Tsiouris John A, Flory Michael
George A. Jervis Clinic, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, United States.
Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, NY, United States.
Front Psychiatry. 2023 Mar 16;14:1123279. doi: 10.3389/fpsyt.2023.1123279. eCollection 2023.
Cyclic adenosine monophosphate (cAMP) levels in the lymphoblasts and leukocytes of patients with major depressive disorder (MDD) have been reported to be downregulated compared to in controls. cAMP is a derivative of adenosine triphosphate (ATP), and low ATP turnover has been reported in the state of hypometabolism associated with human MDD and with mammalian hibernation due to suppression of mitochondrial metabolism. Similarities have been noted between many state-dependent neurobiological changes associated with MDD in humans and with mammalian hibernation.
To compare cAMP levels between human MDD and mammalian hibernation and to investigate whether cAMP downregulation is another state-dependent neurobiological finding, we measured cAMP concentrations in lysed leukocytes, plasma, and serum in serial blood specimens from nine female captive black bears (; CBBs), and cortisol levels in serum from 10 CBBs.
Cortisol levels were significantly higher during hibernation in CBBs, confirming previous findings in hibernating black bears and similar to findings in humans with MDD. cAMP levels were significantly lower during hibernation versus active states (pre-hibernation and exit from hibernation) and were similar to the cAMP downregulation reported in MDD patients versus euthymic patients or controls. cAMP level changes during the different states (hibernation, pre-hibernation, active) confirm their state-dependent status.
These findings are similar to the neurobiological findings associated with the hypometabolism (metabolic depression) observed during mammalian hibernation and reported during MDD. A sudden increase in cAMP levels was observed before entrance into pre-hibernation and during exit from hibernation. Further investigation is suggested into the possible role of elevated cAMP levels in initiation of the chain reaction of changes in gene expression, proteins, and enzymes leading to the suppression of mitochondrial metabolism and to low ATP turnover. This process leads to hypometabolism, the old adaptive mechanism that is used by organisms for energy preservation and is associated with both mammalian hibernation and human MDD.
据报道，与对照组相比，重度抑郁症（MDD）患者的淋巴细胞和白细胞中的环磷酸腺苷（cAMP）水平下调。cAMP是三磷酸腺苷（ATP）的衍生物，并且在与人类MDD相关的低代谢状态以及由于线粒体代谢受抑制而导致的哺乳动物冬眠状态下，已报道ATP周转率较低。已注意到人类MDD相关的许多状态依赖性神经生物学变化与哺乳动物冬眠之间存在相似之处。
为了比较人类MDD与哺乳动物冬眠之间的cAMP水平，并研究cAMP下调是否是另一种状态依赖性神经生物学发现，我们测量了9只圈养雌性黑熊（CBBs）连续血液样本中裂解白细胞、血浆和血清中的cAMP浓度，以及10只CBBs血清中的皮质醇水平。
CBBs在冬眠期间皮质醇水平显著更高，证实了先前对冬眠黑熊的研究结果，并且与MDD患者的研究结果相似。与活跃状态（冬眠前和冬眠结束时）相比，冬眠期间cAMP水平显著更低，并且与MDD患者与心境正常患者或对照组相比报道的cAMP下调相似。不同状态（冬眠、冬眠前、活跃）期间的cAMP水平变化证实了它们的状态依赖性。
这些发现与在哺乳动物冬眠期间观察到并在MDD期间报道的与低代谢（代谢抑制）相关的神经生物学发现相似。在进入冬眠前和冬眠结束时观察到cAMP水平突然升高。建议进一步研究cAMP水平升高在引发导致线粒体代谢抑制和ATP周转率降低的基因表达、蛋白质和酶变化的连锁反应中的可能作用。这个过程导致低代谢，这是生物体用于保存能量的古老适应性机制，并且与哺乳动物冬眠和人类MDD都相关。
