Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression
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Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression. / Macoveanu, J; Knorr, U; Skimminge, A; Greisen Søndergaard, Mia; Jørgensen, Anders; Fauerholdt-Jepsen, M; Paulson, O B; Knudsen, Gitte M.; Siebner, H R; Kessing, L V.
In: Psychological Medicine, Vol. 44, No. 6, 04.2014, p. 1183-95.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression
AU - Macoveanu, J
AU - Knorr, U
AU - Skimminge, A
AU - Greisen Søndergaard, Mia
AU - Jørgensen, Anders
AU - Fauerholdt-Jepsen, M
AU - Paulson, O B
AU - Knudsen, Gitte M.
AU - Siebner, H R
AU - Kessing, L V
PY - 2014/4
Y1 - 2014/4
N2 - BACKGROUND: Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.METHOD: In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD-). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.RESULTS: Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.CONCLUSIONS: Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.
AB - BACKGROUND: Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.METHOD: In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD-). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.RESULTS: Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.CONCLUSIONS: Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.
KW - Adult
KW - Citalopram
KW - Depressive Disorder, Major
KW - Double-Blind Method
KW - Family
KW - Female
KW - Genetic Predisposition to Disease
KW - Hippocampus
KW - Humans
KW - Magnetic Resonance Imaging
KW - Male
KW - Placebos
KW - Prefrontal Cortex
KW - Reward
KW - Serotonin Uptake Inhibitors
KW - Treatment Outcome
U2 - 10.1017/S0033291713001815
DO - 10.1017/S0033291713001815
M3 - Journal article
C2 - 23866315
VL - 44
SP - 1183
EP - 1195
JO - Psychological Medicine
JF - Psychological Medicine
SN - 0033-2917
IS - 6
ER -
ID: 138501684