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Akira Suda,1 Saki Hattori,1 Ikuko Kishida,1,2 Masatoshi Miyauchi,1 Yohko Shiraishi,1 Mami Fujibayashi,3 Natsuki Tsujita,4 Chie Ishii,2 Norio Ishii,2 Toshio Moritani,5 Yoshio Hirayasu1,6 1Department of Psychiatry, Yokohama City University School of Medicine, Yokohama, 2Department of Psychiatry, Fujisawa Hospital, Kanagawa, 3Division of Physical and Health Education, Setsunan University, Osaka, 4Graduate School of Human and Environmental Studies, Kyoto University, 5Department of Health and Sports Sociology, Faculty of General Education, Kyoto Sangyo University, Kyoto, 6Department of Psychiatry, Hirayasu Hospital, Okinawa, Japan Objective: Long-acting injections (LAIs) of antipsychotics show distinct pharmacokinetic profiles from oral antipsychotics (OAPs). Although there may be differences in adverse event frequency, any differences in their effects on autonomic nervous system (ANS) remain unclear. Patients and methods: In total, 270 schizophrenic patients were recruited in this study: 241 received OAPs (risperidone, olanzapine, quetiapine, or aripiprazole) and 29 received LAIs (risperidone LAI, aripiprazole LAI, or paliperidone palmitate) as monotherapy. Heart rate variability was measured as an index of ANS activity, and the low-frequency (0.03–0.15 Hz) component, high-frequency (0.15–0.40 Hz) component, and total power (0.03–0.40 Hz) were calculated. Components were compared between the groups using t-tests. Results: A significant difference was detected in the low-frequency component between the OAP and LAI groups (P=0.046). No significant difference was found in total power or the high-frequency component between the two groups. Conclusion: Compared with OAPs, LAIs have fewer adverse effects on ANS activity, particularly the low-frequency component, as determined using a spectral analysis of heart rate variability. Keywords: long-acting injectable antipsychotics, autonomic nervous system, heart rate variability, adverse effect

Nobutaka Hanagata,1,2 Xianglan Li,1 Min-Hua Chen,1 Jie Li,1 Shinya Hattori1 1Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, 2Graduate School of Life Science, Hokkaido University, Sapporo, Japan Abstract: Conventional class B cytosine-guanine (CpG) (CpG-B) oligodeoxynucleotide (ODNs) consisting of a single-stranded (ss) phosphorothioate (PT) backbone (ss CpG-B-PT) is converted from a proinflammatory cytokine inducer to a type-I interferon (IFN) inducer when complexed with cationic materials. In this study, we designed ss CpG-B and double-stranded (ds) CpG-B ODNs with a phosphodiester (PD) backbone (ss CpG-B-PD and ds CpG-B-PD, respectively) that became type-I IFN inducers upon complexation with Lipofectamine 2000 (Lipo), a cationic liposome. The ds CpG-B-PD complex induced higher IFN-β expression in mouse macrophage-like RAW264 cells than ss CpG-B-PD and ss CpG-B-PT complexes. The fold induction of IFN-β increased with the number of CpG motifs in ds CpG-B-PD, and a complex of ds CpG-B-PD consisting of 72 base pairs with nine CpG motifs (ds CpG-B72-PD) and Lipo showed the highest capacity to induce IFN-β. The materials and method used for complexation influenced the degree of IFN-β induction: ds CpG-B72-PD entrapped by calcium phosphate (CaP) (ds CpG-B72-PD/CaP) showed a higher induction capacity than ds CpG-B72-PD adsorbed onto the CaP surface. Entrapment of ds CpG-B72-PD by CaP also enhanced the induction of the proinflammatory cytokine interleukin-12. Vaccinating mice with ds CpG-B72-PD/CaP in conjunction with ovalbumin (OVA) increased the ratios of OVA-specific CD8+ T cells to total CD8+ T cells in peripheral blood and of OVA-specific IgG2a associated with helper T (Th)1 cells to OVA-specific IgG1 associated with Th2 cells. These results indicate that ds CpG-B72-PD/CaP is an effective vaccine adjuvant that can activate both cellular and Th1-type humoral immune responses. Keywords: CpG oligodeoxynucleotide, calcium phosphate, vaccine adjuvant, cellular immunity, humoral immunity