Macoveanu Julian, Meluken Iselin, Chase Henry W, Phillips Mary L, Kessing Lars Vedel, Siebner Hartwig Roman, Vinberg Maj, Miskowiak Kamilla W
Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Psychol Med. 2021 Jul;51(10):1637-1646. doi: 10.1017/S0033291720000367. Epub 2020 Mar 2.
Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders.
In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25).
Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions.
Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders.
单相(UD)和双相(BD)障碍中经历的抑郁发作以快感缺失为特征,并与奖励评估和错误预测相关的奖励过程异常有关。然而,这些缺陷是否与情绪障碍的家族易感性相关仍不清楚。
在一项功能磁共振成像研究中,我们评估了三组同卵双胞胎腹侧纹状体(VS)和前额叶皮质中预期价值(EV)和奖励预测误差(RPE)信号的差异:UD或BD缓解期的患病双胞胎(n = 53)、其高风险未患病的同卵双胞胎(n = 34)以及无情绪障碍家族史的低风险双胞胎(n = 25)。
与低风险双胞胎相比,患病双胞胎双侧额极的EV信号较低,双侧VS、左侧额极和额上回的RPE信号较低。高风险组在额纹状体区域的EV或RPE信号没有显著变化,但在患病双胞胎显示显著降低的所有区域,与低风险双胞胎相比,这两种奖励信号始终较低。
我们的研究结果强化了这样一种观点,即预期奖励的评估降低和错误依赖的奖励学习减少可能是抑郁症核心症状(如对奖励活动失去兴趣)的基础。未患病同卵双胞胎中奖励相关信号的下降趋势值得在更大样本中进一步研究这种效应,并进行前瞻性随访,以确认可能与情绪障碍家族易感性增加的关联。