The role of serotonin in emotional processing

血清素在情绪处理中的作用

基本信息

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
项目类别：
财政年份：
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

项目摘要

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.

迄今为止，我们的工作调查了使用急性色氨酸耗竭对情绪处理任务中行为表现改变人类中血清素能系统的影响。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随着5-羟色胺转运蛋白基因型的变化而变化。有证据表明，使用药理学挑战操纵5-羟色胺会影响情绪处理的不同领域，而药理学挑战对情绪加工的影响随着5-羟色胺相关基因型的函数而变化（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节了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-羟色胺传递的影响通常依赖于基因型。例如，尽管色氨酸耗尽本身并没有破坏恐惧表达识别，但它确实损害了携带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使用血清素能传播的变化不一定足以影响社会提示的处理，但是当面对药理学挑战或更改5-羟色胺系统时，基因型可能会影响该情绪处理的这个领域。情绪处理的另一种形式在情绪和焦虑症的背景下很重要。处理奖励和惩罚直接指导行为和决策，以及非典型的加强处理发生在各种精神科条件下。当我们开始研究时，有证据表明改变5-羟色胺系统会降低对奖励的反应性，并提高对惩罚的敏感性。因此，我们试图进一步研究这些主张，以确定5-羟色胺在增强加工中的作用。在一系列研究中，我们发现通过急性色氨酸耗竭改变了5-羟色胺系统会改变增强处理，在某些情况下，这种作用依赖于基因型。在一项研究中，使用器乐学习任务，我们发现色氨酸耗竭受损奖励处理。有趣的是，对于长妇女转运蛋白基因的长期纯合子的个人对惩罚的反应与短版的载体不同。与短携带者相比，长长的纯合子速度要慢，以避免刺激不良（惩罚）。我们还研究了色氨酸耗竭对响应逆转的影响，该响应逆转衡量了当先前奖励的行为成为一种受惩罚的行为时，它可以衡量改变反应的能力。我们发现，与色氨酸耗尽的短载流子相比，耗尽色氨酸的长载体在使用负反馈方面指导适当的响应效率并不那么有效。长长的载体在色氨酸耗竭期间的概率惩罚中，与耗尽贫困的S携带者和接受安慰剂的长载体相比，在概率惩罚面前保持正确的反应。为了进一步探讨5-羟色胺在对奖励和惩罚的敏感性中的作用，我们研究了色氨酸耗竭对决策任务的影响，这要求个人在与不同量的奖励或惩罚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，对惩罚的敏感性随转运蛋白基因型的函数而变化。在过去的12个月中，我们通过检查色氨酸耗竭对参与表达处理，情感注意力和逆转学习的神经区域的选择性影响来扩展了以前的工作。尽管目前正在处理来自情绪关注和逆转学习范式的数据，但我们观察到色氨酸耗竭对降低杏仁核反应性（以及相关区域的响应性）对情绪表达的影响。