Macoveanu J, Knorr U, Skimminge A, Søndergaard M G, Jørgensen A, Fauerholdt-Jepsen M, Paulson O B, Knudsen G M, Siebner H R, Kessing L V
Danish Research Center for Magnetic Resonance, Hvidovre Hospital, Copenhagen University Hospital, Denmark.
Psychiatric Center Copenhagen, Rigshospitalet, Copenhagen University Hospital, Denmark.
Psychol Med. 2014 Apr;44(6):1183-95. doi: 10.1017/S0033291713001815. Epub 2013 Jul 19.
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.
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.
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.
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.
重度抑郁症患者（rMD+）的健康一级亲属表现出脑结构和功能反应异常，且患抑郁症的风险增加，抑郁症是一种与血清素能神经传递和奖赏处理异常有关的疾病。
在一项分两步进行的功能磁共振成像（fMRI）研究中，我们首先评估了与对照先证者的健康一级亲属（rMD-）相比，rMD+个体对正向和负向金钱结果的处理是否存在差异。其次，在一项双盲安慰剂对照随机试验中，我们研究了选择性血清素再摄取抑制剂（SSRI）艾司西酞普兰进行为期4周的干预是否对rMD+个体的行为和脑反应具有正常化作用。
负向结果增加了rMD+个体而非rMD-个体在后续试验中做出规避风险选择的概率。与rMD-组相比，rMD+组中当受试者在低风险选择后错过大额奖赏时，眶额皮质（OFC）表现出更强的神经反应。与安慰剂相比，艾司西酞普兰干预后，眶额皮质对负向结果增强的反应得到逆转。相反，对于正向结果，与rMD-组相比，rMD+组左侧海马体对高额赢钱的反应减弱。SSRI干预增强了海马体对大额赢钱的反应。随后的结构分析表明，rMD+个体灰质密度的变化并不能解释异常的神经反应。
我们对抑郁症患者一级亲属的研究表明，在已知与抑郁症功能失调相关的区域，大脑对厌恶和奖赏结果存在异常反应。我们进一步证实了SSRI干预可逆转这些异常激活。
