抑郁障碍(Depressive Disorder)是全球最常见的精神障碍之一,其典型特征包括情感低落,思维迟缓、以及言语减少,动作迟缓,严重影响患者的生活质量(World Health Organization, 2023)。根据《美国精神病学协会》(American Psychiatric Association, 2022)的诊断标准,抑郁症的诊断需满足在至少两周内持续显现显著的情绪低落、注意力下降、自我价值感降低及自杀意念等症状。
近年来,嗅觉障碍与抑郁症之间的关系引起了广泛关注(
Kohli et al., 2016
),大量研究表明,二者之间存在显著的双向关联,且嗅觉功能与抑郁症状呈负相关。例如,抑郁症患者普遍表现出嗅觉敏感度的下降(
Lombion-Pouthier et al., 2006
;
Negoias et al., 2010
;
Pause et al., 2001
),嗅觉识别能力受损
(Croy et al., 2014b
;
Pentzek et al., 2007
),嗅觉辨别能力减退(
Atanasova et al., 2010
;
Croy et al., 2014c
),以及对气味的享乐感知能力的改变(
Naudin et al., 2014
)。嗅觉丧失和抑郁症之间的这种双向关系可能直接源于影响嗅觉和情感领域的中枢神经系统的改变,神经影像研究表明,抑郁症患者的嗅球体积显著缩小(
Negoias et al., 2016
),且与嗅觉处理相关的丘脑和眶额皮质的激活度降低(
Croy et al., 2014b
)。嗅觉障碍不仅影响神经系统,还可能通过多种机制加重抑郁症状。首先,嗅觉系统与大脑边缘系统(负责情感处理)的高度重叠,嗅觉输入的减少可能削弱边缘系统的活跃度,从而加剧情绪低落,并可能引发情感麻木(Anhedonia)——这是抑郁症的核心症状之一。此外,嗅觉障碍还可能通过影响日常生活中的关键方面,如饮食、安全感、社交互动和总体生活质量,从而加重抑郁症状(
Croy et al., 2014a
)。例如,嗅觉丧失的患者由于无法及时察觉变质食物或泄露气体等潜在危险,可能产生强烈的不安全感和焦虑;同时,他们可能因无法感知自身或他人的体味而感到尴尬,从而减少社交活动,导致社会隔离。此外,嗅觉与记忆密切相关,嗅觉丧失可能削弱与愉快记忆的联结,进而降低生活的幸福感,增加抑郁的风险(
Rochet et al., 2018
)。因此,嗅觉处理脑区的功能异常被认为可能与抑郁症的病理机制相关,嗅觉功能障碍作为抑郁症潜在的早期生物标志物逐渐受到研究者的重视。这些发现不仅有助于抑郁症的早期筛查,还可能为临床干预提供新的切入点。
嗅觉训练(Olfactory Training, OT)是一种非药物干预方法,通过系统性地嗅闻一组特定的气味(如玫瑰、柠檬、丁香气味等)来帮助患者恢复嗅觉功能。嗅觉训练通常要求患者每天两次嗅闻气味,持续12周左右,以反复的气味刺激来激活嗅觉神经通路,尤其是嗅球(Olfactory Bulb)和与情绪、记忆相关的大脑区域(如海马体和边缘系统)。由于嗅球信号直接投射到边缘系统,因此嗅觉训练可能不仅有助于嗅觉功能的恢复,还可能改善认知和情绪处理。一些研究表明,嗅觉训练除了可以有效改善嗅觉丧失患者的嗅觉功能之外,还会诱导积极,情绪提高被试的幸福感(
Hummel et al., 2009
;
Konstantinidis et al., 2013
)。众所周知,抑郁症状往往伴随着快速的享乐下降和积极情绪的缺失,这就引出了一项研究问题,嗅觉训练是否可被用于改善抑郁症状。
2. 嗅觉训练和抑郁症研究现状2.1. 文献筛选
为了探究上述问题,我们回顾了以往关于嗅觉训练影响抑郁症状的研究,从知网,万方,维普,Web of Science,pubmed五个数据库搜索文献,在英文文献库中搜索的词条包括:(Olfactory training [Title/Abstract]) AND (depression [Text Word]);在中文文献库中搜索词条包括:TKA = “嗅觉训练”AND TKA = “抑郁”。将所有潜在可用的研究都纳入第一步的文献筛选中。
<xref></xref>Table 1. Summary of studies on OT effectiveness including clinical samplesTable 1. Summary of studies on OT effectiveness including clinical samples 表1. 嗅觉训练影响抑郁症状的研究总结
CF:Citrus fragrance group柑橘芳香组;AD:Antidcpressants group抗抑郁药组;OT:Olfactory training group嗅觉训练组;SOTR:Standard olfactory training regimen (two training sessions per day)标准嗅觉训练方案(每天两次训练);IOTR:Intense olfactory training regimen (two training sessions per day)强化嗅觉训练方案(每天四次训练)。
但也有一些研究表明,嗅觉训练对抑郁症状改善的作用有限(
表1
)。
Pabel et al. (2020)
的研究对102名抑郁症患者采用随机对照临床试验,实验组(n = 53)接受每天两次、时长16周的嗅觉训练,控制组(n = 49)进行同等时长的数独训练,结果发现两组的抑郁症状均有缓解,但并未发现嗅觉训练组相比控制组有更显著的效果。对于这种结果,作者给出了两种解释:1) 研究中有超过一半的所有参与者在训练之前退出了干预,因此这种原因可能是由于重度抑郁患者难以坚持完整的嗅觉训练方案而造成的;2) 研究的被试均来自于门诊,他们的嗅觉能力都在健康水平之内,这可能导致嗅觉训练难以进一步改善嗅觉功能和抑郁症状。这项研究结果给了我们一定的启示,即嗅觉训练可能只对有明显嗅觉障碍的抑郁患者有效。另一项研究使用葡萄柚、熏衣草、柠檬草、依兰和薄荷五种气味对55名被试进行嗅觉训练,每日两次或四次,训练持续108到340天。结果表明,两种训练频率均显著提高了被试的嗅觉功能和言语流畅性,尤其是在嗅觉基线较低的参与者中。然而,对于抑郁症状和正向情绪没有明显影响,可能是因为研究中的被试未表现出抑郁症状,因此结果可能受到天花板效应的影响(
Oleszkiewicz et al., 2022
)。
嗅觉系统与大脑的情绪系统密切相关,嗅觉训练对抑郁症状的改善可能归功于其对相关脑区的影响。
Negoias et al. (2010)
发现急性重性抑郁症患者表现出显著较低的嗅觉灵敏度和较小的嗅球体积。嗅觉训练可以刺激嗅觉神经元的再生和嗅球的重塑,从而改善嗅觉功能。研究表明,特发性嗅觉丧失患者(
Mahmut et al., 2020
)和健康成人(
Negoias et al., 2017
)在嗅觉训练后嗅球灰质体积增加。在健康受试者中,嗅觉训练增加了右额下回和右内嗅皮质等高级嗅觉功能脑区的皮质厚度(
Al Ain et al., 2019
;
Han et al., 2021
)。此外,嗅觉训练还会引起功能性神经解剖连接的改变。研究发现,接受嗅觉训练的嗅觉障碍患者在大脑的多个区域和功能网络中发生了变化,这些变化不仅限于嗅觉处理区域,还包括其他与感觉和认知相关的区域。
Kollndorfer et al. (2014)
发现,嗅觉障碍患者经过嗅觉训练后,表现出嗅觉、躯体感觉和整合性网络中的信号强度增强和功能连接数量增加。在创伤后嗅觉丧失的患者中,嗅觉训练导致了额叶皮层的自抑制连接增强,从扣带皮层到脑岛的兴奋性连接增强,这些区域与情绪调节、决策和内在状态的感知有关,说明嗅觉训练提高了这些患者的大脑自我调节(
Hosseini et al., 2020
)。
Pellegrino et al. (2019)
的研究发现,经过嗅觉训练的患者在右上额叶回和语义处理区域的激活增加,这表明可能促进高级认知功能的恢复,如记忆、语言处理和情绪调节。这些发现说明,嗅觉训练不仅可以帮助患者恢复嗅觉功能,还可能通过增强大脑的功能性连接和调整感官系统的失衡来改善患者的整体认知和情绪健康。一些动物实验表明,嗅觉训练对嗅觉神经系统的影响可能是由于气味对嗅觉感受器、神经元和突触等方面的影响。在啮齿动物研究中,发现3周的嗅觉训练可以增加某些嗅觉受体基因(如Olfr1507)的表达。这表明嗅觉训练可能通过上调嗅觉感受器的表达来增强嗅觉灵敏度(
Kim et al., 2020
)。
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