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Abstract：
The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment, it is unclear whether efficacy may be influenced by dose frequency or genotype.
In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex.
A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype.
Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.
In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex.
A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype.
Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.
摘要：
神经肽催产素被认为是通过调节杏仁核介导的社会情绪行为来治疗社会功能障碍的有希望的疗法。虽然临床试验报告了慢性治疗的一些好处，目前尚不清楚疗效是否受剂量频率或基因型的影响.
在一个随机的，双盲,安慰剂对照药物功能磁共振成像试验（150名男性受试者），我们调查了急性和不同慢性(每天或隔日,共5天)鼻内催产素(24个国际单位)对杏仁核对面部情绪的反应的影响和催产素受体基因型介导的治疗敏感性.我们还研究了杏仁核和前额叶皮层之间静息状态功能连接的类似影响。
单剂量的催产素减少杏仁核对所有面部情绪的反应，但对于威胁（恐惧和愤怒）和快乐的面孔，这种效应在每日给药5天后消失,但通过隔日给药维持.后一种剂量方案还增强了恐惧面孔的相关焦虑-唤醒衰减。催产素对减少杏仁核对面部情绪的反应的作用仅发生在rs53576的AA纯合子和rs2254298的A携带者中。催产素对静息状态功能连接的影响不受剂量频率或受体基因型的影响。
罕见的慢性催产素给药可能在治疗上最有效，其抗焦虑神经和行为作用在男性中是高度基因型依赖性的。
在一个随机的，双盲,安慰剂对照药物功能磁共振成像试验（150名男性受试者），我们调查了急性和不同慢性(每天或隔日,共5天)鼻内催产素(24个国际单位)对杏仁核对面部情绪的反应的影响和催产素受体基因型介导的治疗敏感性.我们还研究了杏仁核和前额叶皮层之间静息状态功能连接的类似影响。
单剂量的催产素减少杏仁核对所有面部情绪的反应，但对于威胁（恐惧和愤怒）和快乐的面孔，这种效应在每日给药5天后消失,但通过隔日给药维持.后一种剂量方案还增强了恐惧面孔的相关焦虑-唤醒衰减。催产素对减少杏仁核对面部情绪的反应的作用仅发生在rs53576的AA纯合子和rs2254298的A携带者中。催产素对静息状态功能连接的影响不受剂量频率或受体基因型的影响。
罕见的慢性催产素给药可能在治疗上最有效，其抗焦虑神经和行为作用在男性中是高度基因型依赖性的。
