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系統識別號 U0026-1508201616015600
論文名稱(中文) 以催產素及催產素受體基因多型性預測重鬱症患者服用抗憂鬱劑之治療反應
論文名稱(英文) Plasma oxytocin level and OXTR predict antidepressant treatment outcome in patients with major depressive disorder
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 104
學期 2
出版年 105
研究生(中文) 彭宜靖
研究生(英文) Yi-Chin Peng
學號 s66031073
學位類別 碩士
語文別 英文
論文頁數 157頁
口試委員 指導教授-張惠華
口試委員-陳柏熹
口試委員-周辰熹
中文關鍵字 抗憂鬱劑  重度憂鬱症  催產素  受體  基因多型性 
英文關鍵字 antidepressant  major depressive disorder  oxytocin  receptor  polymorphism 
學科別分類
中文摘要 研究背景: 重度憂鬱症患者的調控壓力系統失衡而產生憂鬱情緒,雖然使用抗憂鬱劑可以調整情緒,卻有部分人出現代謝異常。最近研究指出催產素-催產素受體系統可以降低壓力反應、調節能量、情緒及社交行為。此外,基因多型性可能牽涉到病患個體間是否產生代謝異常的現象,催產素受體基因多型性與重度憂鬱症及壓力反應有關。然而,目前尚未有研究針對催產素濃度及催產素受體基因多型性作為預測重度憂鬱症患者服用抗憂鬱劑後治療反應的指標。

目標:本研究探討(1)催產素濃度與臨床指標在健康人或重度憂鬱症病患的關聯,(2)催產素受體基因多型性對臨床指標在健康人或重度憂鬱症病患的關聯,(3)利用催產素濃度或催產素受體基因多型性預測重度憂鬱症病患使用抗憂鬱劑的治療反應。

材料與方法: 招募18到65歲符合精神疾病診斷與統計手冊第四版(DSM-IV)診斷為重度憂鬱症且漢氏憂鬱量表大於15分的病患。在簽署受試者同意書後,會被有受過訓練的精神科醫師收錄進本研究中。所有被收錄進來的病人都會隨機被分配到氟西汀組(Fluoxetine)或是文拉法辛組(Venlafaxine)。重鬱症患者在治療前及治療後第2、4、6週紀錄漢氏憂鬱量表。而治療前及治療後第6週測驗認知功能及抽取空腹靜脈血來檢測代謝指標及催產素濃度。除此之外,還會蒐集問卷,包括社會支持量表、生活事件量表及生活品質量表。而本研究也透過社區廣告招收健康受試者,對於以上測驗健康受試者皆會測量一次。

結果: 本研究收錄了111位重度憂鬱症病患及96位健康受試者。病人的平均年紀為39.4±12.6歲,健康受試者的平均年紀為33.3±12.1歲。病人有26.1%為男性,健康受試者則有42.7%為男性。在基本資料的分析,重度憂鬱症病患比健康受試者有較高的漢式憂鬱量表分數、空腹血糖、催產素濃度及C反應蛋白濃度。另外,重度憂鬱症病患比健康受試者有較低的體重、瘦素濃度、認知功能、社會支持量表分數及生活品質量表分數。在治療過後,重度憂鬱症病患的漢氏憂鬱量表分數顯著下降,且認知功能得到改善。然而,三酸甘油脂濃度及C反應蛋白濃度在治療後有上升的情形。結果1: 在健康受試者當中,催產素濃度顯著的與胰島素及穩態模型胰島素阻抗指數(The homeostasis model of assessment for insulin resistance, HOMA-IR)呈負相關。在病人當中則是治療後催產素濃度的改變量與穩態模型貝塔細胞功能指數(The homeostasis model of assessment for pancreatic β-cell secretory function, HOMA-β)的改變量呈正相關。結果2:健康受試者帶有GG基因型比帶有A對偶基因的人有較高的漢氏憂鬱量表分數及皮質固醇濃度。此外,病人帶有GG基因型的比帶有A對偶基因的人有較高的空腹血糖、醣化血色素及低密度蛋白質膽固醇濃度。治療後,病人帶有GG基因型的比帶有A對偶基因的人有較高的醣化血色素,但較低的催產素濃度。結果3:重度憂鬱症病人治療前的催產素濃度顯著的與治療後催產素濃度改變量呈負相關。另一方面,病人帶有GG基因型比帶有A對偶基因在治療後降低較多的膽固醇濃度及低密度蛋白質膽固醇濃度。帶有GG基因型的病人在藥物介入後會改善慣用手手指輕敲測驗的能力。帶有GG基因型的病人若是社會支持量表的分數越高,其醣化血色素在治療後下降的越多。

結論:健康受試者的催產素濃度越高會有越低的胰島素阻抗,但在重度憂鬱症病患身上卻沒有這個現象。除此之外,重度憂鬱症病患帶有GG基因型有較低的催產素濃度,但在治療後對代謝反應的調節更為敏感。因此,催產素濃度與催產素受體基因多型性對於調節能量是相當重要的。
英文摘要 Background: Major depressive disorder (MDD) patients have depressive mood caused by dysfunction of stress system. Patients regulate depressive mood through antidepressants, but some of them cause energy metabolic disturbance. Recent studies indicated that oxytocin - oxytocin receptors system has effect on reducing stress response as well as regulating energy, emotion and social process. Genetic factors may involve in individual difference. Oxytocin receptor polymorphism (OXTR) was associated with MDD and with stress response. However, there was no study focusing on oxytocin level and OXTR as predicting factors for antidepressant treatment outcome in MDD patients.

Aims: In this study, we aimed to investigate (1) the correlation between plasma oxytocin and clinical features in healthy controls and in MDD patients, (2) the association between OXTR and clinical features in healthy controls and in MDD patients, and (3) the prediction of treatment outcome by plasma oxytocin or OXTR after antidepressant treatment in patients with MDD.

Materials and Methods: Patients (aged 18–65 years) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th version (DSM-IV) for major depressive disorder, and Hamilton depression rating scale (HAMD) greater than 15 scores were enrolled consecutively by trained psychiatrists. MDD patients were randomly treated with fluoxetine or venlafaxine. MDD patients were assessed HAMD at baseline and week 2, 4, and 6. Cognitive function tests and fasting blood sample, detected metabolic indices and oxytocin level, were collected at baseline and after 6 weeks of treatment. In addition, we also collected questionnaire, including social support, life event scales and WHO quality of life. In addition, healthy controls were enrolled from community through advertisement.

Result: We recruited 131 MDD patients and 96 healthy controls in this study. The mean age of MDD patients and healthy controls were 39.4±12.6 and 33.3±12.1 years old, respectively. There were 26.9% male in MDD patients and 42.7% male in healthy controls. MDD patients had higher HAMD scores, fasting blood glucose, oxytocin level and CRP compared to controls. Moreover, MDD patients had lower weight, leptin, cognitive function test, social support scale and WHO quality of life than controls. After treatment, the HAMD scores and cognitive function were significant improved in MDD patients. However, TG and CRP were elevated. Result 1: Plasma oxytocin was negatively correlated with insulin and the homeostasis model of assessment for insulin resistance (HOMA-IR) in healthy controls. The change of oxytocin was positively correlated with the change of the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) in patients with MDD after treatment. Result 2: Controls with GG genotype had higher HAMD and cortisol than those with A allele. Moreover, patients with GG genotype had higher fasting blood sugar, HbA1c and LDL than those with A allele. After treatment, patients with GG genotype also had higher HbA1c and oxytocin. Result 3: Baseline oxytocin was negatively correlated with the change of oxytocin in MDD patients. On the other hand, patients with GG genotype decreased more cholesterol and LDL after treatment. Patients with GG genotype improved more dominant finger with FTT test by antidepressant intervention. Patients with GG genotype decreased more HbA1c by higher social support effect after treatment.

Conclusion: Our findings suggest that higher oxytocin level would have lower insulin resistance in healthy controls, but not in patients with MDD. In addition, patients with the GG genotype, whom have lower oxytocin level, were more sensitive to metabolic regulation from treatment. These findings also indicate that oxytocin level and OXTR are important moderators that shape metabolic features.
論文目次 中文摘要 I
Abstract III
致謝 V
Contents VI
Table of contents VII
Figure of contents X
Abbreviations XIII
1. Introduction 1
1.1 Major depressive disorder 1
1.2 Current pharmacological treatment of major depressive disorder 1
1.3 Antidepressant-related energy metabolism disturbance 2
1.4 Possible risk factors of disturbance energy metabolism in patient with MDD 2
1.5 Oxytocin – oxytocin receptor system 2
1.6 Oxytocin receptor gene (OXTR) 4
1.7 Pharmacogenomics 4
2. Objectives of current study 5
3. Materials and methods 6
3.1 Study design 6
3.2 Subjects and method 6
3.3 Measurements 6
3.4 Statistics 10
4. Results 11
4.1 Demographic features of patients and healthy controls 11
4.2 The correlation between plasma oxytocin level and clinical features 14
4.3 Association between the rs53576 of oxytocin receptor polymorphism (OXTR) and treatment outcome 16
4.4 Effect of antidepressants on treatment outcome 24
5. Discussion 128
5.1 The role of oxytocin system on major depressive disorder and energy homeostasis 128
5.2 The role of OXTR on major depressive disorder and energy homeostasis 132
5.3 Limitation 134
6. Conclusion 135
7. Reference 136
8. Appendix 142
參考文獻 Bagdy, G., & Kalogeras, K. T. (1993). Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat. Brain Res, 611(2), 330-332.
Camerino, C. (2009). Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity (Silver Spring), 17(5), 980-984.
Chen, F. S., Kumsta, R., von Dawans, B., Monakhov, M., Ebstein, R. P., & Heinrichs, M. (2011). Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans. Proc Natl Acad Sci U S A, 108(50), 19937-19942.
Chen, Y. C., Shen, Y. C., Hung, Y. J., Chou, C. H., Yeh, C. B., & Perng, C. H. (2007). Comparisons of glucose-insulin homeostasis following maprotiline and fluoxetine treatment in depressed males. J Affect Disord, 103(1-3), 257-261.
Costa, B., Pini, S., Gabelloni, P., Abelli, M., Lari, L., Cardini, A., . . . Martini, C. (2009). Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology, 34(10), 1506-1514.
Davidson, J. R. (2010). Major depressive disorder treatment guidelines in America and Europe. J Clin Psychiatry, 71 Suppl E1, e04.
De Long, N. E., Hyslop, J. R., Raha, S., Hardy, D. B., & Holloway, A. C. (2014). Fluoxetine-induced pancreatic beta cell dysfunction: New insight into the benefits of folic acid in the treatment of depression. Journal of Affective Disorders, 166(0), 6-13.
Deblon, N., Veyrat-Durebex, C., Bourgoin, L., Caillon, A., Bussier, A. L., Petrosino, S., . . . Rohner-Jeanrenaud, F. (2011). Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats. PLoS One, 6(9), e25565.
Dunning, B. E., Moltz, J. H., & Fawcett, C. P. (1984). Modulation of insulin and glucagon secretion from the perfused rat pancreas by the neurohypophysial hormones and by desamino-D-arginine vasopressin (DDAVP). Peptides, 5(5), 871-875.
Eaton, J. L., Roache, L., Nguyen, K. N., Cushing, B. S., Troyer, E., Papademetriou, E., & Raghanti, M. A. (2012). Organizational effects of oxytocin on serotonin innervation. Dev Psychobiol, 54(1), 92-97.
Emiliano, A. B., Cruz, T., Pannoni, V., & Fudge, J. L. (2007). The interface of oxytocin-labeled cells and serotonin transporter-containing fibers in the primate hypothalamus: a substrate for SSRIs therapeutic effects? Neuropsychopharmacology, 32(5), 977-988.
Garcia, F. D., Coquerel, Q., Kiive, E., Dechelotte, P., Harro, J., & Fetissov, S. O. (2011). Autoantibodies reacting with vasopressin and oxytocin in relation to cortisol secretion in mild and moderate depression. Prog Neuropsychopharmacol Biol Psychiatry, 35(1), 118-125.
Global burden of mental disorders and the need for a comprehensive, coordinated response from health and social sectors at the country level. (2012). http://apps.who.int/gb/ebwha/pdf_files/WHA65/A65_10-en.pdf
Heaton RK, C. G., Talley JL, Kay GG, Curtiss G. (1993). Wisconsin Card Sorting Test manual: Revised and expanded.: Odessa, FL: Psychological Assessment Resources.
Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003). Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry, 54(12), 1389-1398.
Jankowski, M., Bissonauth, V., Gao, L., Gangal, M., Wang, D., Danalache, B., . . . Gutkowska, J. (2010). Anti-inflammatory effect of oxytocin in rat myocardial infarction. Basic Res Cardiol, 105(2), 205-218.
Jorgensen, H., Kjaer, A., Knigge, U., Moller, M., & Warberg, J. (2003). Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides. J Neuroendocrinol, 15(6), 564-571.
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., . . . National Comorbidity Survey, R. (2003). The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA, 289(23), 3095-3105.
L. Pai, H.-C. W., R.-B. Lu, M.-L. Kuo. (1985). The questionnaire of life stress cognition of adults-revised (full text in Chinese).-. Chinese Journal of Mental Health (Taipei), 3, 195-205.
Lawson, E. A., Marengi, D. A., DeSanti, R. L., Holmes, T. M., Schoenfeld, D. A., & Tolley, C. J. (2015). Oxytocin reduces caloric intake in men. Obesity (Silver Spring), 23(5), 950-956.
Li, Q., Brownfield, M. S., Battaglia, G., Cabrera, T. M., Levy, A. D., Rittenhouse, P. A., & van de Kar, L. D. (1993). Long-term treatment with the antidepressants fluoxetine and desipramine potentiates endocrine responses to the serotonin agonists 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) and (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). J Pharmacol Exp Ther, 266(2), 836-844.
Li, Q., Levy, A. D., Cabrera, T. M., Brownfield, M. S., Battaglia, G., & Van de Kar, L. D. (1993). Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats. Brain Res, 630(1-2), 148-156.
Li, Q., Muma, N. A., & van de Kar, L. D. (1996). Chronic fluoxetine induces a gradual desensitization of 5-HT1A receptors: reductions in hypothalamic and midbrain Gi and G(o) proteins and in neuroendocrine responses to a 5-HT1A agonist. J Pharmacol Exp Ther, 279(2), 1035-1042.
Maejima, Y., Rita, R. S., Santoso, P., Aoyama, M., Hiraoka, Y., Nishimori, K., . . . Yada, T. (2015). Nasal oxytocin administration reduces food intake without affecting locomotor activity and glycemia with c-Fos induction in limited brain areas. Neuroendocrinology, 101(1), 35-44.
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28(7), 412-419.
McQuaid, R. J., McInnis, O. A., Abizaid, A., & Anisman, H. (2014). Making room for oxytocin in understanding depression. Neurosci Biobehav Rev, 45, 305-322.
Melis, M. R., Succu, S., Sanna, F., Boi, A., & Argiolas, A. (2009). Oxytocin injected into the ventral subiculum or the posteromedial cortical nucleus of the amygdala induces penile erection and increases extracellular dopamine levels in the nucleus accumbens of male rats. Eur J Neurosci, 30(7), 1349-1357.
Meynen, G., Unmehopa, U. A., Hofman, M. A., Swaab, D. F., & Hoogendijk, W. J. (2007). Hypothalamic oxytocin mRNA expression and melancholic depression. Mol Psychiatry, 12(2), 118-119.
Morton, G. J., Thatcher, B. S., Reidelberger, R. D., Ogimoto, K., Wolden-Hanson, T., Baskin, D. G., . . . Blevins, J. E. (2012). Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol Endocrinol Metab, 302(1), E134-144.
Nation, D. A., Szeto, A., Mendez, A. J., Brooks, L. G., Zaias, J., Herderick, E. E., . . . McCabe, P. M. (2010). Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE-/- mice. Psychosom Med, 72(4), 376-382.
Oliveira-Pelegrin, G. R., Saia, R. S., Carnio, E. C., & Rocha, M. J. (2013). Oxytocin affects nitric oxide and cytokine production by sepsis-sensitized macrophages. Neuroimmunomodulation, 20(2), 65-71.
Ozsoy, S., Esel, E., & Kula, M. (2009). Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Res, 169(3), 249-252.
Parker, K. J., Buckmaster, C. L., Schatzberg, A. F., & Lyons, D. M. (2005). Intranasal oxytocin administration attenuates the ACTH stress response in monkeys. Psychoneuroendocrinology, 30(9), 924-929.
Parker, K. J., Kenna, H. A., Zeitzer, J. M., Keller, J., Blasey, C. M., Amico, J. A., & Schatzberg, A. F. (2010). Preliminary evidence that plasma oxytocin levels are elevated in major depression. Psychiatry Res, 178(2), 359-362.
Purba, J. S., Hoogendijk, W. J., Hofman, M. A., & Swaab, D. F. (1996). Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry, 53(2), 137-143.
Rahe, C. D. R. R. H. (1975). Epidemiological Studies of Life Change and Illness. The International Journal of Psychiatry in Medicine, 6(1), 133-146.
Robinson, K. J., Hazon, N., Lonergan, M., & Pomeroy, P. P. (2014). Validation of an enzyme-linked immunoassay (ELISA) for plasma oxytocin in a novel mammal species reveals potential errors induced by sampling procedure. J Neurosci Methods, 226, 73-79.
Roffeei, S. N., Mohamed, Z., Reynolds, G. P., Said, M. A., Hatim, A., Mohamed, E. H., . . . Zainal, N. Z. (2014). Association of FTO, LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics. Pharmacogenomics, 15(4), 477-485.
Roh, S. G., Koiwa, K., Sato, K., Ohtani, Y., Takahashi, T., & Katoh, K. (2014). Actions of intravenous injections of AVP and oxytocin on plasma ACTH, GH, insulin and glucagon concentrations in goats. Anim Sci J, 85(3), 286-292.
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Stewart, J. W., Nierenberg, A. A., Thase, M. E., . . . Fava, M. (2006). Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med, 354(12), 1231-1242.
Rutigliano, G., Rocchetti, M., Paloyelis, Y., Gilleen, J., Sardella, A., Cappucciati, M., . . . Fusar-Poli, P. (2016). Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis. Psychiatry Res, 241, 207-220.
Saphire-Bernstein, S., Way, B. M., Kim, H. S., Sherman, D. K., & Taylor, S. E. (2011). Oxytocin receptor gene (OXTR) is related to psychological resources. Proc Natl Acad Sci U S A, 108(37), 15118-15122.
Saravani, R., Esmaeeli, E., Kordi Tamendani, M., & Nejad, M. N. (2015). Oxytocin Receptor Gene Polymorphisms in Patients With Diabetes. Gene, Cell and Tissue, 2(2), e27904.
Scantamburlo, G., Hansenne, M., Fuchs, S., Pitchot, W., Marechal, P., Pequeux, C., . . . Legros, J. J. (2007). Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology, 32(4), 407-410.
Seay, J. S., Lattie, E., Schneiderman, N., Antoni, M. H., Fekete, E. M., Mendez, A. J., . . . Fletcher, M. A. (2014). Linear and Quadratic Associations of Plasma Oxytocin With Depressive Symptoms in Ethnic Minority Women Living With HIV. Journal of Applied Biobehavioral Research, 19(1), 70-78.
Shimoyama, I., Ninchoji, T., & Uemura, K. (1990). The finger-tapping test: A quantitative analysis. Archives of Neurology, 47(6), 681-684.
Slattery, D. A., & Neumann, I. D. (2010). Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment. Pharmaceuticals, 3(3), 702-724.
Smid, H. G., de Witte, M. R., Homminga, I., & van den Bosch, R. J. (2006). Sustained and transient attention in the continuous performance task. J Clin Exp Neuropsychol, 28(6), 859-883.
Sokero, T. P., Melartin, T. K., Rytsala, H. J., Leskela, U. S., Lestela-Mielonen, P. S., & Isometsa, E. T. (2003). Suicidal ideation and attempts among psychiatric patients with major depressive disorder. J Clin Psychiatry, 64(9), 1094-1100.
Souza-Moreira, L., Campos-Salinas, J., Caro, M., & Gonzalez-Rey, E. (2011). Neuropeptides as pleiotropic modulators of the immune response. Neuroendocrinology, 94(2), 89-100.
Stratta, P., Mancini, F., Mattei, P., Daneluzzo, E., Casacchia, M., & Rossi, A. (1997). Association between Striatal Reduction and Poor Wisconsin Card Sorting Test Performance in Patients with Schizophrenia. Biological Psychiatry, 42(9), 816-820.
Streiner, D. L. (2014). Statistics commentary series: commentary #3--last observation carried forward. J Clin Psychopharmacol, 34(4), 423-425.
Szeto, A., McCabe, P. M., Nation, D. A., Tabak, B. A., Rossetti, M. A., McCullough, M. E., . . . Mendez, A. J. (2011). Evaluation of enzyme immunoassay and radioimmunoassay methods for the measurement of plasma oxytocin. Psychosom Med, 73(5), 393-400.
Takayanagi, Y., Kasahara, Y., Onaka, T., Takahashi, N., Kawada, T., & Nishimori, K. (2008). Oxytocin receptor-deficient mice developed late-onset obesity. Neuroreport, 19(9), 951-955.
Thompson, S. M., Hammen, C., Starr, L. R., & Najman, J. M. (2014). Oxytocin receptor gene polymorphism (rs53576) moderates the intergenerational transmission of depression. Psychoneuroendocrinology, 43, 11-19.
Tost, H., Kolachana, B., Hakimi, S., Lemaitre, H., Verchinski, B. A., Mattay, V. S., . . . Meyer-Lindenberg, A. (2010). A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function. Proc Natl Acad Sci U S A, 107(31), 13936-13941.
Uvnas-Moberg, K., Bjokstrand, E., Hillegaart, V., & Ahlenius, S. (1999). Oxytocin as a possible mediator of SSRI-induced antidepressant effects. Psychopharmacology (Berl), 142(1), 95-101.
Volkow, N. D., Gur, R. C., Wang, G. J., Fowler, J. S., Moberg, P. J., Ding, Y. S., . . . Logan, J. (1998). Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry, 155(3), 344-349.
Wang, L., McLeod, H. L., & Weinshilboum, R. M. (2011). Genomics and drug response. N Engl J Med, 364(12), 1144-1153.
Watanabe, S., Wei, F. Y., Matsunaga, T., Matsunaga, N., Kaitsuka, T., & Tomizawa, K. (2016). Oxytocin Protects against Stress-Induced Cell Death in Murine Pancreatic beta-Cells. Sci Rep, 6, 25185.
Weissman, M. M. (1996). Cross-National Epidemiology of Major Depression and Bipolar Disorder. JAMA: The Journal of the American Medical Association, 276(4), 293.
Welch, M. G., Margolis, K. G., Li, Z., & Gershon, M. D. (2014). Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice. Am J Physiol Gastrointest Liver Physiol, 307(8), G848-862.
Wu, C. S., Gau, S. S., & Lai, M. S. (2014). Long-term antidepressant use and the risk of type 2 diabetes mellitus: a population-based, nested case-control study in Taiwan. J Clin Psychiatry, 75(1), 31-38; quiz 38.
Yao, G., Chung, C. W., Yu, C. F., & Wang, J. D. (2002). Development and verification of validity and reliability of the WHOQOL-BREF Taiwan version. J Formos Med Assoc, 101(5), 342-351.
Yegen, B. (2010). Oxytocin and hypothalamo-pituitary adrenal axis. Marmara Pharmaceutcal Journal, 2(14), 61-66.
Yoshida, M., Takayanagi, Y., Inoue, K., Kimura, T., Young, L. J., Onaka, T., & Nishimori, K. (2009). Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci, 29(7), 2259-2271.
Yuen, K. W., Garner, J. P., Carson, D. S., Keller, J., Lembke, A., Hyde, S. A., . . . Parker, K. J. (2014). Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol. J Psychiatr Res, 51(0), 30-36.
Zhang, H., Wu, C., Chen, Q., Chen, X., Xu, Z., Wu, J., & Cai, D. (2013). Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models. PLoS One, 8(5), e61477.
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