针对应激激素系统治疗抑郁症和焦虑症的精准精神病学方法--以 V1b-拮抗剂为例。

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacopsychiatry Pub Date : 2024-11-01 Epub Date: 2024-08-19 DOI:10.1055/a-2372-3549
Florian Holsboer, Marcus Ising
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引用次数: 0

摘要

抑郁症药物治疗的未来在于精准医疗方法,即认识到抑郁症是一种由不同病因导致症状的疾病。这种方法要求摒弃当前的诊断类别,因为当前的诊断类别过于宽泛,足以让人们遵循 "一刀切 "的范式,这与常规使用 "广谱 "单胺抗抑郁药是相辅相成的。与肿瘤学类似,通过实施实验室检测来缩小过度包容的诊断窗口,从而指导有针对性的治疗,将是克服当前药物研发危机的重要一步。因此,这一应激激素系统被认为是值得研究的目标。通过拮抗同源的 CRHR1 和 V1b 受体,阻断脑内应激反应神经肽、促肾上腺皮质激素释放激素(CRH)和精氨酸加压素(AVP)的非肽能药物更具针对性。如果患者的抑郁症状是由 V1b 信号过度活跃引起的,那么 V1b 受体拮抗剂应作为一线治疗药物。为了识别 V1b 受体过度活跃的患者,人们开发了一种神经内分泌测试,即所谓的 dex/CRH 测试,它可以显示中枢 AVP 的释放,但由于过于复杂而无法常规使用。因此,我们将这种检测方法转化为一种基于基因的 "近似患者 "检测方法,可以立即确定抑郁症患者的症状是否是由过度活跃的 V1b 受体信号传导引起的。我们相信,这种精准医疗方法将成为抑郁症药物疗法的下一个重大创新。
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Precision Psychiatry Approach to Treat Depression and Anxiety Targeting the Stress Hormone System - V1b-antagonists as a Case in Point.

The future of depression pharmacotherapy lies in a precision medicine approach that recognizes that depression is a disease where different causalities drive symptoms. That approach calls for a departure from current diagnostic categories, which are broad enough to allow adherence to the "one-size-fits-all" paradigm, which is complementary to the routine use of "broad-spectrum" mono-amine antidepressants. Similar to oncology, narrowing the overinclusive diagnostic window by implementing laboratory tests, which guide specifically targeted treatments, will be a major step forward in overcoming the present drug discovery crisis.A substantial subgroup of patients presents with signs and symptoms of hypothalamic-pituitary-adrenocortical (HPA) overactivity. Therefore, this stress hormone system was considered to offer worthwhile targets. Some promising results emerged, but in sum, the results achieved by targeting corticosteroid receptors were mixed.More specific are non-peptidergic drugs that block stress-responsive neuropeptides, corticotropin-releasing hormone (CRH), and arginine vasopressin (AVP) in the brain by antagonizing their cognate CRHR1-and V1b-receptors. If a patient's depressive symptomatology is driven by overactive V1b-signaling then a V1b-receptor antagonist should be first-line treatment. To identify the patient having this V1b-receptor overactivity, a neuroendocrine test, the so-called dex/CRH-test, was developed, which indicates central AVP release but is too complicated to be routinely used. Therefore, this test was transformed into a gene-based "near-patient" test that allows immediate identification if a depressed patient's symptomatology is driven by overactive V1b-receptor signaling. We believe that this precision medicine approach will be the next major innovation in the pharmacotherapy of depression.

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来源期刊
Pharmacopsychiatry
Pharmacopsychiatry 医学-精神病学
CiteScore
7.10
自引率
9.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Covering advances in the fi eld of psychotropic drugs, Pharmaco psychiatry provides psychiatrists, neuroscientists and clinicians with key clinical insights and describes new avenues of research and treatment. The pharmacological and neurobiological bases of psychiatric disorders are discussed by presenting clinical and experimental research.
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