人类行为的遗传学

D. Streid, Katherine J. Kim
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引用次数: 0

摘要

行为障碍是由环境、生活方式和遗传因素引起的。过去的研究已经显示了一些主要的行为神经精神疾病的遗传证据,如精神分裂症、抑郁症和双相情感障碍。在这些情况下,某些遗传缺陷从父母几代遗传下来,增加了后代遗传某种特定疾病的风险。虽然神经精神疾病的易感性不能仅仅归因于遗传,但研究一个人的基因构成如何影响人类行为的各个方面是很重要的。揭示基因和行为之间的这种联系可能会导致发现涉及高度普遍的神经反应和疾病发展的新的生物学因素。最近的一项行为遗传学研究表明,非理性恐惧症可能有遗传基础。它强调了一种可能性,即恐惧症是一种通过家族基因传递下来的遗传防御机制。在这项研究中,来自埃默里医学院的研究人员迪亚斯和雷斯勒在对老鼠进行电击之前,通过将老鼠暴露在闻起来像樱花的化学苯乙酮的气味中,让它们进行恐惧调节。这些小鼠的后代(不像他们的父母那样暴露在相同的条件下)对苯乙酮的气味表现出恐惧的反应,即使是第一次闻到它。这表明它们对化学气味有一种恐惧症。在后代小鼠的嗅球中也发现了结构异常。在对小鼠精子DNA进行测序后,迪亚斯发现编码M71的基因(一种被苯乙酮激活的odo受体)在条件条件下的亲代和直系后代中被甲基化。然而,尚不清楚精子DNA的这种表观遗传改变是否导致了后代气味敏感性的提高。有可能是不同的生物机制共同作用,将遗传的祖先经历转化为后代的非理性恐惧症。行为遗传学的其他研究表明,一些神经精神疾病的遗传性较弱,或者遗传成分较弱。例如,虽然基因可能占某些神经精神疾病(如精神分裂症或双相情感障碍)风险的一半以上,但焦虑和抑郁的可遗传性似乎较低。冷泉港实验室(Cold Spring Harbor Laboratory)的Pine博士表示,大约30-50%的焦虑和抑郁风险是遗传的,而另外50% - 70%的风险可能归因于环境因素,如药物使用、压力、饮食和童年经历。焦虑症是美国最常见的精神疾病,影响了总人口的18%。抑郁症也很常见,大约10%的美国人在他们生命中的某个阶段经历过严重的抑郁症。尽管患病率很高,但与其他神经精神疾病相比,焦虑和抑郁的遗传倾向较弱。作为科学家,我们必须确定为什么会这样。是因为基因缺陷数量的不同吗?例如,与焦虑和抑郁相关的基因变异是否少于与其他更易遗传的疾病相关的基因变异?或者是抑郁/焦虑基因在进化上不那么保守?只有回答了这些问题,我们才能对这些疾病的遗传根源有一个坚定的了解,并找到预防或对抗这些疾病的方法。我们必须检查基因缺陷本身。也许,在遗传率相对较低的行为障碍中,基因变异只对大脑的主要通路造成最小程度的破坏。在这种情况下,研究引发行为反应的非遗传因素将是明智的。此外,心理动力学治疗方法——在精神病医生的帮助下减轻病人的精神紧张——可能比侵入性的医疗程序更有帮助。另一方面,个性化医疗,如基因治疗,可能是治疗精神分裂症等显著遗传性疾病的最佳选择。通过基因检测的进步,医生能够进行症状前诊断测试,以了解有遗传性神经系统疾病家族史的患者的风险。检测可以检测异常,包括患者DNA或RNA样本中缺失或严重改变的基因部分,或失活或丢失的基因。在其他情况下,测试可能会检测到来自单个基因的过量RNA,表明它在体内过度表达。识别和修复遗传密码中这些有问题的序列需要广泛的人类基因组知识。提供个性化医疗的医生必须考虑到病人的基因构成,以确定针对某种疾病的最佳治疗形式。 通过基因研究,我们正在慢慢揭开许多神经精神疾病的生物学基础。了解基因在高度普遍的神经反应(如焦虑和恐惧症)中的作用,对于为患有这些疾病的患者设计有效的治疗方法至关重要。具体来说,通过识别与遗传性神经精神疾病相关的遗传标记,我们可以分析患者的疾病遗传风险和对现有药物治疗的反应性。这些知识将对医学界和医学的未来产生强大的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Genetics of Human Behavior
Behavioral disorders arise from environmental, lifestyle, and genetic factors. Past studies have shown evidence for the hereditability of several major behavioral neuropsychiatric disorders, such as schizophrenia, depression, and bipolar disorder. In these cases, certain genetic defects are passed down from parental generations and increase an offspring’s risk of inheriting a specific disorder. While neuropsychiatric disease susceptibility cannot be attributed solely to genetics, it is important to study how one’s genetic makeup can affect various facets of human behavior. Uncovering this link between genes and behavior could lead to the discovery of new biological factors involved in the development of highly prevalent neurological responses and disorders. A recent study in behavioral genetics has shown that there may be a genetic basis for irrational phobias. It highlights the possibility that phobias are a form of inherited defense mechanism passed down through familial genes. In this study, researchers Dias and Ressler from the Emory School of Medicine subjected mice to fear conditioning by exposing them to the scent of chemical acetophenone, which smells like cherry blossoms, before administering electric shocks to the mice. Offspring of these mice (which were not exposed to the same conditioning as their parents) showed fearful responses to the odor of acetophenone, even when smelling it for the first time. This demonstrated that they had acquired a phobia of the chemical odor. Structural abnormalities were also discovered in the olfactory bulbs of the offspring mice. Upon sequencing the mice’s sperm DNA, Dias found that the gene encoding M71, an odo receptor activated by acetophenone, was methylated in the conditioned parental and direct offspring generations. However, it is unknown whether this epigenetic alteration in sperm DNA was responsible for the offspring’s heightened odor sensitivity. It is possible that different biological mechanisms worked in conjunction to translate the inherited ancestral experiences to irrational phobias in the offspring. Other studies in behavioral genetics have shown that some neuropsychiatric disorders are less heritable—or have a weaker genetic component—than others. For example, while genes may account for more than half of the risk for certain neuropsychiatric disorders, such as schizophrenia or bipolar disorder, the hereditability of anxiety and depression appear to be lower. According to Dr. Pine at the Cold Spring Harbor Laboratory, approximately 30-50% of the risk for anxiety and depression is genetic, while the other 50% to 70% of the risk may be attributed to environmental factors, such as substance use, stress, diet, and childhood experiences. Anxiety disorders are the most common form of mental illness in the U.S., affecting 18% of the total population. Depression is also common, with around 10% of Americans experiencing a major depressive disorder at some point in their lives. Despite the high prevalence, genetic disposition for anxiety and depression is weak when compared to other neuropsychiatric disorders. As scientists, we must determine why this is the case. Is it due to a difference in the number of gene defects? For example, are there less genetic variations linked to anxiety and depression than to other more heritable diseases? Or are depression/anxiety genes less evolutionally conserved? Only by answering these questions can we get a firm understanding of the genetic root of these conditions and develop ways to prevent or fight the disorders. We must examine the gene defects themselves. Perhaps, in behavioral disorders with relatively low heritability, the gene variations only minimally disrupt the major pathways of the brain. In such cases, it would be wise to study non-genetic factors that trigger the behavioral response. In addition, a psychodynamic treatment approach – alleviating a patient’s mental tension with the help of a psychiatrist—may be more helpful than invasive medical procedures. On the other hand, personalized medicine, such as gene therapy, may be the best option for treating significantly inheritable disorders, like schizophrenia. Through advancements in gene testing, doctors are able to conduct pre-symptomatic diagnostic tests to see the risk for patients with a family history of inherited neurological disorders. Tests can detect abnormalities, which may include missing or heavily altered sections of a gene, or genes that are inactive or lost, in DNA or RNA samples of patients. In other cases, a test may detect excessive RNA from a single gene, indicating that it is overexpressed in the body. Identifying and fixing these problematic sequences in the genetic code requires extensive knowledge of the human genome. Physicians providing personalized medicine must take into account a patient’s genetic makeup to determine the best form of targeted treatment for an illness. Through genetic research, we are slowly beginning to unravel the biological basis for many neuropsychiatric disorders. Understanding the role of genes in highly prevalent neurological responses, like anxiety and phobias, is crucial for designing effective treatments tailored to patients who are suffering these conditions. Specifically, by identifying the genetic markers associated with inheritable neuropsychiatric diseases, we can analyze a patient’s risk of disease inheritance and responsiveness to existing medical treatment. This knowledge will make a powerful impact on the medical community and the future of medicine.
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