Effect of rejection sensitivity on the development of anxious-depressive attack in Japanese outpatients: The mediating roles of rumination, social anxiety, and depressive symptoms.

Objective: Anxious-depressive attack (ADA) is a cluster of symptoms, including sudden and intense anxiety or depression, intrusive rumination about negative memories or future worries, prominent agitation, impatient behavior, and/or loneliness; in some cases, symptoms include a wide range of violent coping behaviors to manage emotional distress. Four characteristics-rejection sensitivity, rumination, social anxiety symptoms, and depressive symptoms-are thought to be associated with the development of ADA. However, the complex relationships among these factors have not been clarified. In this study, we aimed to examine the mechanism by which these four characteristics influence the development of ADA. Methods: We conducted a structured interview about ADA with 332 outpatients, who completed several self-report measures, to assess rejection sensitivity, rumination, social anxiety symptoms, and depressive symptoms. Results: A structural equation model showed goodness-of-fit with the data. These findings suggest that rejection sensitivity may demonstrate a direct effect on the occurrence of ADA. Furthermore, rejection sensitivity might affect depressive symptoms through rumination and social anxiety symptoms and consequently contribute to the development of ADA. Conclusion: These results provide preliminary evidence that rejection sensitivity contributes to the development of ADA.

L1cam is crucial for cell locomotion and terminal translocation of the Soma in radial migration during murine corticogenesis.

L1cam (L1) is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well-known being X-linked hydrocephalus. Although we recently demonstrated that L1 plays an important role in neuronal migration during cortical histogenesis, the mechanisms of delayed migration have still not been clarified. In this study, we found that cell locomotion in the intermediate zone and terminal translocation in the primitive cortical zone (PCZ) were affected by L1-knockdown (L1-KD). Time-lapse analyses revealed that L1-KD neurons produced by in utero electroporation of shRNA targeting L1 (L1-shRNAs) molecules showed decreased locomotion velocity in the intermediate zone, compared with control neurons. Furthermore, L1-KD neurons showed longer and more undulated leading processes during translocation through the primitive cortical zone. The curvature index, a quantitative index for curvilinearity, as well as the length of the leading process, were increased, whereas the somal movement was decreased in L1-KD neurons during terminal translocation in the PCZ. These results suggest that L1 has a role in radial migration of cortical neurons.

Downregulation of L1 perturbs neuronal migration and alters the expression of transcription factors in murine neocortex.

L1 is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well-known being X-linked hydrocephalus. L1 knockout (L1-KO) mice have revealed a variety of functions of L1 that were crucial in brain development in different brain regions. However; the function of L1 in neuronal migration during cortical histogenesis remains to be clarified. We therefore investigated the corticogenesis of mouse embryos in which L1 molecules were knocked down in selected neurons, by employing in utero electroporation with shRNAs targeting L1 (L1 shRNA). Although more than 50% of the cells transfected with no small hairpin RNA (shRNA; monster green fluorescent protein: MGFP only) vector at embryonic day 13 (E13) reached the cortical plate at E16, significantly fewer (27%) cells transfected with L1 shRNA migrated to the same extent. At E17, 22% of cells transfected with the MGFP-only vector were found in the intermediate zone, and significantly more (34%) cells transfected with L1 shRNA remained in the same zone. Furthermore, the directions of the leading process of neurons transfected with L1 shRNA became more dispersed compared with cells with the MGFP-only vector. In addition, two transcription factors expressed in the neurons, Satb2 and Tbr1, were shown to be reduced or aberrantly expressed in neurons transfected with L1 shRNA. These observations suggest that L1 plays an important role in regulating the locomotion and orientation of migrating neurons and the expression of transcription factors during neocortical development that might partially be responsible for the abnormal tract formation seen in L1-KO mice.