School of Nursing, Peking University Health Science Center, Beijing, 100191, China; PKU-IDG/McGovern Institute for Brain Research, School of Life Sciences, Peking University, Beijing 100871, China.
School of Psychological and Cognitive Sciences and Beijing Key Laboratory of Behavior and Mental Health, Speech and Hearing Research Center, Key Laboratory on Machine Perception (Ministry of Education), Peking University, Beijing 100080, China.
Neuroscience. 2019 Apr 15;404:396-406. doi: 10.1016/j.neuroscience.2019.02.001. Epub 2019 Feb 8.
Prepulse inhibition (PPI) can be modulated by both the Val158Met (rs4680) polymorphism of the Catechol-O-Methyltransferase (COMT) gene and the menstrual-cycle-related hormone fluctuations, each of which affects the subcortical/cortical dopamine metabolism. PPI can also be modulated by attention. The attentional modulation of PPI (AMPPI) is sensitive to psychoses. Whether the Val158Met polymorphism affects the AMPPI in female adults at different menstrual-cycle phases is unknown. This study examined whether AMPPI and/or PPI are affected by the Val158Met polymorphism in 177 younger-adult females whose menstrual cycles were mutually different across the menstruation, proliferative, or secretory phases. The AMPPI was evaluated by comparing PPI under the condition of the auditory precedence-effect-induced perceptual spatial separation between the prepulse stimulus and a masking noise (PPI) against that under the condition of the precedence-effect-induced perceptual spatial co-location (PPI). The results showed that both the menstrual cycle and the COMT Val158Met polymorphism affected both PPI and PPI, but not the AMPPI (difference between PPI and PPI). Moreover, throughout the menstrual cycle, both PPI and PPI decreased monotonously in Val/Val-carrier participants. However, the decreasing pattern was not overserved in either Met/Met-carrier or Met/Val-carrier participants. Thus, in healthy younger-adult females, PPI and PPI, but not the AMPPI, is vulnerable to changes of ovarian hormones, and the COMT Val158Met polymorphism also has a modulating effect on this menstrual-cycle-dependent PPI variation. In contrast, the AMPPI seems to be more steadily trait-based, less vulnerable to ovarian hormone fluctuations, and may be useful in assisting the diagnosis of schizophrenia in female adults.
前脉冲抑制（PPI）可以被儿茶酚-O-甲基转移酶（COMT）基因的 Val158Met（rs4680）多态性和与月经周期相关的激素波动共同调节，这两者都会影响皮质下/皮质多巴胺代谢。PPI 也可以被注意力调节。PPI 的注意力调制（AMPPI）对精神病敏感。Val158Met 多态性是否会影响不同月经周期阶段女性成年人大脑中的 AMPPI 尚不清楚。本研究通过比较听觉优先效应诱导的 prepulse 刺激和掩蔽噪声之间的知觉空间分离（PPI）和知觉空间共定位（PPI）条件下的 PPI，检测了 177 名年轻成年女性的 AMPPI 是否受 Val158Met 多态性的影响，这些女性的月经周期处于月经期、增殖期或分泌期。结果表明，月经周期和 COMT Val158Met 多态性均影响 PPI 和 PPI，但不影响 AMPPI（PPI 和 PPI 之间的差异）。此外，在整个月经周期内，Val/Val 携带者的 PPI 和 PPI 均呈单调下降。然而，在 Met/Met 携带者或 Met/Val 携带者中并未观察到这种下降模式。因此，在健康的年轻成年女性中，PPI 和 PPI（而不是 AMPPI）易受卵巢激素变化的影响，COMT Val158Met 多态性也对这种与月经周期相关的 PPI 变化具有调节作用。相比之下，AMPPI 似乎更稳定，不易受到卵巢激素波动的影响，可能有助于对成年女性精神分裂症的诊断。
