孤独症、双相情感障碍等精神疾病严重危害人类健康，神经黏附分子在精神疾病的发生中有着重要作用。申请人前期研究发现两个孤独症患者同时存在打断CNTN4基因的CNV；构建CNTN4基因敲除鼠进一步研究发现：CNTN4特异性表达于脑组织中并在皮层中具有较高表达；CNTN4-/-小鼠在开场实验、明暗箱实验以及高架十字迷宫中都表现出焦虑降低；在强迫游泳、悬尾实验中表现出抑郁降低；CNTN4-/-小鼠前额叶皮层中GluR1的表达较WT小鼠降低，成熟树突棘数量较WT小鼠减少，前额叶皮层II-III层的mEPSC频率和幅度降低。我们认为CNTN4可能通过参与突触的形成及神经发育，调控精神疾病的发生。本研究拟进一步利用细胞模型、CNTN4基因敲除小鼠和转基因小鼠等，阐明该基因在神经发育中的功能和导致精神疾病的分子机制。本研究将为精神疾病的诊疗提供潜在靶点及理论依据。

Psychiatric disorders, such as autism and bipolar disorder, are common illnesses that seriously affect human health. Neural cell adhesion molecules play an important role in the pathogenesis of these disorders. We previously identified two Chinese subjects with autism with copy number variations that disrupt Contactin 4 (CNTN4). We further demonstrated that CNTN4 was exclusively expressed in the brain, especially in the prefrontal cortex. We made CNTN4 knockout (CNTN4-/-) mice and found that CNTN4-/- mice showed reduced anxiety-like behaviors in open field, light dark box and elevated plus maze tests; CNTN4-/- mice also showed reduced depression-like behaviors in forced swimming and tail suspension tests. The expression of AMPAR subunit GluR1 in the prefrontal cortex was reduced in CNTN4-/- mice, and CNTN4-/- mice had less mature spines in layer II/III pyramidal cells (PCs) of the prefrontal cortex. The mEPSC frequency and amplitude in PCs of the prefrontal cortex was reduced in CNTN4-/- mice. Based on these results, we postulate that CNTN4 was involved in synaptogenesis and neural development, regulating the pathogenesis of psychiatric disorders. We propose to clarify the function of CNTN4 in neural development and the molecular mechanism of CNTN4 in the pathogenesis of psychiatric disorders. Our study could potentially provide new insights into the treatment of psychiatric disorders by offering new molecular mechanism in psychiatric disorders.