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研究生:李子蘋
研究生(外文):Tzu-Ping Lee
論文名稱:以Akt1基因缺損小鼠模式探討思覺失調症之性別差異-以行為測驗及核糖核酸測序進行研究
論文名稱(外文):Investigation of Sex Differences of Schizophrenia in Akt1-Deficient Mouse Model Using Behavioral Evaluation and RNA-Sequence Analysis
指導教授:賴文崧賴文崧引用關係
口試委員:Bin Xu陳倩瑜陳儀莊郭柏秀
口試委員(外文):Bin Xu
口試日期:2019-11-09
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:心理學研究所
學門:社會及行為科學學門
學類:心理學類
論文種類:學術論文
論文出版年:2019
畢業學年度:108
語文別:英文
論文頁數:162
中文關鍵詞:思覺失調症Akt1性別差異紋狀體多巴胺核糖核酸測序DESeq2Enrichr反轉錄即時聚合酶連鎖反應
外文關鍵詞:Schizophreniasex differenceAkt1striatumdopamineRNA-sequencingDESeq2EnrichrRT-qPCR
DOI:10.6342/NTU201904384
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思覺失調症為一嚴重的精神疾病且有著複雜的基因致病因素。在過去諸多研究中顯示,思覺失調症有明顯的性別差異,其中包含疾病盛行率、發病年齡、症狀以及對於藥物的反應。然而思覺失調症之性別差異的分子機轉至今仍未被詳細的研究,此類研究可提供重要的資訊,使思覺失調症進一步的被瞭解。在不同族群的人類基因研究中,AKT1 (protein kinase B α) 被發現與思覺失調症的致病機轉有關聯,為該疾病的候選基因之一。Akt1基因缺損小鼠被發現有類思覺失調症的特徵且展現出性別差異。除此之外,AKT1也是多巴胺受體D2的下游;AKT1的異常會導致多巴胺訊息傳遞鏈的缺損,進而引發行為上的異常。因此Akt1基因缺損小鼠是研究思覺失調症與其性別差異的合適動物模式。在本研究中的第一部分中,行為測驗被用於檢驗Akt1異形和子 (Akt1+/-) 小鼠的性別差異。行為測驗發現Akt1+/-公鼠表現較高的酬賞敏感度;母鼠則是對甲基安非他命有較高敏感度,但Akt1+/-母鼠相較於野生型母鼠(Wildtype)則對甲基安非他命有較低敏感度。為了要瞭解Akt1基因缺損小鼠的性別差異之分子機制,使用了次世代RNA定序 (RNA-sequencing) 去分析Akt1基因缺損小鼠的紋狀體之基因表現。基因表現量差異是使用DESeq2進行分析,發現帶有Akt1基因缺損後的公母鼠之間具有顯著表現量差異的基因數量變多 (WT♂vs. WT♀: 14 DE genes; Akt1+/-♂ vs. Akt1+/-♀: 322)。而相較於公鼠,母鼠表現出更多具有顯著表現量差異的基因 (WT♂vs. Akt1+/-♂: 18; WT♀vs. Akt1+/-♀: 119)。此外,有92個基因的表現量有顯著交互作用。基因功能分類(gene ontology)以及分子路徑 (pathway analysis) 分析結果顯示公鼠 (WT♂vs. Akt1+/-♂) 中受到Akt1基因缺損影響的生物性功能為免疫以及細胞間交互作用 (cell-cell interaction),而母鼠 (WT♀vs. Akt1+/-♀) 則是mRNA (messenger RNA) 相關調控機制則是受到最顯著的影響。最後,RT-qPCR結果顯示,Akt1+/-母鼠表現出較高的予基因轉錄現象有關的基因 (Hipk3, Ankrd10, Map4k5)。除此之外,在多巴胺相關 (Prprn2, Tspan7) 及Akt/Akt1相關 (Cadm2, Bmi1, Lnp) 的基因表現量上亦有顯著的性別差異。本篇研究所提出的發現可為Akt1基因缺損小鼠之性別差異提供其背後的分子機制,但仍須進一步的實驗去證實以及探索。
Schizophrenia is a severe mental disorder with complex genetic composition. Sex differences in schizophrenia are widely reported in the prevalence of disease, age of onset, symptoms, and responses to antipsychotics. However, the underlying molecular mechanism of the sex differences remain elusive, and a better understanding may provide new ways of treatment and/or insights to the disorder. Accumulating evidences from human genetic studies suggests that AKT1 (protein kinase B α), a key signaling kinase downstream of dopamine receptor D2 (DRD2), is associated with schizophrenia in several ethnic groups and it is one of the susceptibility genes which contribute to the pathogenesis of the disorder. Intriguingly, Akt1-deficient mice exhibited some characteristics of schizophrenia and sex differences were also reported in the Akt1-deficient mouse model, making it a suitable model to study not only schizophrenia but also its sex differences. In this thesis, behavior tests confirmed the sex differences of Akt1 heterozygous mutant mice (Akt1+/-), results showed higher reward sensitivity in male Akt1+/- mice (sucrose preference test) and higher sensitivity to methamphetamine in female mice (methamphetamine-induced behavioral sensitization). To further understand the molecular mechanism behind the sexual differences in Akt1+/- mice and their wild-type (WT) littermate controls, RNA-sequencing technique was used in this study. Transcriptomic expression of striatum tissues from male and female early adult mice were analyzed, due to previous reports of abnormal striatal DRD2 activity of Akt1+/- mice. Differential expression analysis revealed that Akt1-deficiency increased the sex differences of gene expression profile (WT♂vs. WT♀: 14 differentially expressed (DE) genes; Akt1+/-♂ vs. Akt1+/-♀: 322), and female mice displayed more DE genes than male mice when comparing to WT mice of each sex (WT♂vs. Akt1+/-♂: 18; WT♀vs. Akt1+/-♀: 119). Furthermore, there are 92 genes that display interaction effects of the two factors. Gene ontology and pathway analysis showed altered immune-related functions and cell-cell interaction in male mice, while mRNA regulations are more affected in female mice. Results of gene validation with RT-qPCR indicates possible altered transcriptional activity in Akt1+/- female mice (Hipk3, Ankrd10, Map4k5). Sex differences in dopamine-related genes may reveal the sex differences observed in behavioral evaluations (Prprn2, Tspan7). Genes related to Akt/Akt1 also demonstrated sex differences (Cadm2, Bmi1, Lnp). Genes and gene lists reported by this study could be candidates for the mechanism of sex differences behind Akt1-deficient mouse model of schizophrenia. Further experiments are needed to confirm the roles of each gene and test possible molecular actions.
1. Introduction pg. 1
1.1 Schizophrenia and Its Sex Differences pg. 1
1.2 Akt1-Deficeint Mouse Model as a Research Tool for Schizophrenia pg. 16
1.3 Application of RNA-Sequencing on Schizophrenia Research pg. 25
1.4 Objectives of This Thesis pg. 30
2. Materials and Method pg. 33
2.1 Animals pg. 33
2.2 Behavioral Evaluation pg. 33
2.3 RNA-Sequencing pg. 35
2.4 Reverse Transcription Real-Time Quantitative PCR (RT-qPCR) pg. 38
2.5 Statistical Analysis pg. 39
3. Results pg. 41
3.1 Behavioral Evaluation pg. 41
3.2 RNA-Sequencing pg. 46
3.3 Reverse Transcription Real-Time Quantitative PCR (RT-qPCR) pg. 54
4. Discussion pg. 61
4.1 Behavioral Evaluations Reveal Possible Sex Differences in The Dopaminergic Systems of Akt1+/- Male and Female Mice pg. 62
4.2 Akt Interaction with Estradiol Signaling Transduction Pathway Could Be a Possible Explanation to Increased Differential Gene Expression in The Striatum of Female Akt1+/- Mice Observed in RNA-Sequence Data pg. 68
4.3 Female Akt1+/- Mice Display Increased Expression of Genes Associated with Transcription Regulation pg. 72
4.4 Sex Difference in Expression of Genes Associated with DA-Related Functions May Reveal Possible Mechanism Behind the Sex Differences of Behaviors pg. 75
4.5 Genes Associated with Akt1 Display Sex Differences pg. 77
4.6 Principal Component Analysis Reveal Possible Outliers that Require Further Analysis pg. 79
4.7 Limitations, Future Directions and Conclusions pg. 82
5. References pg. 87
6. Figures and Tables pg. 123
7. Supplementary Figures and Tables pg. 149
Abdouh, M., Chatoo, W., El Hajjar, J., David, J., Ferreira, J., & Bernier, G. (2012). Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons. PloS One, 7, e31870. doi:10.1371/journal.pone.0031870
Abekawa, T., Ohmori, T., & Koyam, T. (1994). Effects of repeated administration of a high dose of methamphetamine on dopamine and glutamate release in rat striatum and nucleus accumbens. Brain Research, 276-281.
Abel, K. M., Drake, R., & Goldstein, J. M. (2010). Sex differences in schizophrenia. International Review of Psychiatry, 22, 417-428. doi:10.3109/09540261.2010.515205
Abi-Dargham, A., Gil, R., Krystal, J., Baldwin, R. M., Seibyl, J. P., Bowers, M., . . . Laruelle, M. (1998). Increased striatal dopamine transmission in schizophrenia: Confirmation in a second cohort. American Journal of Psychiatry, 155, 761-767. doi:10.1176/ajp.155.6.761
Abi-Dargham, A., Rodenhiser, J., Printz, D., Zea-Ponce, Y., Gil, R., Kegeles, L. S., . . . Laruelle, M. (2000). Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 97, 8104–8109. doi:10.1073/pnas.97.14.8104
Afshari, P., Yao, W. D., & Middleton, F. A. (2017). Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: Implications for schizophrenia. PloS One, 12, e0183854. doi:10.1371/journal.pone.0183854
Agid, O., Mamo, D., Ginovart, N., Vitcu, I., Wilson, A. A., Zipursky, R. B., & Kapur, S. (2007). Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response--a double-blind PET study in schizophrenia. Neuropsychopharmacology, 32, 1209-1215. doi:10.1038/sj.npp.1301242
Akama, K. T., & McEwen, B. S. (2003). Estrogen stimulates postsynaptic Density-95 Rapid Protein synthesis via the Akt/Protein Kinase B pathway. The Journal of Neuroscience, 23, 2333–2339. doi:https://doi.org/10.1523/JNEUROSCI.23-06-02333.2003
Aleman, A., Kahn, R. S., & Selten, J.-P. (2003). Sex differences in the risk of schizophrenia: Evidence from meta-analysis. Archives of General Psychiatry, 60, 565-571. doi:10.1001/archpsyc.60.6.565
Arguello, P. A., & Gogos, J. A. (2008). A signaling pathway AKTing up in schizophrenia. Journal of Clinical Investigation, 118, 2018-2021. doi:10.1172/JCI35931
Bassani, S., Cingolani, L. A., Valnegri, P., Folci, A., Zapata, J., Gianfelice, A., . . . Passafaro, M. (2012). The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking. Neuron, 73, 1143-1158. doi:10.1016/j.neuron.2012.01.021
Beaulieu, J. M., Sotnikova, T. D., Marion, S., Lefkowitz, R. J., Gainetdinov, R. R., & Caron, M. G. (2005). An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell, 122, 261-273. doi:10.1016/j.cell.2005.05.012
Beaulieu, J. M., Sotnikova, T. D., Yao, W.-D., Kockeritz, L., Woodgett, J. R., Gainetdinov, R. R., & Caron, M. G. (2004). Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proceedings of the National Academy of Sciences of the United States of America, 101, 5099–5104. doi:10.1073/pnas.0307921101
Beaulieu, J. M., Tirotta, E., Sotnikova, T. D., Masri, B., Salahpour, A., Gainetdinov, R. R., . . . Caron, M. G. (2007). Regulation of Akt signaling by D2 and D3 dopamine receptors in vivo. Journal of Neuroscience, 27, 881-885. doi:10.1523/JNEUROSCI.5074-06.2007
Becker, J. B., Molenda, H., & Hummer, D. L. (2001). Gender differences in the behavioral responses to cocaine and amphetamine: Implications for mechanisms mediating gender differences in drug abuse. Annals of the New York Academy of Sciences, 937, 172-187. doi:10.1111/j.1749-6632.2001.tb03564.x
Bergemann, N., Mundt, C., Parzer, P., Jannakos, I., Nagl, I., Salbach, B., . . . Resch, F. (2005). Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics. Schizophrenia Research, 73, 357-366. doi:10.1016/j.schres.2004.06.013
Bergemann, N., Parzer, P., Nagl, I., Salbach, B., Runnebaum, B., Mundt, C., & Resch, F. (2002). Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Archives of Women''s Mental Health, 5, 119-126. doi:10.1007/s00737-002-0004-2
Bergemann, N., Parzer, P., Runnebaum, B., Resch, F., & Mundt, C. (2007). Estrogen, menstrual cycle phases, and psychopathology in women suffering from schizophrenia. Psychological Medicine, 37, 1427-1436. doi:10.1017/S0033291707000578
Bigos, K. L., Pollock, B. G., Coley, K. C., Miller, D. D., Marder, S. R., Aravagiri, M., . . . Bies, R. R. (2008). Sex, race, and smoking impact olanzapine exposure. Journal of Clinical Pharmacology, 48, 157-165. doi:10.1177/0091270007310385
Bleuler, E. (1911). Dementia Praecox oder Gruppe der Schizophrenien. Leipzig, Germany: Deuticke.
Bozikas, V. P., Kosmidis, M. H., Peltekis, A., Giannakou, M., Nimatoudis, I., Karavatos, A., . . . Garyfallos, G. (2010). Sex differences in neuropsychological functioning among schizophrenia patients. Australian and New Zealand Journal of Psychiatry, 333-341. doi:10.3109/00048670903489833
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., . . . Gage, F. H. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473, 221-225. doi:10.1038/nature09915
Brown, A. S., Begg, M. D., Gravenstein, S., Schaefer, C. A., Wyatt, R. J., Bresnahan, M., & Susser, V. P. B. S. (2004). Serologic evidence of prenatal influenza in the etiology of schizophrenia. Archives of General Psychiatry, 61, 774-780. doi:10.1001/archpsyc.61.8.774
Brown, A. S., & Derkits, E. J. (2010). Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. American Journal of Psychiatry, 167, 20. doi:10.1176/appi.ajp.2009.09030361
Cadet, J. L., Brannock, C., Jayanthi, S., & Krasnova, I. N. (2015). Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: Evidence from a long-access self-administration model in the rat. Molecular Neurobiology, 51, 696-717. doi:10.1007/s12035-014-8776-8
Cantor-Graae, E., & Selten, J.-P. (2005). Schizophrenia and migration: A meta-analysis and review. American Journal of Psychiatry, 162, 12–24. doi:10.1176/appi.ajp.162.1.12
Cardno, A. G., & Gottesman, I. I. (2000). Twin studies of schizophrenia: From bow-and-arrow concordances to Star Wars Mx and functional genomics. American Journal of Medical Genetics, 97, 12-17.
Carlsson, A., & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica, 20, 140-144.
Caromile, L. A., Oganesian, A., Coats, S. A., Seifert, R. A., & Bowen-Pope, D. F. (2010). The neurosecretory vesicle protein phogrin functions as a phosphatidylinositol phosphatase to regulate insulin secretion. Journal of Biological Chemistry, 285, 10487-10496. doi:10.1074/jbc.M109.066563
Carrillo, J. A., & Benitez, J. (1996). CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine. British Journal of Clinical Pharmacology, 41, 605–608. doi:10.1046/j.1365-2125.1996.35418.x
Castle, D., Sham, P., & Murray, R. (1998). Differences in distribution of ages of onset in males and females with schizophrenia. Schizophrenia Research, 33, 179-183. doi:10.1016/s0920-9964(98)00070-x
Catts, V. S., Wong, J., Fillman, S. G., Fung, S. J., & Shannon Weickert, C. (2014). Increased expression of astrocyte markers in schizophrenia: Association with neuroinflammation. Australian and New Zealand Journal of Psychiatry, 48, 722-734. doi:10.1177/0004867414531078
Charil, A., Laplante, D. P., Vaillancourt, C., & King, S. (2010). Prenatal stress and brain development. Brain Research Reviews, 65, 56-79. doi:10.1016/j.brainresrev.2010.06.002
Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., . . . Ma’ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics, 14, 128. doi:10.1186/1471-2105-14-128
Chen, P. C., & Chen, J. C. (2005). Enhanced Cdk5 activity and p35 translocation in the ventral striatum of acute and chronic methamphetamine-treated rats. Neuropsychopharmacology, 30, 538-549. doi:10.1038/sj.npp.1300604
Chen, Y. C., Chen, Y. W., Hsu, Y. F., Chang, W. T., Hsiao, C. K., Min, M. Y., & Lai, W. S. (2012). Akt1 deficiency modulates reward learning and reward prediction error in mice. Genes, Brain, and Behavior, 11, 157-169. doi:10.1111/j.1601-183X.2011.00759.x
Chen, Y. W., Kao, H. Y., Min, M. Y., & Lai, W. S. (2014). A sex- and region-specific role of Akt1 in the modulation of methamphetamine-induced hyperlocomotion and striatal neuronal activity: Implications in schizophrenia and methamphetamine-induced psychosis. Schizophrenia Bulletin, 40, 388-398. doi:10.1093/schbul/sbt031
Chen, Y. W., & Lai, W. S. (2011). Behavioral phenotyping of v-akt murine thymoma viral oncogene homolog 1-deficient mice reveals a sex-specific prepulse inhibition deficit in females that can be partially alleviated by glycogen synthase kinase-3 inhibitors but not by antipsychotics. Neuroscience, 174, 178-189. doi:10.1016/j.neuroscience.2010.09.056
Chiang, C. H., Su, Y., Wen, Z., Yoritomo, N., Ross, C. A., Margolis, R. L., . . . Ming, G. L. (2011). Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Molecular Psychiatry, 16, 358-360. doi:10.1038/mp.2011.13
Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., & Birnbaum, M. J. (2001). Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. Journal of Biological Chemistry, 276, 38349-38352. doi:10.1074/jbc.C100462200
Chong, H. Y., Teoh, S. L., Wu, D. B., Kotirum, S., Chiou, C. F., & Chaiyakunapruk, N. (2016). Global economic burden of schizophrenia: A systematic review. Neuropsychiatric Disease and Treatment, 12, 357-373. doi:10.2147/NDT.S96649
Cohen, R. Z., Seeman, M. V., Gotowiec, A., & Kopala, L. (1999). Earlier puberty as a predictor of later onset of schizophrenia in women. American Journal of Psychiatry, 156, 1059–1064. doi:10.1176/ajp.156.7.1059
Creese, I., Burt, D. R., & Snyder, S. H. (1976). Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drug. Science, 192, 481-483. doi:10.1126/science.3854
Crowhurst, B., & Coles, E. M. (1989). Kurt Schneider''s concepts of psychopathy and schizophrenia: A review of the english literature. The Canadian Journal of Psychiatry, 34, 238-243.
Davies, Q., Welham, J., Chant, D., Torrey, E. F., & McQrath, J. (2003). A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophrenia Bulletin, 29, 587-593. doi:10.1093/oxfordjournals.schbul.a007030
Davis, K. L., Kahn, R. S., Ko, G., & Davidson, M. (1991). Dopamine in schizophrenia: A review and reconceptualization. American Journal of Psychiatry, 148, 1474-1486. doi:10.1176/ajp.148.11.1474
Debnath, M., & Berk, M. (2014). Th17 pathway-mediated immunopathogenesis of schizophrenia: Mechanisms and implications. Schizophrenia Bulletin, 40, 1412-1421. doi:10.1093/schbul/sbu049
DeLisi, L. E., Dauphinais, I. D., & Hauser, P. (1989). Gender differences to the pathogenesis in the brain: Are they relevant of schizophrenia? Comprehensive Psychology, 30, 197-208. doi:10.1016/0010-440x(89)90038-2
Denley, M. C. S., Gatford, N. J. F., Sellers, K. J., & Srivastava, D. P. (2018). Estradiol and the development of the cerebral cortex: An unexpected role? Frontiers in Neuroscience, 12, 245. doi:10.3389/fnins.2018.00245
Duclot, F., & Kabbaj, M. (2015). The estrous cycle surpasses sex differences in regulating the transcriptome in the rat medial prefrontal cortex and reveals an underlying role of early growth response 1. Genome Biology, 16, 256. doi:10.1186/s13059-015-0815-x
Duong, B. N., Elliott, S., Frigo, D. E., Melnik, L. I., Vanhoy, L., Tomchuck, S., . . . Burow, M. E. (2006). AKT regulation of estrogen receptor beta transcriptional activity in breast cancer. Cancer Research, 66, 8373-8381. doi:10.1158/0008-5472.CAN-05-3845
Edwards, A. C., Bacanu, S. A., Bigdeli, T. B., Moscati, A., & Kendler, K. S. (2016). Evaluating the dopamine hypothesis of schizophrenia in a large-scale genome-wide association study. Schizophrenia Research, 176, 136-140. doi:10.1016/j.schres.2016.06.016
Efimova, E. V., Gainetdinov, R. R., Budygin, E. A., & Sotnikova, T. D. (2016). Dopamine transporter mutant animals: A translational perspective. Journal of Neurogenetics, 30, 5-15. doi:10.3109/01677063.2016.1144751
Emamian, E. S., Hall, D., Birnbaum, M. J., Karayiorgou, M., & Gogos, J. A. (2004). Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nature Genetics, 36, 131-137. doi:10.1038/ng1296
Farrell, M. S., Werge, T., Sklar, P., Owen, M. J., Ophoff, R. A., O''Donovan, M. C., . . . Sullivan, P. F. (2015). Evaluating historical candidate genes for schizophrenia. Molecular Psychiatry, 20, 555-562. doi:10.1038/mp.2015.16
Fevr, T., Robine, S., Louvard, D., & Huelsken, J. (2007). Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Molecular and Cellular Biology, 27, 7551-7559. doi:10.1128/MCB.01034-07
Fillman, S. G., Cloonan, N., Catts, V. S., Miller, L. C., Wong, J., McCrossin, T., . . . Weickert, C. S. (2013). Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Molecular Psychiatry, 18, 206-214. doi:10.1038/mp.2012.110
Fogel, A. I., Akins, M. R., Krupp, A. J., Stagi, M., Stein, V., & Biederer, T. (2007). SynCAMs organize synapses through heterophilic adhesion. Journal of Neuroscience, 27, 12516-12530. doi:10.1523/JNEUROSCI.2739-07.2007
Frankle, W. G., & Laruelle, M. (2002). Neuroreceptor imaging in psychiatric disorders. Annals of Nuclear Medicine, 16, 437-446. doi:10.1007/bf02988639
Freyberg, Z., Ferrando, S. J., & Javitch, J. A. (2010). Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. American Journal of Psychiatry, 167, 388-396. doi:10.1176/appi.ajp.2009.08121873
Gejman, P. V., Sanders, A. R., & Kendler, K. S. (2011). Genetics of schizophrenia: New findings and challenges. Annual Review of Genomics and Human Genetics, 12, 121-144. doi:10.1146/annurev-genom-082410-101459
Gogos, A., Sbisa, A. M., Sun, J., Gibbons, A., Udawela, M., & Dean, B. (2015). A role for estrogen in schizophrenia: Clinical and preclinical findings. International Journal of Endocrinology, 2015, 615356. doi:10.1155/2015/615356
Gokce, O., Stanley, G. M., Treutlein, B., Neff, N. F., Camp, J. G., Malenka, R. C., . . . Quake, S. R. (2016). Cellular taxonomy of the mouse striatum as revealed by single-cell RNA-seq. Cell Reports, 16, 1126-1137. doi:10.1016/j.celrep.2016.06.059
Goldstein, J. M., Cohen, L. S., Hortond, N. J., Lee, H., Andersenf, S., Tohen, M., . . . Tollefsonf, G. (2002). Sex differences in clinical response to olanzapine compared with haloperidol. Psychiatry Research, 110, 27-37. doi:10.1016/s0165-1781(02)00028-8
Goldstein, J. M., Seidman, L. J., Goodman, J. M., Lee, D. K., Weintraub, S., & Tsuang, M. T. (1998). Are there sex differences in neuropsychological functions among patients with schizophrenia? American Journal of Psychiatry, 155, 1358–1364. doi:10.1176/ajp.155.10.1358
Goodwill, H. L., Manzano-Nieves, G., Gallo, M., Lee, H. I., Oyerinde, E., Serre, T., & Bath, K. G. (2019). Early life stress leads to sex differences in development of depressive-like outcomes in a mouse model. Neuropsychopharmacology, 44, 711-720. doi:10.1038/s41386-018-0195-5
Greenwood, T. A., Lazzeroni, L. C., Murray, S. S., Cadenhead, K. S., Calkins, M. E., Dobie, D. J., . . . Braff, D. L. (2011). Analysis of 94 Candidate Genes and 12 endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia. American Journal of Psychiatry, 168, 930–946. doi:10.1176/appi.ajp.2011.10050723
Halari, R., Kumari, V., Mehrotra, R., Wheeler, M., Hines, M., & Sharma, T. (2004). The relationship of sex hormones and cortisol with cognitive functioning in schizophrenia. Journal of Psychopharmacology, 18, 366–374. doi:10.1177/026988110401800307
Hallonquist, J. D., Seeman, M. V., Lang, M., & Rector, N. A. (1993). Variation in symptom severity over the menstrual cycle of schizophrenics. Biological Psychiatry, 33, 207-209. doi:10.1016/0006-3223(93)90141-y
Haro, J. M., Ciudad, A., Alonso, J., Bousoño, M., Suárez, D., Novick, D., & Gilaberte, I. (2008). Remission and relapse in the ambulatory treatment of patients with schizophrenia. Outcomes at 3 years. Actas Españolas de Psiquiatría, 36, 187-196.
Henriksen, M. G., Nordgaard, J., & Jansson, L. B. (2017). Genetics of schizophrenia: Overview of methods, findings and limitations. Frontiers in Human Neuroscience, 11, 322. doi:10.3389/fnhum.2017.00322
Hers, I., Vincent, E. E., & Tavare, J. M. (2011). Akt signalling in health and disease. Cellular Signalling, 23, 1515-1527. doi:10.1016/j.cellsig.2011.05.004
Hill, R. A. (2016). Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology. Neuroscience and Biobehavioral Reviews, 67, 41-56. doi:10.1016/j.neubiorev.2015.10.014
Hoff, A. L., Wieneke, M., Faustman, W. O., Horon, R., Sakuma, M., Blankfeld, H., . . . DeLisi, L. E. (1998). Sex differences in neuropsychological functioning of first-episode and chronically ill schizophrenic patients. American Journal of Psychiatry, 1437–1439. doi:10.1176/ajp.155.10.1437
Häfner, H. (2003). Gender differences in schizophrenia. Psychoneuroendocrinology, 28, 17-54. doi:10.1016/s0306-4530(02)00125-7
Howes, O. D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: Version III--the final common pathway. Schizophrenia Bulletin, 35, 549-562. doi:10.1093/schbul/sbp006
Howes, O. D., McCutcheon, R., Owen, M. J., & Murray, R. M. (2017). The role of genes, stress, and dopamine in the development of schizophrenia. Biological Psychiatry, 81, 9-20. doi:10.1016/j.biopsych.2016.07.014
Howes, O. D., Montgomery, A. J., Asselin, M. C., Murray, R. M., Valli, I., Tabraham, P., . . . Grasby, P. M. (2009). Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Archives of General Psychiatry, 66, 13-20. doi:10.1001/archgenpsychiatry.2008.514
Huelsken, J., & Behrens, J. (2002). The Wnt signalling pathway. Journal of Cell Science, 115, 3977-3978. doi:10.1242/jcs.00089
Huo, C., Liu, X., Zhao, J., Zhao, T., Huang, H., & Ye, H. (2018). Abnormalities in behaviour, histology and prefrontal cortical gene expression profiles relevant to schizophrenia in embryonic day 17 MAM-Exposed C57BL/6 mice. Neuropharmacology, 140, 287-301. doi:10.1016/j.neuropharm.2018.07.030
Hwang, Y., Kim, J., Shin, J. Y., Kim, J. I., Seo, J. S., Webster, M. J., . . . Kim, S. (2013). Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia. Translational Psychiatry, 3, 1-9. doi:10.1038/tp.2013.94
Ibrahim-Verbaas, C. A., Bressler, J., Debette, S., Schuur, M., Smith, A. V., Bis, J. C., . . . Mosley, T. H. (2016). GWAS for executive function and processing speed suggests involvement of the CADM2 gene. Molecular Psychiatry, 21, 189-197. doi:10.1038/mp.2015.37
Ikeda, M., Iwata, N., Suzuki, T., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., . . . Ozaki, N. (2004). Association of AKT1 with schizophrenia confirmed in a Japanese population. Biological Psychiatry, 56, 698-700. doi:10.1016/j.biopsych.2004.07.023
Imaizumi, Y., & Okano, H. (2014). Modeling human neurological disorders with induced pluripotent stem cells. Journal of Neurochemistry, 129, 388-399. doi:10.1111/jnc.12625
International Human Genome Sequencing Consortium. (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860-921. doi:10.1038/35057062
Ishihara, Y., Takemoto, T., Ishida, A., & Yamazaki, T. (2015). Protective actions of 17beta-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds. Oxidative Medicine and Cellular Longevity, 2015, 343706. doi:10.1155/2015/343706
Jablensky, A. (2010). The diagnostic concept of schizophrenia: Its history, evolution, and future prospects. Dialogues Clin Neurosci., 12, 271-287.
James, S. L., Abate, D., Abate, K. H., Abay, S. M., Abbafati, C., Abbasi, N., . . . Murray, C. J. L. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392, 1789-1858. doi:10.1016/s0140-6736(18)32279-7
Jin, H., & Mosweu, I. (2017). The societal cost of schizophrenia: A systematic review. Pharmacoeconomics, 35, 25-42. doi:10.1007/s40273-016-0444-6
Kendler, K. S., & Dlehl, S. R. (1993). The geneics of schizophrenia: A current, genetic-epidemiologic perspective. Schizophrenia Bulletin, 19, 261-285. doi:10.1093/schbul/19.2.261
Kestler, L. P., Walker, E., & Vega, E. M. (2001). Dopamine receptors in the brains of schizophrenia patients: A meta-analysis of the findings. Behavioral Pharmacology, 12, 355-371. doi:10.1097/00008877-200109000-00007
Kim, J. J., Mandelli, L., Lim, S., Lim, H. K., Kwon, O. J., Pae, C. U., . . . Jun, T. Y. (2008). Association analysis of heat shock protein 70 gene polymorphisms in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 258, 239-244. doi:10.1007/s00406-007-0791-6
Kokras, N., & Dalla, C. (2014). Sex differences in animal models of psychiatric disorders. British Journal of Pharmacology, 171. doi:10.1111/bph.2014.171.issue-20
Krentzel, A. A., & Meitzen, J. (2018). Biological sex, estradiol and striatal medium spiny neuron physiology: A mini-review. Frontiers in Cellular Neuroscience, 12, 492. doi:10.3389/fncel.2018.00492
Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., . . . Ma''ayan, A. (2016). Enrichr: A comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Research, 44, W90-97. doi:10.1093/nar/gkw377
Kumar, S., Patel, R., Moore, S., Crawford, D. K., Suwanna, N., Mangiardi, M., & Tiwari-Woodruff, S. K. (2013). Estrogen receptor beta ligand therapy activates PI3K/Akt/mTOR signaling in oligodendrocytes and promotes remyelination in a mouse model of multiple sclerosis. Neurobiology of Disease, 56, 131-144. doi:10.1016/j.nbd.2013.04.005
Lai, W.-S., Xu, B., Westphal, K. G. C., Paterlini, M., Olivier, B., Pavlidis, P., . . . Gogos, J. A. (2006). Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning. Proceedings of the National Academy of Sciences of the United States of America, 106, 16906–16911. doi:10.1073/pnas.0604994103
Lee, J. H., Huynh, M., Silhavy, J. L., Kim, S., Dixon-Salazar, T., Heiberg, A., . . . Gleeson, J. G. (2012). De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nature Genetics, 44, 941-945. doi:10.1038/ng.2329
Lee, S. A., Suh, Y., Lee, S., Jeong, J., Kim, S. J., Kim, S. J., & Park, S. K. (2017). Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking. FASEB Journal, 31, 2301-2313. doi:10.1096/fj.201600755RR
Leucht, S., Burkard, T., Henderson, J., Maj, M., & Sartorius, N. (2007). Physical illness and schizophrenia: A review of the literature. Acta Psychiatrica Scandinavica, 116, 317-333. doi:10.1111/j.1600-0447.2007.01095.x
Leung, A., & Chue, P. (2000). Sex differences in schizophrenia, a review of the literature. Acta Psychiatrica Scandinavica, 100, 3-38. doi:10.1111/j.0065-1591.2000.0ap25.x
Levenga, J., Wong, H., Milstead, R. A., Keller, B. N., LaPlante, L. E., & Hoeffer, C. A. (2017). AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity. Elife, 6, 1-24. doi:10.7554/eLife.30640
Levine, S. Z., Levav, I., Yoffe, R., & Pugachova, I. (2014). The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia. Schizophrenia Research, 158, 236-240. doi:10.1016/j.schres.2014.07.003
Li, R., Ma, X., Wang, G., Yang, J., & Wang, C. (2016). Why sex differences in schizophrenia? Journal of Translational Neuroscience (Beijing), 1, 37–42.
Li, X., Chen, D., Li, M., Gao, X., Shi, G., & Zhao, H. (2018). The CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in esophageal squamous cell carcinoma cells. Chemico-Biological Interactions, 288, 76-82. doi:10.1016/j.cbi.2018.04.021
Li, X., & Teng, S. (2015). RNA Sequencing in Schizophrenia. Bioinformatics and Biology Insights, 9, 53-60. doi:10.4137/BBI.S28992
Lieberman, J. A., Kane, J. M., & Alvir, J. (1987). Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology, 91, 415-433. doi:10.1007/bf00216006
Limanaqi, F., Gambardella, S., Biagioni, F., Busceti, C. L., & Fornai, F. (2018). Epigenetic effects induced by methamphetamine and methamphetamine-dependent oxidative stress. Oxidative Medicine and Cellular Longevity, 2018, 4982453. doi:10.1155/2018/4982453
Lin, M., Hrabovsky, A., Pedrosa, E., Wang, T., Zheng, D., & Lachman, H. M. (2012). Allele-biased expression in differentiating human neurons: Implications for neuropsychiatric disorders. PloS One, 7, e44017. doi:10.1371/journal.pone.0044017
Lin, M., Zhao, D., Hrabovsky, A., Pedrosa, E., Zheng, D., & Lachman, H. M. (2014). Heat shock alters the expression of schizophrenia and autism candidate genes in an induced pluripotent stem cell model of the human telencephalon. PloS One, 9, e94968. doi:10.1371/journal.pone.0094968
Lin, X. H., Hashimoto, T., Kitamura, N., Murakami, N., Shirakawa, O., & Maeda, K. (2002). Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine. Synapse, 44, 181-187. doi:10.1002/syn.10071
Lindstrom, L. H., Gefvert, O., Hagberg, G., Lundberg, T., Bergstrom, M., Hartvig, P., & Långstrom, B. (1999). Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-DOPA and PET. Biological Psychiatry, 46, 681-688. doi:10.1016/s0006-3223(99)00109-2
Liu, Y., Liu, F., Yu, H., Zhao, X., Sashida, G., Deblasio, A., . . . Nimer, S. D. (2012). Akt phosphorylates the transcriptional repressor Bmi1 to block its effects on the tumor-suppressing Ink4a-Arf locus. Science Signaling, 5, 1-11. doi:10.1126/scisignal.2003199
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-408. doi:10.1006/meth.2001.1262
Love, M. I., Huber, W., & Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15, 550. doi:10.1186/s13059-014-0550-8
Luo, D.-Z. (2014). The involvement of Akt1 in the regulation of striatal dopamine D2 receptor activity and the rescue effect of lithium on akt1-related behavioral deficits in akt1 mutant mice model of schizophrenia. (Unpublished Master''s thesis), National Taiwan University, Taipei, Taiwan.
Lyon, E. R. (1999). A review of the effects of nicotine on schizophrenia and antipsychotic medications. Psychiatry Services, 50, 1346-1350. doi:10.1176/ps.50.10.1346
Maatz, A., & Hoff, P. (2014). The birth of schizophrenia or a very modern Bleuler: A close reading of Eugen Bleuler’s ‘Die Prognose der Dementia praecox’ and a re-consideration of his contribution to psychiatry. History of Psychiatry, 25, 431 –440. doi:10.1177/0957154X14546606
Manning, B. D., & Toker, A. (2017). AKT/PKB signaling: Navigating the network. Cell, 169, 381-405. doi:10.1016/j.cell.2017.04.001
March, D., Hatch, S. L., Morgan, C., Kirkbride, J. B., Bresnahan, M., Fearon, P., & Susser, E. (2008). Psychosis and place. Epidemiologic Reviews, 30, 84-100. doi:10.1093/epirev/mxn006
Marcotte, E. R., Pearson, D. M., & Srivastava, L. K. (2001). Animal models of schizophrenia: A critical review. Journal of Psychiatry and Neuroscience, 26, 395-410.
Markham, J. A. (2012). Sex steroids and schizophrenia. Reviews in Endocrine & Metabolic Disorders, 13, 187-207. doi:10.1007/s11154-011-9184-2
McCarthy, M. M. (2008). Estradiol and the developing brain. Physiological Reviews, 88, 91-124. doi:10.1152/physrev.00010.2007
McGlashan, T. H., & Bardenstein, K. K. (1990). Gender differences in affective, schizoaffective, and schizophrenic disorders. 16, 319-329. doi:10.1016/0920-9964(90)90034-5
McGowan, S., Lawrence, A., Sales, T., Quested, D., & Grasby, P. (2004). Presynaptic dopaminergic dysfunction in schizophrenia: A Positron Emission Tomographic [18F]Fluorodopa study. Archives of General Psychiatry, 61, 134-142. doi:10.1001/archpsyc.61.2.134
McGrath, J., Saha, S., Chant, D., & Welham, J. (2008). Schizophrenia: A concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews, 30, 67-76. doi:10.1093/epirev/mxn001
McGrath, J., & Scott, J. (2011). Urban birth and risk of schizophrenia: A worrying example of epidemiology where the data are stronger than the hypotheses. Epidemiology and Psychiatric Sciences, 15, 243-246. doi:10.1017/s1121189x00002104
Moriarty, P. J., Lieber, D., Bennett, A., White, L., Parrella, M., Harvey, P. D., & Davis, K. L. (2001). Gender differences in poor outcome patients with lifelong schizophrenia. Schizophrenia Bulletin, 27, 103-113. doi:10.1093/oxfordjournals.schbul.a006850
Mudge, J., Miller, N. A., Khrebtukova, I., Lindquist, I. E., May, G. D., Huntley, J. J., . . . Kingsmore, S. F. (2008). Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum. PloS One, 3, e3625. doi:10.1371/journal.pone.0003625
Nacerddine, K., Beaudry, J. B., Ginjala, V., Westerman, B., Mattiroli, F., Song, J. Y., . . . van Lohuizen, M. (2012). Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer. Journal of Clinical Investigation, 122, 1920-1932. doi:10.1172/JCI57477
Ng, M. Y., Levinson, D. F., Faraone, S. V., Suarez, B. K., DeLisi, L. E., Arinami, T., . . . Lewis, C. M. (2009). Meta-analysis of 32 genome-wide linkage studies of schizophrenia. Molecular Psychiatry, 14, 774-785. doi:10.1038/mp.2008.135
Nie, J., Wang, H., He, F., & Huang, H. (2010). Nusap1 is essential for neural crest cell migration in zebrafish. Protein Cell, 1, 259-266. doi:10.1007/s13238-010-0036-8
Nilsson, M. E., Vandenput, L., Tivesten, A., Norlen, A. K., Lagerquist, M. K., Windahl, S. H., . . . Ohlsson, C. (2015). Measurement of a comprehensive sex steroid profile in rodent serum by High-Sensitive Gas Chromatography-Tandem Mass Spectrometry. Endocrinology, 156, 2492-2502. doi:10.1210/en.2014-1890
Nordentoft, M., Thorup, A., Petersen, L., Ohlenschlaeger, J., Melau, M., Christensen, T. O., . . . Jeppesen, P. (2006). Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial. A randomized clinical trial of integrated treatment and standard treatment. Schizophrenia Research, 83, 29-40. doi:10.1016/j.schres.2006.01.002
Norman, R. M., Malla, A. K., Manchanda, R., & Townsend, L. (2005). Premorbid adjustment in first episode schizophrenia and schizoaffective disorders: A comparison of social and academic domains. Acta Psychiatrica Scandinavica, 112, 30-39. doi:10.1111/j.1600-0447.2005.00555.x
O''Neill, C. (2013). PI3-kinase/Akt/mTOR signaling: impaired on/off switches in aging, cognitive decline and Alzheimer''s disease. Experimental Gerontology, 48, 647-653. doi:10.1016/j.exger.2013.02.025
Os, J. v., & Selten, J.-P. (1998). Prenatal exposure to maternal stress and subsequent schizophrenia: The May 1940 invasion of The Netherlands. British Journal of Psychiatry, 171, 314-316. doi:10.1192/bjp.172.4.324
Patel, N. H., Vyas, N. S., Puri, B. K., Nijran, K. S., & Al-Nahhas, A. (2010). Positron emission tomography in schizophrenia: A new perspective. Journal of Nuclear Medicine, 51, 511-520. doi:10.2967/jnumed.109.066076
Pooley, A. E., Benjamin, R. C., Sreedhar, S., Eagle, A. L., Robison, A. J., Mazei-Robison, M. S., . . . Jordan, C. L. (2018). Sex differences in the traumatic stress response: The role of adult gonadal hormones. Biology of Sex Differences, 9, 32. doi:10.1186/s13293-018-0192-8
Prokai-Tatrai, K., & Prokai, L. (2018). 17β-Estradiol as a neuroprotective agent. In G. Drevensek (Ed.), Sex hormones in neurodegenerative processes and diseases (pp. 21-39). Slovenia: IntechOpen.
Raemaekers, T., Ribbeck, K., Beaudouin, J., Annaert, W., Van Camp, M., Stockmans, I., . . . Carmeliet, G. (2003). NuSAP, a novel microtubule-associated protein involved in mitotic spindle organization. Journal of Cell Biology, 162, 1017-1029. doi:10.1083/jcb.200302129
Ratnayake, U., & Hill, R. A. (2016). Studies on the effects prenatal immune activation on postnatal behavior: Models of developmental origins of schizophrenia. In D. W. Walker (Ed.), Prenatal and postnatal determinants of development (Vol. 109, pp. 263-278). New York, NY, USA: Humana Press.
Rosso, S. B., & Inestrosa, N. C. (2013). WNT signaling in neuronal maturation and synaptogenesis. Frontiers in Cellular Neuroscience, 7, 1-11. doi:10.3389/fncel.2013.00103
Rudge, S. A., & Wakelam, M. J. (2016). Phosphatidylinositolphosphate phosphatase activities and cancer. Journal of Lipid Research, 57, 176-192. doi:10.1194/jlr.R059154
Šagud, M., Mihaljević-Peleš, A., Mück-Šeler, D., Pivac, N., Vuksan-Ćusa, B., Brataljenović, T., & Jakovljević, M. (2009). Smoking and Schizophrenia. Psychiatria Danubina, 21, 371–375.
Sale, E. M., & Sale, G. J. (2008). Protein kinase B: signalling roles and therapeutic targeting. Cellular and Molecular Life Sciences, 65, 113-127. doi:10.1007/s00018-007-7274-9
Schijndel, J. E. V., & Martens, G. J. M. (2010). Gene expression profiling in rodent models for schizophrenia. Current Neuropharmacology, 8, 382-393. doi:10.2174/157015910793358132
Schizophrenia Working Group of the Psychiatric Genomics, C. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511, 421-427. doi:10.1038/nature13595
Schwab, S. G., Hoefgen, B., Hanses, C., Hassenbach, M. B., Albus, M., Lerer, B., . . . Wildenauer, D. B. (2005). Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families. Biological Psychiatry, 58, 446-450. doi:10.1016/j.biopsych.2005.05.005
Seeman, M. V. (1983). Interaction of sex, age, and neuroleptic dose. Comprehensive Psychiatry, 24, 1-4. doi:10.1016/0010-440x(83)90100-1
Seeman, M. V., & Lang, M. (1990). The role of estrogens in schizophrenia gender differences. Schizophrenia Bulletin, 16, 10. doi:10.1093/schbul/16.2.185
Seeman, P. (2013). Schizophrenia and dopamine receptors. European Neuropsychopharmacol, 23, 999-1009. doi:10.1016/j.euroneuro.2013.06.005
Seeman, P., Lee, T., Chau-Wong, M., & Wong, K. (1976). Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature, 261, 717-719.
Shi, C. S., Huang, N. N., Harrison, K., Han, S. B., & Kehrl, J. H. (2006). The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes. Molecular and Cellular Biology, 26, 6511-6521. doi:10.1128/MCB.00209-06
Stoica, G. E., Franke, T. F., Moroni, M., Mueller, S., Morgan, E., Iann, M. C., . . . Stoica, A. (2003). Effect of estradiol on estrogen receptor-alpha gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway. Oncogene, 22, 7998-8011. doi:10.1038/sj.onc.1206769
Stoica, G. E., Franke, T. F., Wellstein, A., Czubayko, F., List, H. J., Reiter, R., . . . Stoica, A. (2003). Estradiol rapidly activates Akt via the ErbB2 signaling pathway. Molecular Endocrinology, 17, 818-830. doi:10.1210/me.2002-0330
Sullivan, P. F. (2005). The genetics of schizophrenia. PLoS Medicine, 2, 614-618. doi:10.1371/journal.pmed.0020212
Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003). Schizophrenia as a complex trait: Evidence from a meta-analysis of twin studies. Archives of General Psychiatry, 60, 1187-1192. doi:10.1001/archpsyc.60.12.1187
Tang, Y. L., Mao, P., Li, F. M., Li, W., Chen, Q., Jiang, F., . . . Mitchell, P. B. (2007). Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia. British Journal of Clinical Pharmacology, 64, 49-56. doi:10.1111/j.1365-2125.2007.02852.x
Thiselton, D. L., Vladimirov, V. I., Kuo, P.-H., McClay, J., Wormley, B., Fanous, A., . . . Riley, B. P. (2008). AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish Study of High Density Schizophrenia Families (ISHDSF). Biological Psychiatry, 63, 449-457. doi:10.1016/j.biopsych.2007.06.005
Thomas, L. A., Akins, M. R., & Biederer, T. (2008). Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions. Journal of Comparative Neurology, 510, 47-67. doi:10.1002/cne.21773
Toyota, T., Yamada, K., Detera-Wadleigh, S. D., & Yoshikawa, T. (2003). Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees: A family-based association study. Neuroscience Letters, 339, 5-8. doi:10.1016/s0304-3940(02)01428-3
Tucker, L. B., Burke, J. F., Fu, A. H., & McCabe, J. T. (2017). Neuropsychiatric symptom modeling in male and female C57BL/6J mice after experimental traumatic brain injury. Journal of Neurotrauma, 34, 890-905. doi:10.1089/neu.2016.4508
Uggerby, P., Nielsen, R. E., Correll, C. U., & Nielsen, J. (2011). Characteristics and predictors of long-term institutionalization in patients with schizophrenia. Schizophrenia Research, 131, 120-126. doi:10.1016/j.schres.2011.03.001
Valjent, E., Pascoli, V., Svenningsson, P., Paul, S., Enslen, H., Corvol, J.-C., . . . Girault, J.-A. (2005). Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proceedings of the National Academy of Sciences of the United States of America, 102, 491–496. doi:10.1073/pnas.0408305102
van den Buuse, M. (2010). Modeling the positive symptoms of schizophrenia in genetically modified mice: Pharmacology and methodology aspects. Schizophrenia Bulletin, 36, 246-270. doi:10.1093/schbul/sbp132
Van Swearingen, A. E., Walker, Q. D., & Kuhn, C. M. (2013). Sex differences in novelty- and psychostimulant-induced behaviors of C57BL/6 mice. Psychopharmacology, 225, 707-718. doi:10.1007/s00213-012-2860-4
Wang, F., Yamauchi, M., Muramatsu, M., Osawa, T., Tsuchida, R., & Shibuya, M. (2011). RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3K/Akt pathway. Journal of Biological Chemistry, 286, 9097-9106. doi:10.1074/jbc.M110.165605
Wang, X., & Cairns, M. J. (2014). Understanding complex transcriptome dynamics in schizophrenia and other neurological diseases using RNA sequencing. International Review of Neurobiology, 116, 127-152. doi:10.1016/B978-0-12-801105-8.00006-0
Wang, Z., Gerstein, M., & Snyder, M. (2009). RNA-Seq: A revolutionary tool for transcriptomics. Nature Reveiws Genetics, 10, 57-63. doi:10.1038/nrg2484
Wearne, T. A., & Cornish, J. L. (2018). A comparison of methamphetamine-induced psychosis and schizophrenia: A review of positive, negative, and cognitive symptomatology. Frontiers in Psychiatry, 9, 1-21. doi:10.3389/fpsyt.2018.00491
Weinstein, J. J., Chohan, M. O., Slifstein, M., Kegeles, L. S., Moore, H., & Abi-Dargham, A. (2017). Pathway-specific dopamine abnormalities in schizophrenia. Biological Psychiatry, 81, 31-42. doi:10.1016/j.biopsych.2016.03.2104
Welch, W. J. (1991). The role of heat-shock proteins as molecular chaperones. Current Opinion in Cell Biology, 3, 1033-1038. doi:10.1016/0955-0674(91)90125-i
Wong, J., Woon, H. G., & Weickert, C. S. (2011). Full length TrkB potentiates estrogen receptor alpha mediated transcription suggesting convergence of susceptibility pathways in schizophrenia. Molecular and Cellular Neurosciences, 46, 67-78. doi:10.1016/j.mcn.2010.08.007
Wu, J. Q., Wang, X., Beveridge, N. J., Tooney, P. A., Scott, R. J., Carr, V. J., & Cairns, M. J. (2012). Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia. PloS One, 7, 1-14. doi:10.1371/journal.pone.0036351
Xu, J., Sun, J., Chen, J., Wang, L., Li, A., Helm, M., . . . Chen, X. (2012). RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia. BMC Genomics, 13, 1-10. doi:10.1186/1471-2164-13-S8-S2
Xu, M.-Q., Xing, Q.-H., Zheng, Y.-L., Li, S., Gao, J.-J., He, G., . . . He, L. (2007). Association of AKT1 gene polymorphisms with risk of schizophrenia and with response to antipsychotics in the Chinese population. Journal of Clinical Psychiatry, 68, 1358–1367. doi:10.4088/jcp.v68n0906
Xu, Z., Wang, Y., Xiong, J., Cui, F., Wang, L., & Peng, H. (2019). NUSAP1 knockdown inhibits cell growth and metastasis of non-small-cell lung cancer through regulating BTG2/PI3K/Akt signaling. Journal of Cellular Physiology, 1-8. doi:10.1002/jcp.29282
Yagi, S., Drewczynski, D., Wainwright, S. R., Barha, C. K., Hershorn, O., & Galea, L. A. M. (2017). Sex and estrous cycle differences in immediate early gene activation in the hippocampus and the dorsal striatum after the cue competition task. Hormones and Behavior, 87, 69-79. doi:10.1016/j.yhbeh.2016.10.019
Yang, X., Wang, Y., Li, Q., Zhong, Y., Chen, L., Du, Y., . . . Yan, J. (2018). The main molecular mechanisms underlying methamphetamine- induced neurotoxicity and implications for pharmacological treatment. Frontiers in Molecular Neuroscience, 11, 1-18. doi:10.3389/fnmol.2018.00186
Yui, K., Ikemoto, S., Ishiguro, T., & Goto, K. (2000). Studies of amphetamine or methamphetamine psychosis in Japan: relation of methamphetamine psychosis to schizophrenia. Annals of the New York Academy of Sciences, 914, 1-12. doi:10.1111/j.1749-6632.2000.tb05178.x
Zeng, L., Zhang, P., Shi, L., Yamamoto, V., Lu, W., & Wang, K. (2013). Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models. PloS One, 8, 1-11. doi:10.1371/journal.pone.0059685
Zhang, J., Han, L., Zhang, A., Wang, Y., Yue, X., You, Y., . . . Kang, C. (2010). AKT2 expression is associated with glioma malignant progression and required for cell survival and invasion. Oncology Reports, 24, 65-72. doi:10.3892/or_00000829
Zhao, J., Liu, X., Huo, C., Zhao, T., & Ye, H. (2018). Abnormalities in prefrontal cortical gene expression profiles relevant to schizophrenia in MK-801-exposed C57BL/6 mice. Neuroscience, 390, 60-78. doi:10.1016/j.neuroscience.2018.07.046
Zheng, W., Wang, H., Zeng, Z., Lin, J., Little, P. J., Srivastava, L. K., & Quirion, R. (2012). The possible role of the Akt signaling pathway in schizophrenia. Brain Research, 1470, 145-158. doi:10.1016/j.brainres.2012.06.032
Ziats, M. N., & Rennert, O. M. (2014). Identification of differentially expressed microRNAs across the developing human brain. Molecular Psychiatry, 19, 848-852. doi:10.1038/mp.2013.93
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