催产素在孤独症谱系障碍患者核心症状中的作用及机制
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摘要
孤独症谱系障碍(ASD)是一种严重的神经发育性疾病,尚无明确的致病机制及治愈方法。近年来,ASD发病率呈现迅速上升趋势,引起了研究者的广泛关注。国内外大量研究显示,催产素(OT)在缓解ASD患者核心症状方面发挥着重要作用。OT是一种由9个氨基酸构成的多肽,主要由哺乳动物下丘脑的室旁核和视上核巨大神经细胞合成,并通过垂体后叶的轴突末梢释放到血液中。本研究全面系统地对OT治疗ASD患者社交障碍、重复刻板行为的研究进展进行回顾,并探究潜在的治疗机制,为ASD的研究和治疗提供新的思路与方向。
Autism spectrum disorder(ASD) is a kind of neurodevelopmental disease with uncertain mechanisms and treatments. With the prevalence of ASD been rising rapidly, researchers pay much attention to this special group. Numerous studies have shown that oxytocin(OT) might play an important role in relieving core symptoms of individuals with ASD. OT is a nonapeptide mainly synthesized in the paraventricular and supraoptic nucleus of the hypothalamus. It is released into the bloodstream in posterior pituitary. In this review, we will make a more comprehensive review of the efficacy of OT in core symptoms, and explore the potential mechanisms, providing a new idea and direction for the future research and ASD therapy.
Autism spectrum disorder(ASD) is a kind of neurodevelopmental disease with uncertain mechanisms and treatments. With the prevalence of ASD been rising rapidly, researchers pay much attention to this special group. Numerous studies have shown that oxytocin(OT) might play an important role in relieving core symptoms of individuals with ASD. OT is a nonapeptide mainly synthesized in the paraventricular and supraoptic nucleus of the hypothalamus. It is released into the bloodstream in posterior pituitary. In this review, we will make a more comprehensive review of the efficacy of OT in core symptoms, and explore the potential mechanisms, providing a new idea and direction for the future research and ASD therapy.
引文
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2 Baio J,Wiggins L,Christensen DL,et al.Prevalence of Autism Spectrum Disorder Among Children Aged 8 YearsAutism and Developmental Disabilities Monitoring Network,11 Sites,United States,2014.MMWR SURVEILLANCESUMMARIES,2018,67(6):1-23
3 Chaste P,Leboyer M.Autism risk factors:genes,environment,and gene-environment interactions.Dialogues in Clinical Neuroscience,2012,14(3):281
4陈婧,肖翠萍.机器人技术在自闭症儿童干预中的应用.中国临床心理学杂志,2017,25(4):789-792
5徐云,张宇慧.家庭亲密度和适应性、子女教育心理控制源与自闭症儿童问题行为的关系.中国临床心理学杂志,2018,26(1):78-81
6杨昱,王曼.学龄前孤独症儿童家庭的职业和经济负担调查.中国临床心理学杂志,2014,22(2):295-297
7 Kosfeld M,Heinrichs M,Zak PJ,et al.Oxytocin increases trust in humans.Nature,2005,435(7042):673-676
8 Waller C,Wittfoth M,Fritzsche K,et al.Attachment representation modulates oxytocin effects on the processing of own-child faces in fathers.Psychoneuroendocrinology,2015,62(1):27-35
9 Hollander E,Novotny S,Hanratty M,et al.Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger’s Disorders.Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology,2003,28(1):193-198
10 Lancel M,Kr?mer S,Neumann ID.Intracerebral oxytocin modulates sleep-wake behaviour in male rats.Regul Pept,2003,114(2):145-152
11 Sabihi S,Dong SM,Maurer SD,et al.Oxytocin in the medial prefrontal cortex attenuates anxiety:Anatomical and receptor specificity and mechanism of action.Neuropharmacology,2017,125(1):1-12
12刘超斌,王梅英,李东舫.催产素的研究进展.中华妇产科杂志,1999,34(5):312-314
13尚思源,苏彦捷.催产素系统与社会行为--催产素及其受体基因的作用机制.心理技术与应用,2016,4(4):224-235
14颜林,袁瑞.侧脑室内注射催产素大鼠对热和压力所致疼痛的敏感性变化.山东医药,2018,58(4):39-41
15 Caldwell HK,Aulino EA,Freeman AR,et al.Oxytocin and behavior:Lessons from knockout mice.Developmental Neurobiology,2016,77(2):190
16 Blitzer DS,Wells TE,Hawley WR.Administration of an oxytocin receptor antagonist attenuates sexual motivation in male rats.Hormones&Behavior,2017,94(1):33-39
17 Winslow JT,Insel TR.The social deficits of the oxytocin knockout mouse.Neuropeptides,2002,36(2-3):221-229
18 Pe?agarikano O,Lázaro MT,Lu XH,et al.Exogenous and evoked oxytocin restores social behavior in the Cntnap 2mouse model of autism.Science Translational Medicine,2015,7(271):218-271
19 Ferguson JN,Young LJ,Hearn EF,et al.Social amnesia in mice lacking the oxytocin gene.Nature Genetics,2000,25(3):284
20 Guastella AJ,Mitchell PB,Dadds MR.Oxytocin Increases Gaze to the Eye Region of Human Faces.Biological Psychiatry,2008,63(1):3-5
21 Leppanen J,Ng KW,Tchanturia K,et al.Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.Neuroscience&Biobehavioral Reviews,2017,78(1):125
22 Domes G,Lischke A,Berger C,et al.Effects of intranasal oxytocin on emotional face processing in women.Psychoneuroendocrinology,2010,35(1):83-93
23 Radke S,Volman I,Kokal I,et al.Oxytocin reduces amygdala responses during threat approach.Psychoneuroendocrinology,2017,79(1):160
24 Sanathara N M,Garau C,Alachkar A,et al.Melanin concentrating hormone modulates oxytocin-mediated marble burying.Neuropharmacology,2017,128(1):22-32
25 Pobbe RLH,Pearson BL,Defensor EB,et al.Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors.Hormones&Behavior,2012,61(3):436-444
26 Teng BL,Nonneman RJ,Agster KL,et al.Prosocial effects of oxytocin in two mouse models of autism spectrum disorders.Neuropharmacology,2013,72(3):187-196
27 Yang CJ,Tan HP,Yang FY,et al.The cortisol,serotonin and oxytocin are associated with repetitive behavior in autism spectrum disorder.Research in Autism Spectrum Disorders,2015,18(1):12-20
28郑培榆,邵智,张雅如,等.孤独症患儿血清催产素水平与社交能力关系的研究.重庆医学,2017,46(14):1922-1923
29 Senju A,Johnson MH.Atypical eye contact in autism:models,mechanisms and development.Neuroscience&Biobehavioral Reviews,2009,33(8):1204-1214
30 Weigelt S,Koldewyn K,Kanwisher N.Face identity recognition in autism spectrum disorders:a review of behavioral studies.Neuroscience&Biobehavioral Reviews,2012,36(3):1060-1084
31 Berggren S,Fletcherwatson S,Milenkovic N,et al.Emotion recognition training in autism spectrum disorder:A systematic review of challenges related to generalizability.Developmental Neurorehabilitation,2017,21(3):1-14
32 Yang Y,Tian Y,Fang J,et al.Trust and Deception in Children with Autism Spectrum Disorders:A Social Learning Perspective.Journal of Autism&Developmental Disorders,2017,47(3):1-11
33 Andari E,Duhamel JR,Zalla T,et al.Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.Proceedings of the National Academy of Sciences of the United States of America,2010,107(9):4389-4394
34 Auyeung B,Lombardo MV,Heinrichs M,et al.Oxytocin increases eye contact during a real-time,naturalistic social interaction in males with and without autism.Translational Psychiatry,2015,5(3):e507
35 Andari E,Richard N,Leboyer M,et al.Adaptive coding of the value of social cues with oxytocin,an fMRI study in autism spectrum disorder.Cortex,2016,76(1):79-88
36 Kanat M,Spenthof I,Riedel A,et al.Restoring effects of oxytocin on the attentional preference for faces in autism.Translational Psychiatry,2017,7(4):e1097
37 Globerson E,Amir N,Kishonrabin L,et al.Prosody recognition in adults with high-functioning autism spectrum disorders:from psychoacoustics to cognition.Autism Research,2015,8(2):153-163
38 Wingenbach TSH,Ashwin C,Brosnan M.Diminished sensitivity and specificity at recognising facial emotional expressions of varying intensity underlie emotion-specific recognition deficits in autism spectrum disorders.Research in Autism Spectrum Disorders,2017,34(1):52-61
39 Hollander E,Bartz J,Chaplin W,et al.Oxytocin increases retention of social cognition in autism.Biological Psychiatry,2007,61(4):498-503
40 Domes G,Kumbier E,Heinrichs M,et al.Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome.Neuropsychopharmacology,2014,39(3):698-706
41 Xu L,Ma X,Zhao W,et al.Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.Psychoneuroendocrinology,2015,62(1):352-358
42 Yamasue H,Okada T,Munesue T,et al.Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder:a randomized clinical trial.Molecular Psychiatry,2018,23(8):1-10
43 Parker KJ,Oztan O,Libove RA,et al.Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.Proceedings of the National Academy of Sciences of the United States of America,2017,114(30):8119
44闫喜春,程怡,杨长江.催产素对孤独症谱系障碍患者的影响:随机对照试验的系统综述和meta分析.中国临床心理学杂志,2018,26(2):327-332
45 Norman GJ,Hawkley L,Luhmann M,et al.Variation in the oxytocin receptor gene influences neurocardiac reactivity to social stress and HPA function:A population based study.Hormones&Behavior,2011,61(1):134-139
46 Rault JL,Carter CS,Garner JP,et al.Repeated intranasal oxytocin administration in early life dysregulates the HPAaxis and alters social behavior.Physiology&Behavior,2013,112(4):40-48
47 Weisman O,Zagoory-Sharon O,Feldman R.Oxytocin administration alters HPA reactivity in the context of parentinfant interaction.European Neuropsychopharmacology,2013,23(12):1724-1731
48 Bauman M,Kemper T L.Histoanatomic observations of the brain in early infantile autism.Neurology,1985,35(6):866-874
49 Top JD,Stephenson KG,Doxey CR,et al.Atypical Amygdala Response to Fear Conditioning in Autism Spectrum Disorder.Biological Psychiatry Cognitive Neuroscience&Neuroimaging,2016,1(4):308
50 Neumann ID.Stimuli and consequences of dendritic release of oxytocin within the brain.Biochemical Society Transactions,2007,35(5):1252-1257
51 Greene RK,Spanos M,Alderman C,et al.The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.Journal of Neurodevelopmental Disorders,2018,10(1):12
52 Aoki Y,Yahata N,Watanabe T,et al.Oxytocin improves behavioural and neural deficits in inferring others’social emotions in autism.Brain A Journal of Neurology,2014,137(11):3073-3086
53 Adamantidis A,Lecea LD.A role for Melanin-Concentrating Hormone in learning and memory.Peptides,2009,30(11):2066-2070
54 Jgp F,Bittencourt JC,Adamantidis A.Melanin-concentrating hormone and sleep.Current Opinion in Neurobiology,2017,44(3):152-158
55 Hollander E,Anagnostou E,Chaplin W,et al.Striatal Volume on Magnetic Resonance Imaging and Repetitive Behaviors in Autism.Biological Psychiatry,2005,58(3):226-232
56 Traynor JM,Doylethomas K,Hanford LC,et al.Indices of repetitive behaviour are correlated with patterns of intrinsic functional connectivity in youth with autism spectrum disorder.Brain Research,2018,1685(8):79-90
2 Baio J,Wiggins L,Christensen DL,et al.Prevalence of Autism Spectrum Disorder Among Children Aged 8 YearsAutism and Developmental Disabilities Monitoring Network,11 Sites,United States,2014.MMWR SURVEILLANCESUMMARIES,2018,67(6):1-23
3 Chaste P,Leboyer M.Autism risk factors:genes,environment,and gene-environment interactions.Dialogues in Clinical Neuroscience,2012,14(3):281
4陈婧,肖翠萍.机器人技术在自闭症儿童干预中的应用.中国临床心理学杂志,2017,25(4):789-792
5徐云,张宇慧.家庭亲密度和适应性、子女教育心理控制源与自闭症儿童问题行为的关系.中国临床心理学杂志,2018,26(1):78-81
6杨昱,王曼.学龄前孤独症儿童家庭的职业和经济负担调查.中国临床心理学杂志,2014,22(2):295-297
7 Kosfeld M,Heinrichs M,Zak PJ,et al.Oxytocin increases trust in humans.Nature,2005,435(7042):673-676
8 Waller C,Wittfoth M,Fritzsche K,et al.Attachment representation modulates oxytocin effects on the processing of own-child faces in fathers.Psychoneuroendocrinology,2015,62(1):27-35
9 Hollander E,Novotny S,Hanratty M,et al.Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger’s Disorders.Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology,2003,28(1):193-198
10 Lancel M,Kr?mer S,Neumann ID.Intracerebral oxytocin modulates sleep-wake behaviour in male rats.Regul Pept,2003,114(2):145-152
11 Sabihi S,Dong SM,Maurer SD,et al.Oxytocin in the medial prefrontal cortex attenuates anxiety:Anatomical and receptor specificity and mechanism of action.Neuropharmacology,2017,125(1):1-12
12刘超斌,王梅英,李东舫.催产素的研究进展.中华妇产科杂志,1999,34(5):312-314
13尚思源,苏彦捷.催产素系统与社会行为--催产素及其受体基因的作用机制.心理技术与应用,2016,4(4):224-235
14颜林,袁瑞.侧脑室内注射催产素大鼠对热和压力所致疼痛的敏感性变化.山东医药,2018,58(4):39-41
15 Caldwell HK,Aulino EA,Freeman AR,et al.Oxytocin and behavior:Lessons from knockout mice.Developmental Neurobiology,2016,77(2):190
16 Blitzer DS,Wells TE,Hawley WR.Administration of an oxytocin receptor antagonist attenuates sexual motivation in male rats.Hormones&Behavior,2017,94(1):33-39
17 Winslow JT,Insel TR.The social deficits of the oxytocin knockout mouse.Neuropeptides,2002,36(2-3):221-229
18 Pe?agarikano O,Lázaro MT,Lu XH,et al.Exogenous and evoked oxytocin restores social behavior in the Cntnap 2mouse model of autism.Science Translational Medicine,2015,7(271):218-271
19 Ferguson JN,Young LJ,Hearn EF,et al.Social amnesia in mice lacking the oxytocin gene.Nature Genetics,2000,25(3):284
20 Guastella AJ,Mitchell PB,Dadds MR.Oxytocin Increases Gaze to the Eye Region of Human Faces.Biological Psychiatry,2008,63(1):3-5
21 Leppanen J,Ng KW,Tchanturia K,et al.Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.Neuroscience&Biobehavioral Reviews,2017,78(1):125
22 Domes G,Lischke A,Berger C,et al.Effects of intranasal oxytocin on emotional face processing in women.Psychoneuroendocrinology,2010,35(1):83-93
23 Radke S,Volman I,Kokal I,et al.Oxytocin reduces amygdala responses during threat approach.Psychoneuroendocrinology,2017,79(1):160
24 Sanathara N M,Garau C,Alachkar A,et al.Melanin concentrating hormone modulates oxytocin-mediated marble burying.Neuropharmacology,2017,128(1):22-32
25 Pobbe RLH,Pearson BL,Defensor EB,et al.Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors.Hormones&Behavior,2012,61(3):436-444
26 Teng BL,Nonneman RJ,Agster KL,et al.Prosocial effects of oxytocin in two mouse models of autism spectrum disorders.Neuropharmacology,2013,72(3):187-196
27 Yang CJ,Tan HP,Yang FY,et al.The cortisol,serotonin and oxytocin are associated with repetitive behavior in autism spectrum disorder.Research in Autism Spectrum Disorders,2015,18(1):12-20
28郑培榆,邵智,张雅如,等.孤独症患儿血清催产素水平与社交能力关系的研究.重庆医学,2017,46(14):1922-1923
29 Senju A,Johnson MH.Atypical eye contact in autism:models,mechanisms and development.Neuroscience&Biobehavioral Reviews,2009,33(8):1204-1214
30 Weigelt S,Koldewyn K,Kanwisher N.Face identity recognition in autism spectrum disorders:a review of behavioral studies.Neuroscience&Biobehavioral Reviews,2012,36(3):1060-1084
31 Berggren S,Fletcherwatson S,Milenkovic N,et al.Emotion recognition training in autism spectrum disorder:A systematic review of challenges related to generalizability.Developmental Neurorehabilitation,2017,21(3):1-14
32 Yang Y,Tian Y,Fang J,et al.Trust and Deception in Children with Autism Spectrum Disorders:A Social Learning Perspective.Journal of Autism&Developmental Disorders,2017,47(3):1-11
33 Andari E,Duhamel JR,Zalla T,et al.Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.Proceedings of the National Academy of Sciences of the United States of America,2010,107(9):4389-4394
34 Auyeung B,Lombardo MV,Heinrichs M,et al.Oxytocin increases eye contact during a real-time,naturalistic social interaction in males with and without autism.Translational Psychiatry,2015,5(3):e507
35 Andari E,Richard N,Leboyer M,et al.Adaptive coding of the value of social cues with oxytocin,an fMRI study in autism spectrum disorder.Cortex,2016,76(1):79-88
36 Kanat M,Spenthof I,Riedel A,et al.Restoring effects of oxytocin on the attentional preference for faces in autism.Translational Psychiatry,2017,7(4):e1097
37 Globerson E,Amir N,Kishonrabin L,et al.Prosody recognition in adults with high-functioning autism spectrum disorders:from psychoacoustics to cognition.Autism Research,2015,8(2):153-163
38 Wingenbach TSH,Ashwin C,Brosnan M.Diminished sensitivity and specificity at recognising facial emotional expressions of varying intensity underlie emotion-specific recognition deficits in autism spectrum disorders.Research in Autism Spectrum Disorders,2017,34(1):52-61
39 Hollander E,Bartz J,Chaplin W,et al.Oxytocin increases retention of social cognition in autism.Biological Psychiatry,2007,61(4):498-503
40 Domes G,Kumbier E,Heinrichs M,et al.Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome.Neuropsychopharmacology,2014,39(3):698-706
41 Xu L,Ma X,Zhao W,et al.Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.Psychoneuroendocrinology,2015,62(1):352-358
42 Yamasue H,Okada T,Munesue T,et al.Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder:a randomized clinical trial.Molecular Psychiatry,2018,23(8):1-10
43 Parker KJ,Oztan O,Libove RA,et al.Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism.Proceedings of the National Academy of Sciences of the United States of America,2017,114(30):8119
44闫喜春,程怡,杨长江.催产素对孤独症谱系障碍患者的影响:随机对照试验的系统综述和meta分析.中国临床心理学杂志,2018,26(2):327-332
45 Norman GJ,Hawkley L,Luhmann M,et al.Variation in the oxytocin receptor gene influences neurocardiac reactivity to social stress and HPA function:A population based study.Hormones&Behavior,2011,61(1):134-139
46 Rault JL,Carter CS,Garner JP,et al.Repeated intranasal oxytocin administration in early life dysregulates the HPAaxis and alters social behavior.Physiology&Behavior,2013,112(4):40-48
47 Weisman O,Zagoory-Sharon O,Feldman R.Oxytocin administration alters HPA reactivity in the context of parentinfant interaction.European Neuropsychopharmacology,2013,23(12):1724-1731
48 Bauman M,Kemper T L.Histoanatomic observations of the brain in early infantile autism.Neurology,1985,35(6):866-874
49 Top JD,Stephenson KG,Doxey CR,et al.Atypical Amygdala Response to Fear Conditioning in Autism Spectrum Disorder.Biological Psychiatry Cognitive Neuroscience&Neuroimaging,2016,1(4):308
50 Neumann ID.Stimuli and consequences of dendritic release of oxytocin within the brain.Biochemical Society Transactions,2007,35(5):1252-1257
51 Greene RK,Spanos M,Alderman C,et al.The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.Journal of Neurodevelopmental Disorders,2018,10(1):12
52 Aoki Y,Yahata N,Watanabe T,et al.Oxytocin improves behavioural and neural deficits in inferring others’social emotions in autism.Brain A Journal of Neurology,2014,137(11):3073-3086
53 Adamantidis A,Lecea LD.A role for Melanin-Concentrating Hormone in learning and memory.Peptides,2009,30(11):2066-2070
54 Jgp F,Bittencourt JC,Adamantidis A.Melanin-concentrating hormone and sleep.Current Opinion in Neurobiology,2017,44(3):152-158
55 Hollander E,Anagnostou E,Chaplin W,et al.Striatal Volume on Magnetic Resonance Imaging and Repetitive Behaviors in Autism.Biological Psychiatry,2005,58(3):226-232
56 Traynor JM,Doylethomas K,Hanford LC,et al.Indices of repetitive behaviour are correlated with patterns of intrinsic functional connectivity in youth with autism spectrum disorder.Brain Research,2018,1685(8):79-90