Clinical Psychology Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, 08907, Barcelona, Spain.
Ciber Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 08907, Barcelona, Spain.
Mol Psychiatry. 2023 Nov;28(11):4793-4800. doi: 10.1038/s41380-023-02253-2. Epub 2023 Sep 28.
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; p < 0.001) and the left supplementary motor area (NAcc-SMA; p < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.
神经性厌食症（AN）是一种严重的精神疾病，其特征是有害地坚持自我饥饿导致显著的体重减轻。研究表明，伏隔核（NAcc）和循环内源性大麻素（eCBs）的改变，如花生四烯酸乙醇胺（AEA）和 2-花生四烯酸甘油（2-AG），可能导致 AN 中严重程度的增加和适应不良行为，这需要检查中枢奖励回路和 eCBs 之间的相互作用。为此，我们评估了 18 名 AN 患者和 18 名健康对照者（HC）的 NAcc 功能连接和循环 AEA 和 2-AG 浓度，以测试循环 eCBs、NAcc 功能连接与 AN 严重程度之间的关联，AN 严重程度由体重指数（BMI）定义。与 HC 相比，AN 组中 NAcc 与右侧脑岛（NAcc-insula；p < 0.001）和左侧辅助运动区（NAcc-SMA；p < 0.001）之间的连接减少。在 AN 组中，NAcc-insula 功能连接的减少介导了 AEA 浓度与 BMI 之间的关联。然而，在 HC 中，NAcc-SMA 功能连接在 AEA 浓度与 BMI 之间具有中介作用。尽管两组之间没有观察到 eCBs 浓度的显著差异，但我们的研究结果提供了有关内源性大麻素和 NAcc 功能连接相互作用如何影响 AN 严重程度的见解。AN 中 NAcc-insula 和 NAcc-SMA 连接的改变可能会损害与奖励刺激相关的内脏感觉、躯体感觉和运动计划信息的整合。此外，AN 和 HC 中 eCBs 浓度与 NAcc 功能连接之间的不同关联可能对体重维持具有临床意义，内源性大麻素可能成为 AN 治疗的潜在靶点。
