Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, University of Zurich, Zürich, Switzerland.
Neuroscience Center Zurich, University of Zurich and the ETH Zurich, Zürich, Switzerland.
Transl Psychiatry. 2020 Sep 18;10(1):315. doi: 10.1038/s41398-020-00999-9.
Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD. The Wnt-signaling pathway is known to orchestrate cellular proliferation, polarity, and differentiation, and the mTOR pathway is involved in several significant processes of neurodevelopment and synaptic plasticity. As a result, dysregulations of these pathways in a time-dependent manner could lead to neurodevelopmental delays, resulting in ADHD phenotype. This review presents further evidence supporting our hypothesis by combining results from studies on ADHD and Wnt- or mTOR-signaling and the influence of genetics, methylphenidate treatment, Omega-3 supplementation, and stress.
注意缺陷多动障碍（ADHD）是儿童和青少年中最常见的精神神经发育障碍之一。尽管 ADHD 已经研究了近一个世纪，但 ADHD 的病因和发病机制在很大程度上仍不清楚。然而，先前研究的结果形成了一个新的假设：除了众所周知的 ADHD 多因素病因外，最近的证据表明，遗传和环境因素之间的相互作用，特别是 Wnt 和 mTOR 信号通路，可能在 ADHD 的发病机制中起重要作用。Wnt 信号通路已知可协调细胞增殖、极性和分化，mTOR 通路参与神经发育和突触可塑性的几个重要过程。因此，这些途径在时间依赖性方面的失调可能导致神经发育延迟，导致 ADHD 表型。通过结合 ADHD 与 Wnt 或 mTOR 信号以及遗传、哌醋甲酯治疗、ω-3 补充剂和应激影响的研究结果，本综述提供了进一步支持我们假设的证据。
