Blum Kenneth, Sharafshah Alireza, Khalsa Jag, Uwe-Lewandrowski Kai, Mohankumar Kavya, Thanos Panayotis K, Pinhasov Albert, Baron David, Dennen Catherine A, Morgan Joseph J, Lindenau Marco, Elman Igor, Gardner Eliot L, Gold Mark S, Modestino Edward J, Brian Fuehrlein, Carney Paul R, Cortese Rene, Bowirrat Abdalla, Madigan Margaret A, Sunder Keerthy, Lorio Morgan P, Zeine Foojan, Jafari Nicole, Makale Milan T, Bagchi Debasis, Ceccanti Mauro, Fiorelli Rossano K A, Schimidt Sérgio Luís, Sipple Daniel, Lewandrowski Alexander P L, Matare Gianni, Mahajan Shaurya, Mahajan Yatharth, Hanna Colin, Gastelu Daniel, Swaroop Anand, Fliegelman Chynna, Badgaiyan Rajendra D
Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, USA.
J Addict Psychiatry. 2025;9(1):8-13. doi: 10.17756/jap.2025-050. Epub 2025 Aug 29.
Addiction neuroscience explores the complex interplay between genetic, neurobiological, environmental, and socio-spiritual factors underlying substance and behavioral addictions. Over the past three decades, research in this domain has identified critical molecular and epigenetic mechanisms-particularly those affecting dopaminergic signaling and reward pathways-that contribute to both vulnerability and resilience to addictive behaviors. Central to this understanding is the concept of reward deficiency syndrome (RDS), first introduced by Kenneth Blum, which posits that hypodopaminergic functioning predisposes individuals to seek maladaptive rewards. Advances in neurogenetics, including the identification of key polymorphisms such as the DRD2 A1 allele, have paved the way for precision tools like the genetic addiction risk severity (GARS) test. This test, alongside pro-dopaminergic nutraceutical interventions like KB220, demonstrates the potential for early detection and individualized treatment of "pre-addiction" risk states. Despite ongoing reliance on opioids for opioid use disorder (OUD), emerging paradigms advocate for dopamine homeostasis through non-addictive, integrative approaches. Furthermore, the integration of whole genome sequencing data can be used for Genome-Wide Association Studies (GWAS), multi-omics, and machine learning into clinical practice holds promise for advancing personalized medicine in addiction treatment. As the field progresses, addressing health equity and improving genomic representation across populations remain critical goals. This evolving framework underscores the importance of leveraging genomic insights to prevent, predict, and personalize interventions for addiction and mental illness at scale.
成瘾神经科学探索了物质成瘾和行为成瘾背后的遗传、神经生物学、环境及社会精神因素之间的复杂相互作用。在过去三十年中,该领域的研究已经确定了关键的分子和表观遗传机制,尤其是那些影响多巴胺能信号传导和奖赏通路的机制,这些机制导致了成瘾行为的易感性和恢复力。理解这一点的核心是奖赏缺乏综合征(RDS)的概念,该概念由肯尼斯·布卢姆首次提出,它假定多巴胺功能低下会使个体倾向于寻求适应不良的奖赏。神经遗传学的进展,包括鉴定关键的基因多态性,如DRD2 A1等位基因,为诸如遗传成瘾风险严重程度(GARS)测试等精准工具铺平了道路。这项测试,连同像KB220这样的促多巴胺能营养干预措施,证明了早期检测和个体化治疗“成瘾前”风险状态的潜力。尽管目前仍依赖阿片类药物治疗阿片类药物使用障碍(OUD),但新出现的范式主张通过非成瘾性的综合方法实现多巴胺稳态。此外,将全基因组测序数据整合用于全基因组关联研究(GWAS)、多组学和机器学习,并将其纳入临床实践,有望推动成瘾治疗的个性化医疗。随着该领域的发展,解决健康公平问题和改善不同人群的基因组代表性仍然是关键目标。这个不断发展的框架强调了利用基因组见解大规模预防、预测和个性化成瘾及精神疾病干预措施的重要性。