title: Testosterone and reward prediction-errors in healthy men and men with schizophrenia.
abstract: Sex hormones impact reward processing, which is dysfunctional in schizophrenia; however, the degree to which testosterone levels relate to reward-related brain activity in healthy men and the extent to which this relationship may be altered in men with schizophrenia has not been determined. We used functional magnetic resonance imaging (fMRI) to measure neural responses in the striatum during reward prediction-errors and hormone assays to measure testosterone and prolactin in serum. To determine if testosterone can have a direct effect on dopamine neurons, we also localized and measured androgen receptors in human midbrain with immunohistochemistry and quantitative PCR. We found correlations between testosterone and prediction-error related activity in the ventral striatum of healthy men, but not in men with schizophrenia, such that testosterone increased the size of positive and negative prediction-error related activity in a valence-specific manner. We also identified midbrain dopamine neurons that were androgen receptor immunoreactive, and found that androgen receptor (AR) mRNA was positively correlated with tyrosine hydroxylase (TH) mRNA in human male substantia nigra. The results suggest that sex steroid receptors can potentially influence midbrain dopamine biosynthesis, and higher levels of serum testosterone are linked to better discrimination of motivationally-relevant signals in the ventral striatum, putatively by modulation of the dopamine biosynthesis pathway via AR ligand binding. However, the normal relationship between serum testosterone and ventral striatum activity during reward learning appears to be disrupted in schizophrenia.
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, New South Wales 2031, Australia; Schizophrenia Research Institute, Liverpool St, Darlinghurst, New South Wales 2010, Australia; School of Psychiatry, University of New South Wales, Hospital Rd, New South Wales 2031, Australia.
authors.forename: R W
authors.initials: RW
authors.lastname: Morris
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, New South Wales 2031, Australia; Schizophrenia Research Institute, Liverpool St, Darlinghurst, New South Wales 2010, Australia; School of Medical Sciences, University of New South Wales, New South Wales 2031, Australia.
authors.forename: T D
authors.initials: TD
authors.lastname: Purves-Tyson
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, New South Wales 2031, Australia; Schizophrenia Research Institute, Liverpool St, Darlinghurst, New South Wales 2010, Australia; School of Psychiatry, University of New South Wales, Hospital Rd, New South Wales 2031, Australia.
authors.forename: C Shannon
authors.initials: CS
authors.lastname: Weickert
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, New South Wales 2031, Australia; Schizophrenia Research Institute, Liverpool St, Darlinghurst, New South Wales 2010, Australia; School of Psychiatry, University of New South Wales, Hospital Rd, New South Wales 2031, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Rothmond
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, New South Wales 2031, Australia; Schizophrenia Research Institute, Liverpool St, Darlinghurst, New South Wales 2010, Australia; School of Psychiatry, University of New South Wales, Hospital Rd, New South Wales 2031, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Lenroot
authors.affiliation: Neuroscience Research Australia, Barker St, Randwick, New South Wales 2031, Australia; Schizophrenia Research Institute, Liverpool St, Darlinghurst, New South Wales 2010, Australia; School of Psychiatry, University of New South Wales, Hospital Rd, New South Wales 2031, Australia. Electronic address: t.weickert@unsw.edu.au.
authors.forename: T W
authors.initials: TW
authors.lastname: Weickert
mesh_terms: D000328:Adult; D059031:Anticipation, Psychological / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002908:Chronic Disease; D015331:Cohort Studies; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011618:Psychotic Disorders / Q000503:physiopathology / Q000523:psychology; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012201:Reward; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013739:Testosterone / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D014446:Tyrosine 3-Monooxygenase; D010100:Oxygen
keywords: Androgen receptor; Associative learning; Midbrain; Postmortem; Reward; Schizophrenia; Sex hormones; Testosterone; Tyrosine hydroxylase; Ventral striatum