain Res. 2009 Sep 15;1289:22-9
references.pmid: 19595679
references.citation: Neuroimage. 2004 Feb;21(2):768-80
references.pmid: 14980580
references.citation: Behav Neurosci. 1997 Jun;111(3):512-7
references.pmid: 9189266
references.citation: Acta Neurobiol Exp (Wars). 2012;72(1):65-79
references.pmid: 22508085
references.citation: Biol Psychiatry. 2013 Jun 1;73(11):1045-53
references.pmid: 23348009
references.citation: Neuroscience. 2011 Sep 15;191:22-7
references.pmid: 21641969
references.citation: Neuropsychologia. 2011 Mar;49(4):695-705
references.pmid: 21414466
references.citation: Proc Soc Exp Biol Med. 1999 Nov;222(2):145-9
references.pmid: 10564538
references.citation: J Clin Endocrinol Metab. 2008 Aug;93(8):3173-8
references.pmid: 18477662
references.citation: Biol Psychol. 2012 Feb;89(2):293-9
references.pmid: 22115881
references.citation: Psychiatry Res. 1997 Dec 30;76(2-3):75-82
references.pmid: 9522399
references.citation: Emotion. 2008 Jun;8(3):307-17
references.pmid: 18540747
references.citation: Biol Psychiatry. 2001 Aug 15;50(4):238-45
references.pmid: 11522257
references.citation: J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):385-90
references.pmid: 15860479
references.citation: Am J Psychiatry. 1999 Apr;156(4):646-9
references.pmid: 10200751
references.citation: Neuroreport. 1998 Sep 14;9(13):3069-73
references.pmid: 9804318
references.citation: Emotion. 2011 Jun;11(3):468-80
references.pmid: 21534661
references.citation: Biol Psychiatry. 1999 Jun 15;45(12):1533-41
references.pmid: 10376113
references.citation: Neuroimage. 2011 Feb 1;54(3):2503-13
references.pmid: 20946960
references.citation: Arch Gen Psychiatry. 2006 Apr;63(4):450-6
references.pmid: 16585475
references.citation: J Steroid Biochem. 1987 Sep;28(3):317-25
references.pmid: 2958661
references.citation: Cogn Emot. 2012;26(2):282-99
references.pmid: 21806384
references.citation: Cochrane Database Syst Rev. 2006 Oct 18;(4):CD006221
references.pmid: 17054283
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4089-91
references.pmid: 9539693
references.citation: Nature. 2002 Nov 7;420(6911):70-4
references.pmid: 12422216
references.citation: Psychopharmacology (Berl). 2006 Nov;188(4):541-51
references.pmid: 16231168
references.citation: Epilepsia. 2005 Jun;46(6):819-27
references.pmid: 15946323
references.citation: J Clin Endocrinol Metab. 2008 Mar;93(3):801-8
references.pmid: 18073302
references.citation: J Am Geriatr Soc. 1999 Jun;47(6):685-91
references.pmid: 10366167
references.citation: Depress Anxiety. 2011 Mar;28(3):194-201
references.pmid: 21394852