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首页> 外文期刊>The journal of clinical psychiatry >The neurobiology of depression: inroads to treatment and new drug discovery.
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The neurobiology of depression: inroads to treatment and new drug discovery.

机译：抑郁症的神经生物学：介入治疗和新药开发。

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The underlying causes of most mood and anxiety disorders remain unknown. There is a strong heritable component to psychiatric illnesses that, when coupled with environmental influences, results in increased vulnerability. Intensive research efforts have been expended to better characterize the genetic underpinnings of mental illness. However, most psychiatric disorders, including mood and anxiety disorders, are polygenetic in nature rather than determined by traditional autosomal-dominant Mendelian genetics. Recent technological advances, including the completion of the human genome inventory, chromosome mapping, high throughput DNA sequencing, and others, offer the promise of someday identifying the genetic basis of mental illnesses. In parallel, tremendous inroads have been made into understanding the neurobiological basis of mood and anxiety disorders and the influence of life events on risk and resilience. Evidence from preclinical, epidemiologic, and clinical studies has converged to convincingly demonstrate that stressful or traumatic events occurring in early life significantly increase the risk for depression and other psychiatric illnesses in adulthood. Neural circuits containing corticotropin-releasing factor (CRF) have been identified as an important mediator of the stress response. Early-life adversity, such as physical or sexual abuse during childhood, results in long-lasting changes in the CRF-mediated stress response and a greatly increased risk of depression in genetically predisposed persons. Identification and cloning of CRF receptors and characterization of their role in the stress response have enabled a better understanding of maladaptive responses to early-life adversity. In addition, studies of the CRF system have suggested molecular targets for new drug development, biological risk factors, and predictors of treatment response.
机译：大多数情绪和焦虑症的根本原因仍然未知。精神疾病有很强的可遗传性，当与环境因素相结合时，会增加脆弱性。为了更好地描述精神疾病的遗传基础，已经进行了深入的研究。但是，大多数精神疾病，包括情绪和焦虑症，本质上都是多基因的，而不是由传统的常染色体显性孟德尔遗传学确定的。最近的技术进步，包括完成人类基因组清单，染色体定位，高通量DNA测序等，为有朝一日确定精神疾病的遗传基础提供了希望。同时，在了解情绪和焦虑症的神经生物学基础以及生活事件对风险和适应力的影响方面取得了巨大进展。临床前，流行病学和临床研究的证据已经令人信服地证明，在生命早期发生的压力或创伤事件显着增加了成年后抑郁和其他精神疾病的风险。含有促肾上腺皮质激素释放因子（CRF）的神经回路已被确定为应激反应的重要介体。早期的逆境，例如儿童时期的身体或性虐待，会导致CRF介导的应激反应发生长期变化，并大大增加遗传易感者的抑郁风险。 CRF受体的鉴定和克隆以及它们在应激反应中的作用特性已使人们对早期逆境的适应不良反应有了更好的了解。此外，对CRF系统的研究还提出了新药开发的分子靶标，生物学危险因素和治疗反应的预测因子。

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