Subjects: Psychology >> Social Psychology submitted time 2023-03-27 Cooperative journals: 《心理学报》
Abstract： Severe stress is one of the major external triggers of emotion-related mental disorders such as post-traumatic stress disorder (PTSD). Stress-induced sustained hyperarousal state is not only a core symptom but also a contributor to other symptoms such as sleep disturbance and negative mood. Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter that regulates emotional response. In addition, the 5-HT system is the target for pharmacological treatment such as selective-serotonin re-uptake inhibitors (SSRIs) for major depressive disorder, PTSD, and other emotional disorders. However, it remains unknown whether serotonin is involved in the hyperarousal state caused by severe stress, as well as the mechanism by which genetic polymorphism in serotonin regulation contributes to the vulnerability of stress-related psychiatric disorders. Tryptophan-hydroxylase-2 (Tph2) is a serotonin synthesizing enzyme that converts tryptophan to 5-hydroxytryptophan in the brain. A genetic deficiency in the expression of Tph2 may lead to a lower level of serotonin in the brain. The present study focused on the role of serotonin in the development of stress-induced hyperarousal, investigating the behavioral effect of Tph2 gene-deficiency after severe stress in a mice model. Mice lacking Tph2 (Tph2-/-) in the brain have a vitally low level of serotonin and a bad health condition, so we used heterozygous Tph2-deficient mice (Tph2+/-) which have been shown to have a mild low level of serotonin in the brain. We measured the auditory startle reflex as an indicator of arousal level at different time points after predator-exposure stress or footshock stress in both male and female Tph2+/- and wild-type mice. The predator-exposure stress was to exposure a mouse to a cat for 5 minutes with a trained experimenter protecting the mouse from direct attack from the cat. The footshock stress was to exposure a mouse to a series of footshock (1.5 mA × 5s × 5, inter-shock interval 60 ~ 120 s) in a shock chamber. Then we measured the auditory startle reflex at 1-, 2-, 10-, and 18-day post-stress. For each startle test session, a total of 30 white noise stimuli were presented to the mice in a sound-isolated chamber (90 dB, 100 dB, 110 dB, ten stimuli for each level). The results showed that the Tph2+/- male mice had a higher level of startle than the non-stressed group at 1, 2, and 10 days after footshock stress, indicating a sustained hyperarousal. However, wild-type male mice only had an increased startle response on the day after the footshock stress. For mice with predator exposure stress, both Tph2+/- male mice and wild-type male mice showed an increased startle response on the first day after the predator stress, but then returned to the same level as the non-stressed mice. We also observed a sex difference in mice’s startle response that the female mice had a lower level of startle amplitude than that of male mice at baseline test before stress. In addition, female mice with different genotypes showed minor differences in their startle response at different time points after both types of stress. The results of the study indicate that the Tph2 genotype interacts with stress types in the regulation of long-term hyperarousal after severe stress events. Our results also provide preclinical evidence that individuals with Tph2 gene deficiency may be more vulnerable to stress-induced hyperarousal and highlight the potential of targeting the serotonin system for post-traumatic intervention.
Subjects: Psychology >> Physiological Psychology submitted time 2021-12-20
Abstract： Severe stress is one of the major external triggers of emotion-related mental disorders such as post-traumatic stress disorder (PTSD). Stress-induced sustained hyperarousal state is not only a core symptom but also a contributor to other symptoms such as sleep disturbance and negative mood. Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter that regulates emotional response. In addition, the 5-HT system is the target for pharmacological treatment such as selective-serotonin re-uptake inhibitors (SSRIs) for major depressive disorder, PTSD, and other emotional disorders. However, it remains unknown whether serotonin is involved in the hyperarousal state caused by severe stress, as well as the mechanism by which genetic polymorphism in serotonin regulation contributes to the vulnerability of stress-related psychiatric disorders. Tryptophan-hydroxylase-2 (Tph2) is a serotonin synthesizing enzyme that converts tryptophan to 5-hydroxytryptophan in the brain. A genetic deficiency in the expression of Tph2 may lead to a lower level of serotonin in the brain. The present study focused on the role of serotonin in the development of stress-induced hyperarousal, investigating the behavioral effect of Tph2 gene-deficiency after severe stress in a mice model. Mice lacking Tph2 (Tph2-/-) in the brain have a vitally low level of serotonin and a bad health condition, so we used heterozygous Tph2-deficient mice (Tph2+/-) which have been shown to have a mild low level of serotonin in the brain. We measured the auditory startle reflex as an indicator of arousal level at different time points after predator-exposure stress or footshock stress in both male and female Tph2+/- and wild-type mice. The predator-exposure stress was to exposure a mouse to a cat for 5 minutes with a trained experimenter protecting the mouse from direct attack from the cat. The footshock stress was to exposure a mouse to a series of footshock (1.5 mA × 5s × 5, inter-shock interval 60 ~ 120 s) in a shock chamber. Then we measured the auditory startle reflex at 1-, 2-, 10-, and 18-day post-stress. For each startle test session, a total of 30 white noise stimuli were presented to the mice in a sound-isolated chamber (90 dB, 100 dB, 110 dB, ten stimuli for each level). The results showed that the Tph2+/- male mice had a higher level of startle than the non-stressed group at 1, 2, and 10 days after footshock stress, indicating a sustained hyperarousal. However, wild-type male mice only had an increased startle response on the day after the footshock stress. For mice with predator exposure stress, both Tph2+/- male mice and wild-type male mice showed an increased startle response on the first day after the predator stress, but then returned to the same level as the non-stressed mice. We also observed a sex difference in mice’s startle response that the female mice had a lower level of startle amplitude than that of male mice at baseline test before stress. In addition, female mice with different genotypes showed minor differences in their startle response at different time points after both types of stress. The results of the study indicate that the Tph2 genotype interacts with stress types in the regulation of long-term hyperarousal after severe stress events. Our results also provide preclinical evidence that individuals with Tph2 gene deficiency may be more vulnerable to stress-induced hyperarousal and highlight the potential of targeting the serotonin system for post-traumatic intervention.
Peer Review Status:
Awaiting Review
Subjects: Psychology >> Cognitive Psychology submitted time 2018-09-07 Cooperative journals: 《心理学报》
Abstract： 决策是每个人每天都会进行的活动。二择一时, 有人择一而终, 有人变换不定。这种个体差异可能与坚持性人格和认知灵活性有关。本研究旨在探讨这种行为特征背后的认知神经机制, 以便进一步理解决策变换中存在的个体差异。本研究采用了单变量和多变量体素形态学分析的方法分析了350名大学生(其中女性194人, 平均年龄19.97岁)在随机猜牌任务中的换牌频率与大脑灰质体积的相关情况, 探讨了坚持性人格特质和认知灵活性与换牌频率的关系, 并考察了两者在大脑灰质体积与换牌频率中的中介作用。单变量和多变量体素形态学分析结果都表明, 左侧后扣带回、右侧额中回、右侧额极和右侧脑岛区域的灰质体积可以预测被试的换牌频率; 坚持性人格和认知灵活性在其中起到了中介作用。这些结果阐释了换牌频率个体差异的认知机制和神经基础, 对理解为何有的人一味坚持, 而有的人灵活变换背后的原因提供了理论基础, 同时为开发改善非理性决策行为的方法提供了重要的参考价值。
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