Post R M, Kimbrell T A, McCann U, Dunn R T, George M S, Weiss S R
NIMH, Bethesda MD 20892-1272, USA.
Encephale. 1997 Jun;23 Spec No 3:27-35.
Sismotherapy (ST) brings about numerous neurobiological changes, particularly changes in neuromediators and their receptors, second messengers, neuropeptides and neurotropic factors, a number of which are hypothesized to play a role in the pathophysiology or therapeutics of affective disorders (M. Fink). What is not yet known is which of these mechanisms is crucial for the psychotropic and anticonvulsant effects of ST. However, it is clear that the effects of ST tend to be relatively acute, and do not attack the deep-seated abnormalities that are the underlying causes of recurrences of affective disorders. This is corroborated by the fact that in animals, most of the effects of ECS on catecholamines and their receptors (and on receptors for benzodiazepines or neuropeptides such as TRH) tend to be relatively transient, and in most cases have been found to represent compensatory adaptations to the induced motor convulsions. However, recent preclinical data using attenuation, and clinical findings using reiterated transcranial magnetic stimulation (rTMS), suggest that it may not be necessary to provoke a clonic convulsion in order to achieve the beneficial psychotropic and anticonvulsant effects of ST. In rodents receiving stimulation to the cerebellar tonsil, seven daily subacute low-frequency sessions (stimulation at 1 Hz for 15 minutes) produced clear improvement in clonic convulsions and in post-discharge thresholds, together with durable inhibition of convulsions when stimulation was resumed (Weiss et al., 1995). Stimulation at 1 Hz for 15 minutes was more effective than stimulation at 10 or 20 Hz in attenuating convulsions. Although reiterated ECS also induced an anti-triggering effect, this dissipated rapidly over five days (Post et al., 1984). It is of great interest that recent publications have shown that rTMS at 10 or 20 Hz to the left frontal cortex, administered to patients suffering from refractory depression (George et al., 1995) or to patients (hospitalised or not) with milder degrees of depression (Pasquale-Leon et al., 1996), had a moderate or marked antidepressant effect. In these studies, rTMS showed few unwanted effects (other than mild pain in some patients, due to contraction of the temporal muscles); it did not induce motor convulsions, and did not, as such, appear to be associated with the memory loss described in subjective accounts or in preliminary neuropsychological tests (Little and Kimbrell et al., 1996). The optimal frequencies, durations and positions for rTMS to maximise its antidepressant effect still remain to be determined. However, the first controlled and open studies have tended to show that (because of the capacity of rapid magnetic fluxes to produce sub-convulsant electrical discharges that are relatively localised in the brain), rTMS may be found to be a clinically useful antidepressant model. This would suggest the possibility that some of the neurochemical changes induced by the clonic convulsions of ECS could be directly induced by stimulation at the very edge of the threshold (but still below it); this would open up the hope that one day these endogenous neurochemical processes could be identified and exploited in an optimal way for therapeutic purposes.
痉挛疗法(ST)会引发众多神经生物学变化,尤其是神经介质及其受体、第二信使、神经肽和神经营养因子的变化,其中一些被认为在情感障碍的病理生理学或治疗中发挥作用(M. 芬克)。目前尚不清楚这些机制中哪一种对ST的精神otropic作用和抗惊厥作用至关重要。然而,很明显,ST的作用往往相对较为急性,并且不会针对作为情感障碍复发根本原因的深层异常。这一点得到了以下事实的证实:在动物中,电惊厥休克(ECS)对儿茶酚胺及其受体(以及苯二氮䓬或神经肽如促甲状腺激素释放激素的受体)的大多数作用往往相对短暂,并且在大多数情况下已发现这些作用代表对诱导的运动性惊厥的代偿性适应。然而,最近使用衰减的临床前数据以及使用重复经颅磁刺激(rTMS)的临床研究结果表明,为了实现ST有益的精神otropic和抗惊厥作用,可能不必引发阵挛性惊厥。在接受小脑扁桃体刺激的啮齿动物中,每天进行七次亚急性低频刺激(1赫兹刺激15分钟)可使阵挛性惊厥和放电后阈值明显改善,并且在恢复刺激时可持久抑制惊厥(魏斯等人,1995年)。在减轻惊厥方面,1赫兹刺激15分钟比10或20赫兹刺激更有效。尽管重复的ECS也会诱导抗触发作用,但这种作用在五天内迅速消失(波斯特等人,1984年)。非常有趣的是,最近的出版物表明,对难治性抑郁症患者(乔治等人,1995年)或轻度抑郁症患者(住院或未住院)(帕斯夸莱 - 莱昂等人,1996年)的左额叶皮层施加10或20赫兹的rTMS具有中度或显著的抗抑郁作用。在这些研究中,rTMS几乎没有不良影响(除了一些患者因颞肌收缩而出现的轻微疼痛);它不会诱导运动性惊厥,并且本身似乎与主观描述或初步神经心理学测试中所述的记忆丧失无关(利特尔和金布雷尔等人,1996年)。为了使rTMS的抗抑郁作用最大化,其最佳频率、持续时间和位置仍有待确定。然而,首批对照和开放研究倾向于表明,(由于快速磁通量能够产生相对局限于大脑中的亚惊厥性放电),rTMS可能会被发现是一种临床上有用的抗抑郁模型。这将表明,ECS阵挛性惊厥诱导的一些神经化学变化可能可以通过在阈值边缘(但仍低于阈值)的刺激直接诱导;这将带来希望,即有一天这些内源性神经化学过程能够被识别并以最佳方式用于治疗目的。