The role of serotonin in emotional processing

血清素在情绪处理中的作用

• 批准号: 7969424
• 负责人: james r blair
• 金额: $ 48.49万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7969424
• 关键词: Acute; Affect; Affective; Alleles; Amygdaloid structure; Anxiety; Anxiety Disorders; Attention; Behavior; Behavioral; Cues; Data; Decision Making; Development; Diagnostic; Disease; Emotional; Emotional disorder; Emotions; Face; Feedback; Fright; Functional disorder; Generalized Anxiety Disorder; Genes; Genetic Polymorphism; Genotype; Goals; Homozygote; Human; Impairment; Individual; Major Depressive Disorder; Measures; Moods; Neurocognitive; Neurotransmitters; Operant Conditioning; Pathway interactions; Performance; Placebos; Play; Post-Traumatic Stress Disorders; Process; Psychological reinforcement; Punishment; Reversal Learning; Rewards; Role; Series; Serotonin; Stimulus; System; Tryptophan; Work; base; cognitive neuroscience; genetic analysis; improved; insight; interest; neuroimaging; patient population; relating to nervous system; response; reward processing; serotonin transporter; showing emotion; social; transmission process

Our work thus far has investigated the effects of altering serotonergic systems in humans using acute tryptophan depletion on behavioral performance during emotional processing tasks. Additionally, we have begun to determine how acute tryptophan depletions effects on emotional processing vary as a function of serotonin transporter genotype. Evidence suggests that manipulating serotonin using pharmacological challenges impacts different domains of emotional processing, and the effect of pharmacological challenges on emotional processing varies as a function of serotonin-related genotype (e.g., polymorphisms in the serotonin transporter). We found that both genotype and acute tryptophan depletion modulated dissociable components of emotional processing. Furthermore we found that the effects of altering serotonin transmission via tryptophan depletion were often genotype-dependent. For example, although tryptophan depletion in and of itself did not disrupt fear expression recognition, it did impair fear recognition in individuals who carried the short allele of the serotonin transporter gene. This indicates that genotype or changes in serotonergic transmission alone may not necessarily be sufficient to affect processing of social cues, but genotype may influence this domain of emotional processing when faced with a pharmacological challenge or when serotonin systems are altered. Another form of emotional processing that is important in the context of mood and anxiety disorders is reinforcement processing. Processing reward and punishment directly guides behaviors and decision making, and atypical reinforcement processing occurs in a variety of psychiatric conditions. When we began our studies, there was evidence suggesting that altering serotonin systems reduces responsivity to reward and increases sensitivity to punishment. Thus, we attempted to investigate these claims further to determine the role of serotonin in reinforcement processing. In a series of studies, we found that altering serotonin systems via acute tryptophan depletion altered reinforcement processing, and that this effect was, in some cases, genotype dependent. In one study, using an instrumental learning task, we found that tryptophan depletion impaired reward processing. Interestingly, individuals who were homozygous for the long version of the serotonin transporter gene responded differently to punishment than did carriers of the short version. Long homozygotes were slower to avoid the bad (punishment) stimuli than were short carriers. We also looked at the effects of tryptophan depletion on response reversal, which measures the ability to change ones response when a previously rewarded behavior becomes a punished behavior. We found that tryptophan-depleted long carriers were not as efficient at using negative feedback to guide appropriate responding compared to tryptophan-depleted short carriers. Long carriers were also less likely to maintain correct responding in the face of probabilistic punishment during tryptophan depletion than tryptophan-depleted s carriers and long carriers who received the placebo. To further explore the role of serotonin in sensitivity to reward and punishment, we investigated the effects of tryptophan depletion on a decision making task, which requires individuals to choose between two objects associated with different amounts of reward or punishment. We found that ATD altered sensitivity to punishment-related information and that sensitivity to punishment varied as a function of transporter genotype. Over the past 12 months, we have extended our previous work by examining the selective effects of tryptophan depletion on neural regions engaged in expression processing, emotional attention and reversal learning. While the data from the emotional attention and reversal learning paradigms is currently being processed, we have observed the effects of tryptophan depletion on reducing amygdala responsiveness (and the responsiveness of associated regions) to emotional expressions.

到目前为止，我们的工作已经研究了在情绪处理任务期间，使用急性色氨酸耗竭改变人类的色氨酸能系统对行为表现的影响。 此外，我们已经开始确定急性色氨酸耗竭对情绪处理的影响如何作为5-羟色胺转运蛋白基因型的函数而变化。 有证据表明，使用药理学挑战来操纵5-羟色胺会影响情绪处理的不同领域，并且药理学挑战对情绪处理的影响随5-羟色胺相关基因型的变化而变化（例如，5-羟色胺转运蛋白的多态性）。 我们发现，基因型和急性色氨酸耗竭调制的情绪处理的可分离成分。 此外，我们发现，通过色氨酸耗竭改变5-羟色胺传输的影响往往是基因型依赖性的。 例如，虽然色氨酸缺失本身并不会破坏恐惧表达识别，但它确实会损害携带5-羟色胺转运蛋白基因短等位基因的个体的恐惧识别。 这表明，基因型或单独的多巴胺能传递的变化可能不一定足以影响社会线索的处理，但基因型可能会影响这一领域的情绪处理时，面临着药理学的挑战，或当血清素系统被改变。 在情绪和焦虑障碍的背景下，另一种重要的情绪处理形式是强化处理。 奖励和惩罚的加工直接指导行为和决策，非典型强化加工发生在各种精神疾病中。 当我们开始研究时，有证据表明，改变血清素系统会降低对奖励的反应性，增加对惩罚的敏感性。 因此，我们试图进一步研究这些说法，以确定5-羟色胺在强化过程中的作用。 在一系列研究中，我们发现，通过急性色氨酸耗竭改变血清素系统会改变强化过程，而且这种影响在某些情况下是基因型依赖的。 在一项研究中，使用工具性学习任务，我们发现色氨酸耗尽损害了奖励处理。 有趣的是，携带长型5-羟色胺转运体基因的个体对惩罚的反应与携带短型5-羟色胺转运体基因的个体不同。 长的纯合子比短的携带者更慢，以避免坏（惩罚）的刺激。 我们还研究了色氨酸耗尽对反应逆转的影响，反应逆转测量了当先前奖励的行为变成惩罚的行为时改变反应的能力。 我们发现，与耗尽的短载体相比，耗尽的长载体在使用负反馈来指导适当的反应方面没有那么有效。 长期携带者也不太可能保持正确的反应，在面对概率的惩罚，在色氨酸耗尽比色氨酸耗尽的s运营商和长期运营商谁收到安慰剂。 为了进一步探索血清素在对奖励和惩罚的敏感性中的作用，我们研究了色氨酸耗尽对决策任务的影响，该任务要求个体在与不同奖励或惩罚量相关的两个对象之间进行选择。 我们发现ATD改变了对惩罚相关信息的敏感性，并且对惩罚的敏感性随转运蛋白基因型的变化而变化。 在过去的12个月里，我们通过研究色氨酸缺失对参与表达处理，情绪注意和逆转学习的神经区域的选择性影响，扩展了我们以前的工作。 虽然来自情绪注意和逆转学习范式的数据目前正在处理中，但我们已经观察到色氨酸耗尽对降低杏仁核对情绪表达的反应性（以及相关区域的反应性）的影响。