Many studies implicate altered cyclic nucleotide signaling in the pathophysiology of major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). As such, we explored how phosphodiesterases 2A (PDE2A) and 10A (PDE10A)-enzymes that break down cyclic nucleotides-may be altered in brains of these patients. Using autoradiographic in situ hybridization on postmortem brain tissue from the Stanley Foundation Neuropathology Consortium, we measured expression of PDE2 and PDE10 mRNA in multiple brain regions implicated in psychiatric pathophysiology, including cingulate cortex, orbital frontal cortex (OFC), superior temporal gyrus, hippocampus, parahippocampal cortex, amygdala, and the striatum. We also assessed how PDE2A and PDE10A expression changes in these brain regions across development using the Allen Institute for Brain Science Brainspan database. Compared to controls, patients with SCZ, MDD and BPD all showed reduced PDE2A mRNA in the amygdala. In contrast, PDE2A expression changes in frontal cortical regions were only significant in patients with SCZ, while those in caudal entorhinal cortex, hippocampus, and the striatum were most pronounced in patients with BPD. PDE10A expression was only detected in striatum and did not differ by disease group; however, all groups showed significantly less PDE10A mRNA expression in ventral versus dorsal striatum. Across development, PDE2A mRNA increased in these brain regions; whereas, PDE10A mRNA expression decreased in all regions except striatum. Thus, PDE2A mRNA expression changes in both a disorder- and brain region-specific manner, potentially implicating PDE2A as a novel diagnostic and/or patient-selection biomarker or therapeutic target.

中文翻译：

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磷酸二酯酶 PDE2A 和 PDE10A 都会随着年龄的增长而改变人脑中的 mRNA 表达，但只有 PDE2A 以特定于区域的方式在精神疾病中发生变化。

许多研究表明，重度抑郁症 (MDD)、双相情感障碍 (BPD) 和精神分裂症 (SCZ) 的病理生理学中环核苷酸信号的改变。因此，我们探索了磷酸二酯酶 2A (PDE2A) 和 10A (PDE10A) - 分解环核苷酸的酶 - 如何在这些患者的大脑中发生改变。使用来自 Stanley Foundation Neuropathology Consortium 的死后脑组织的放射自显影原位杂交，我们测量了 PDE2 和 PDE10 mRNA 在与精神病理生理学有关的多个脑区中的表达，包括扣带皮层、眶额叶皮层 (OFC)、颞上回、海马、海马旁皮质、杏仁核和纹状体。我们还使用艾伦脑科学研究所 Brainspan 数据库评估了这些大脑区域中 PDE2A 和 PDE10A 表达在整个发育过程中的变化。与对照组相比，SCZ、MDD 和 BPD 患者杏仁核中的 PDE2A mRNA 均减少。相比之下，额叶皮层区域的 PDE2A 表达变化仅在 SCZ 患者中显着，而在 BPD 患者中，尾内嗅皮层、海马和纹状体中的 PDE2A 表达变化最为明显。PDE10A 表达仅在纹状体中检测到，并且在疾病组之间没有差异；然而，与背侧纹状体相比，所有组在腹侧纹状体中的 PDE10A mRNA 表达显着减少。在整个发育过程中，这些大脑区域的 PDE2A mRNA 增加；而除纹状体外，所有区域的 PDE10A mRNA 表达均下降。因此，