Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression

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 - 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.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.

AB - 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.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.

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

SN - 0033-2917

VL - 44

SP - 1183

EP - 1195

JO - Psychological Medicine

JF - Psychological Medicine

IS - 6

ER -