Piekiełko-Witkowska Agnieszka, Duda Monika K, Bogusławska Joanna, Mackiewicz Urszula
Eur Thyroid J. 2025 Jun 11;14(3). doi: 10.1530/ETJ-24-0406. Print 2025 Jun 1.
Autoimmune thyroid disease (AITD) is the most prevalent organ-specific autoimmune condition, encompassing Graves' disease (typically linked with hyperthyroidism) and Hashimoto's thyroiditis (generally associated with hypothyroidism). The growing body of evidence suggests that AITD can interfere with brain function. Here, we review the impact of AITD on cognition, mood, and psychiatric disorders by analysing data from clinical, animal, ex vivo and in vitro studies to reveal the molecular mechanisms by which AITD affects brain function. Most reports indicate a stronger association between cognitive impairments and hyperthyroidism (including AITD-related) than hypothyroidism. Both hypothyroidism and hyperthyroidism are linked with a higher risk of depression. At least some of those effects can be mediated by altered concentrations of T3 (3,3',5-triiodo-L-thyronine), which regulates gene expression in the brain microenvironment, affecting neurogenesis, angiogenesis, neurotransmitter release, and synaptic transmission. Diminished TSH (thyrotropin) signalling may also impair learning and memory by inhibiting the Wnt5a-β-catenin pathway. Thyroid disorders may also contribute to neurodegeneration by T3-mediated attenuation of amyloid-β elimination or TRH-induced formation of neurofibrillary tangles. Surprisingly, most clinical studies do not specify the immune origin of hypothyroidism or hyperthyroidism, therefore further studies involving large, well-characterised patient cohorts are needed to clarify the relationships between AITD and cognitive impairments and psychiatric disorders. Furthermore, data on the effect of anti-thyroid antibodies on brain function are scarce and inconclusive. Given the association between hyperthyroidism and an increased risk of dementia, cognitive impairment and mood disorders, adequate treatment and careful monitoring of AITD patients are essential to prevent the induction of exogenous hyperthyroidism.
自身免疫性甲状腺疾病（AITD）是最常见的器官特异性自身免疫性疾病，包括格雷夫斯病（通常与甲状腺功能亢进有关）和桥本甲状腺炎（一般与甲状腺功能减退有关）。越来越多的证据表明，AITD会干扰脑功能。在此，我们通过分析临床、动物、离体和体外研究的数据，综述AITD对认知、情绪和精神障碍的影响，以揭示AITD影响脑功能的分子机制。大多数报告表明，认知障碍与甲状腺功能亢进（包括与AITD相关的）之间的关联比与甲状腺功能减退之间的关联更强。甲状腺功能减退和甲状腺功能亢进都与更高的抑郁症风险相关。至少其中一些影响可由T3（3,3',5-三碘-L-甲状腺原氨酸）浓度的改变介导，T3可调节脑微环境中的基因表达，影响神经发生、血管生成、神经递质释放和突触传递。促甲状腺激素（TSH）信号减弱也可能通过抑制Wnt5a-β-连环蛋白途径损害学习和记忆。甲状腺疾病也可能通过T3介导的淀粉样β蛋白清除减弱或促甲状腺激素释放激素（TRH）诱导的神经纤维缠结形成导致神经退行性变。令人惊讶的是，大多数临床研究并未明确甲状腺功能减退或亢进的免疫起源，因此需要进一步开展涉及大型、特征明确的患者队列的研究，以阐明AITD与认知障碍和精神障碍之间的关系。此外，关于抗甲状腺抗体对脑功能影响的数据稀缺且尚无定论。鉴于甲状腺功能亢进与痴呆、认知障碍和情绪障碍风险增加之间的关联，对AITD患者进行充分治疗和密切监测对于预防外源性甲状腺功能亢进的发生至关重要。
