The etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by histone deacetylase (HDAC) enzymes. This study measures in vivo HDAC expression in individuals with BD for the first time using the HDAC-specific radiotracer [¹¹C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance – positron emission tomography (MR-PET) scan with [¹¹C]Martinostat. Lower [¹¹C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in schizophrenia and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [¹¹C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [¹¹C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [¹¹C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular, HDAC expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.

双相情感障碍 (BD) 的病因尚不清楚，神经生物学基础也不完全清楚。遗传和环境因素都会导致 BD 的风险，这可能与表观遗传机制有关，包括由组蛋白脱乙酰酶 (HDAC) 酶调节的机制。本研究首次使用 HDAC 特异性放射性示踪剂 [ ¹¹ C]Martinostat 测量 BD 患者的体内 HDAC 表达。^{11 名 BD 参与者和 11 名年龄和性别匹配的对照参与者 (CON) 使用 [ 11} C]Martinostat完成了同步磁共振 - 正电子发射断层扫描 (MR-PET) 扫描。下 [ ¹¹C] 与 CON 相比，在 BD 的右侧杏仁核中发现了 Martinostat 摄取。我们评估了背外侧前额叶皮层 (DLPFC) 的摄取，以比较先前在精神分裂症中 DLPFC 摄取较低的发现，并发现 BD 没有组间差异。探索性全脑体素分析显示，与 CON 相比，BD 中双侧丘脑、眶额皮质、右侧海马和右侧杏仁核的[ ^{11 C]Martinostat 摄取较低。}此外，区域性 [ ¹¹ C]Martinostat 摄取与 BD 额叶边缘区域的情绪调节有关，这与之前在 BD 中的结构、功能和分子神经影像学研究的结果一致。区域 [ ¹¹C]Martinostat 摄取与额顶叶和颞叶区域的 BD 注意力相关。这些发现表明 HDAC 在 BD 病理生理学中的潜在作用。特别是，HDAC 表达水平可以调节注意力和情绪调节，这代表了 BD 的两个核心临床特征。