杏仁核、前扣带回皮层和岛叶活动亢进被认为是其发病机制。这一理论基于通过循证暴露疗法后发现这些区域的特异性神经活动显著减少。[21]Goossens L, Sunaert S, Peeters R, et al. Amygdala hyperfunction in phobic fear normalizes after exposure. Biol Psychiatry. 2007;62:1119-1125.http://www.ncbi.nlm.nih.gov/pubmed/17706612?tool=bestpractice.com神经影像学研究表明在接触恐怖症相关的刺激时杏仁核激活增加,丘脑、岛叶和背侧前扣带脑皮质区域的活性增强。[22]Straube T, Mentzel HJ, Miltner WH. Neural mechanisms of automatic and direct processing of phobogenic stimuli in specific phobia. Biol Psychiatry. 2006;59:162-170.http://www.ncbi.nlm.nih.gov/pubmed/16139812?tool=bestpractice.com[23]Schienle A, Schafer A, Walter B, et al. Brain activation of spider phobics towards disorder-relevant, generally disgust- and fear-inducing pictures. Neurosci Lett. 2005;388:1-6.http://www.ncbi.nlm.nih.gov/pubmed/16046064?tool=bestpractice.com[21]Goossens L, Sunaert S, Peeters R, et al. Amygdala hyperfunction in phobic fear normalizes after exposure. Biol Psychiatry. 2007;62:1119-1125.http://www.ncbi.nlm.nih.gov/pubmed/17706612?tool=bestpractice.com[24]Straube T, Mentzel HJ, Miltner WH. Waiting for spiders: brain activation during anticipatory anxiety in spider phobics. Neuroimage. 2007;37:1427-1436.http://www.ncbi.nlm.nih.gov/pubmed/17681799?tool=bestpractice.com[25]Damsa C, Kosel M, Moussally J, et al. Current status of brain imagining in anxiety disorders. Curr Op Psychiatry. 2009;22:96-110.http://www.ncbi.nlm.nih.gov/pubmed/19122541?tool=bestpractice.comMeta 分析表明,恐怖症组与非恐怖症对照组相比,当暴露于恐惧相关的刺激时,左侧杏仁核/苍白球、左侧岛叶、右侧丘脑和小脑部位全都更加活跃;以暴露为基础的治疗导致右额叶皮质、边缘皮层、基底节和小脑活动增强现象消失,而丘脑的活动性增加。[26]Ipser JC, Singh L, Stein DJ. Meta-analysis of functional brain imaging in specific phobia. Psychiatry Clin Neurosci. 2013;67:311-322.http://www.ncbi.nlm.nih.gov/pubmed/23711114?tool=bestpractice.com在一个小型的混合类型恐怖症患者样本中观察到当暴露威胁期间,P物质-神经激肽1受体占有率增加(尤其在右侧杏仁核)。[27]Michelgard A, Appel L, Pissiota A, et al. Symptom provocation in specific phobia affects substance P neurokinin-1 receptor system. Biol Psychiatry. 2007;61:1002-1006.http://www.ncbi.nlm.nih.gov/pubmed/16950220?tool=bestpractice.com
脑功能成像研究已经明确恐怖症的相关神经结构参与模式不同于其他焦虑障碍,各种恐怖症亚型中激活的模式也不同。[28]Del Casale A, Ferracuti S, Rapinesi C, et al. Functional neuroimaging in specific phobia. Psychiatry Res. 2012;202:181-197.http://www.ncbi.nlm.nih.gov/pubmed/22804970?tool=bestpractice.com
在暴露于刺激物时出现的急性的、明显的副交感神经系统活动被认为是血管迷走性晕厥的原因,多达80%血液注射损伤型恐惧症受此困扰。[29]Ost LG. Blood and injection phobia: background and cognitive, physiological, and behavioral variables. J Abnorm Psychol. 1992;101:68-74.http://www.ncbi.nlm.nih.gov/pubmed/1537975?tool=bestpractice.com[30]Page AC. The role of disgust in faintness elicited by blood and injection stimuli. J Anxiety Disord. 2003;17:45-58.http://www.ncbi.nlm.nih.gov/pubmed/12464288?tool=bestpractice.com