Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Addict Biol. 2021 Jan;26(1):e12835. doi: 10.1111/adb.12835. Epub 2019 Nov 8.
Fear conditioning and extinction (FCE) are vital processes in adaptive emotion regulation and disrupted in anxiety disorders. Despite substantial comorbidity between alcohol dependence (ALC) and anxiety disorders and reports of altered negative emotion processing in ALC, neural correlates of FCE in this clinical population remain unknown. Here, we used a 2-day fear learning paradigm in 43 healthy participants and 43 individuals with ALC at the National Institutes of Health. Main outcomes of this multimodal study included structural and functional brain magnetic resonance imaging, clinical measures, as well as skin conductance responses (SCRs) to confirm differential conditioning. Successful FCE was demonstrated across participants by differential SCRs in the conditioning phase and no difference in SCRs to the conditioned stimuli in the extinction phase. The ALC group showed significantly reduced blood oxygenation level-dependent responses in the right amygdala during conditioning (Cohen's d = .89, P = .037) and in the left amygdala during fear renewal (Cohen's d = .68, P = .039). Right amygdala activation during conditioning was significantly correlated with ALC severity (r = .39, P = .009), depressive symptoms (r = .37, P = .015), trait anxiety (r = .41, P = .006), and perceived stress (r = .45, P = .002). Our data suggest that individuals with ALC have dysregulated fear learning, in particular, dysregulated neural activation patterns, in the amygdala. Furthermore, amygdala activation during fear conditioning was associated with ALC-related clinical measures. The FCE paradigm may be a promising tool to investigate structures involved in negative affect regulation, which might inform the development of novel treatment approaches for ALC.
恐惧条件反射和消退（FCE）是适应性情绪调节的重要过程，在焦虑障碍中受到干扰。尽管酒精依赖（ALC）和焦虑障碍之间存在大量共病，并且有报道称 ALC 存在负面情绪处理改变，但在该临床人群中，FCE 的神经相关性仍不清楚。在这里，我们在国立卫生研究院使用了为期两天的恐惧学习范式，共纳入 43 名健康参与者和 43 名 ALC 患者。该多模态研究的主要结果包括结构和功能磁共振成像、临床测量以及皮肤电反应（SCR），以确认差异条件作用。通过在条件作用阶段中 SCR 的差异和在消退阶段中对条件刺激的 SCR 无差异，证明了所有参与者均成功完成了 FCE。在条件作用期间，ALC 组右侧杏仁核的血氧水平依赖反应显著降低（Cohen's d =.89，P =.037），在恐惧更新期间左侧杏仁核的血氧水平依赖反应也显著降低（Cohen's d =.68，P =.039）。在条件作用期间，右侧杏仁核的激活与 ALC 严重程度（r =.39，P =.009）、抑郁症状（r =.37，P =.015）、特质焦虑（r =.41，P =.006）和感知压力（r =.45，P =.002）显著相关。我们的数据表明，ALC 患者的恐惧学习失调，特别是杏仁核中的神经激活模式失调。此外，在恐惧条件作用期间杏仁核的激活与与 ALC 相关的临床测量指标相关。FCE 范式可能是一种有前途的工具，可用于研究参与负面情绪调节的结构，这可能为 ALC 的新型治疗方法的开发提供信息。
