Department of Psychiatry, University of Cambridge, Cambridge, UK.
Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
Psychol Med. 2022 Oct;52(14):3280-3288. doi: 10.1017/S0033291720005450. Epub 2021 Feb 11.
Risk is an essential trait of most daily decisions. Our behaviour when faced with risks involves evaluation of many factors including the outcome probabilities, the valence (gains or losses) and past experiences. Several psychiatric disorders belonging to distinct diagnostic categories, including pathological gambling and addiction, show pathological risk-taking and implicate abnormal dopaminergic, opioidergic and serotonergic neurotransmission. In this study, we adopted a transdiagnostic approach to delineate the neurochemical substrates of decision making under risk.
We recruited 39 participants, including 17 healthy controls, 15 patients with pathological gambling and seven binge eating disorder patients, who completed an anticipatory risk-taking task. Separately, participants underwent positron emission tomography (PET) imaging with three ligands, [F]fluorodopa (FDOPA), [C]MADAM and [C]carfentanil to assess presynaptic dopamine synthesis capacity and serotonin transporter and mu-opioid receptor binding respectively.
Risk-taking behaviour when faced with gains positively correlated with dorsal cingulate [C]carfentanil binding and risk-taking to losses positively correlated with [C]MADAM binding in the caudate and putamen across all subjects.
We show distinct neurochemical substrates underlying risk-taking with the dorsal cingulate cortex mu-opioid receptor binding associated with rewards and dorsal striatal serotonin transporter binding associated with losses. Risk-taking and goal-directed control appear to dissociate between dorsal and ventral fronto-striatal systems. Our findings thus highlight the potential role of pharmacological agents or neuromodulation on modifying valence-specific risk-taking biases.
风险是大多数日常决策的基本特征。当我们面对风险时，我们的行为涉及到对许多因素的评估，包括结果的概率、价值（收益或损失）和过去的经验。几种属于不同诊断类别的精神疾病，包括病理性赌博和成瘾，表现出病理性的冒险行为，并暗示异常的多巴胺能、阿片能和 5-羟色胺能神经传递。在这项研究中，我们采用了一种跨诊断的方法来描绘风险决策的神经化学基础。
我们招募了 39 名参与者，包括 17 名健康对照者、15 名病理性赌博患者和 7 名暴食症患者，他们完成了一项预期风险承担任务。此外，参与者分别接受了正电子发射断层扫描（PET）成像，使用三种配体 [F]氟多巴（FDOPA）、[C]MADAM 和 [C]卡芬太尼，以评估前扣带皮质的多巴胺合成能力以及 5-羟色胺转运体和 μ-阿片受体结合。
面对收益的冒险行为与背侧扣带 [C]卡芬太尼结合呈正相关，面对损失的冒险行为与尾状核和壳核中的 [C]MADAM 结合呈正相关，所有受试者均如此。
我们展示了冒险行为的不同神经化学基础，背侧扣带皮质 μ-阿片受体结合与奖励有关，而背侧纹状体 5-羟色胺转运体结合与损失有关。冒险行为和目标导向控制似乎在背侧和腹侧额纹状体系统之间分离。因此，我们的发现强调了药理学药物或神经调节在改变效价特异性冒险行为偏倚方面的潜在作用。
