Nicotine dependence and major depressive disorder (MDD) are highly comorbid, yet causal links between these prevalent disorders are unclear. One possible mechanism is that nicotine ameliorates MDD-related neurobiological dysfunction in specific networks. For instance, cortico-striatal circuitry is enhanced by nicotine, and such paths are disrupted in individuals with MDD. Specifically, MDD has been associated with reduced connectivity between the nucleus accumbens (NAc) and rostral anterior cingulate cortex (rACC) but enhanced connectivity between the dorsal striatum (DS) and dorsolateral prefrontal cortex (DLPFC). Determining whether nicotine normalizes these circuits in non-smokers with MDD may elucidate mechanisms underlying links between disorders. This was tested by administering placebo and a 2-mg dose of nicotine to unmedicated non-smokers with and without MDD prior to collecting resting-state functional magnetic imaging data using a cross-over design. On placebo, individuals with MDD showed significantly reduced NAc-rACC and a trend for enhanced DS-DLPFC functional connectivity relative to healthy controls. In MDD, acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. Nicotine's effects on NAc-rACC connectivity was influenced by anhedonia, consistent with the role of this network in reward and nicotine's ability to enhance reward deficiencies in MDD. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD. Nicotine's influence on these circuitries highlights a possible mechanism whereby individuals with MDD are more vulnerable to develop nicotine dependence. Findings suggest that nicotinic agents may have therapeutic effects on disrupted cortico-striatal connectivity.

中文翻译：

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尼古丁可使患有严重抑郁症的非吸烟者的皮质-纹状体连接正常化。

尼古丁依赖性和重度抑郁症（MDD）高度合并，但这些流行性疾病之间的因果关系尚不清楚。一种可能的机制是尼古丁改善了特定网络中与MDD相关的神经生物学功能障碍。例如，尼古丁增强了皮质-纹状体的回路，并且这种路径在患有MDD的个体中被破坏。特别地，MDD与伏伏核（NAc）和前额扣带回皮层（rACC）之间的连通性降低，但背侧纹状体（DS）和背外侧前额叶皮层（DLPFC）之间的连通性增强有关。确定尼古丁是否使患有MDD的非吸烟者的这些回路正常化，可以阐明潜在的疾病之间联系的机制。通过使用交叉设计在收集静止状态功能磁成像数据之前，通过在有或没有MDD的情况下，对未服用药物的非吸烟者使用安慰剂和2 mg烟碱进行测试。在安慰剂上，相对于健康对照组，患有MDD的个体表现出NAc-rACC显着降低，并且DS-DLPFC功能连接性增强。在MDD中，急性尼古丁给药可将两种途径归一化为健康对照水平，而对健康对照无影响。烟碱对尼古丁对NAc-rACC连接性的影响受到影响，这与该网络在奖励中的作用以及尼古丁增强MDD奖励不足的能力相一致。这些结果表明，尼古丁可使患有MDD的非药物非吸烟者的皮质-纹状体功能障碍正常化。尼古丁' 对这些回路的影响突显了一种可能的机制，MDD患者更容易发展出对尼古丁的依赖性。研究结果表明，烟碱类药物可能对破坏的皮层纹状体连通性有治疗作用。