The Role of Intranasal Oxytocin in Anxiety and Depressive Disorders: A Systematic Review of Randomized Controlled Trials

다국어 초록 (Multilingual Abstract)

Several studies have demonstrated the neuromodulating function of oxytocin (OT) in response to anxiogenic stimuli as well as its potential role in the pathogenesis of depression. Consequently, intranasal OT (IN-OT) has been proposed as a potential treatment of anxiety and depressive disorders. The present systematic review aimed to summarize the randomized controlled trials (RCTs) evaluating the effect of IN-OT on anxiety and depressive symptoms. Overall, 15 studies were included, involving patients with social anxiety disorders (7 studies), arachnophobia (1), major depression (3) or post-natal depression (4), and mainly evaluating single-dose administrations of IN-OT. Results showed no significant effects on core symptomatology. Five crossover studies included functional magnetic resonance imaging investigation: one trial showed reduced amygdala hyper-reactivity after IN-OT in subjects with anxiety, while another one showed enhanced connectivity between amygdala and bilateral insula and middle cingulate gyrus after IN-OT in patients but not in healthy controls. More studies are needed to confirm these results. In conclusion, up to date, evidence regarding the potential utility of IN-OT in treating anxiety and depression is still inconclusive. Further RCTs with larger samples and long-term administration of IN-OT are needed to better elucidate its potential efficacy alone or in association with standard care.

참고문헌 (Reference)

1 Nyuyki KD, "Yes, I am ready now : differential effects of paced versus unpaced mating on anxiety and central oxytocin release in female rats" 6 : e23599-, 2011

2 Treadway MT, "Worth the ‘EEfRT’? The effort expenditure for rewards task as an objective measure of motivation and anhedonia" 4 : e6598-, 2009

3 Fang A, "Working hard for oneself or others : Effects of oxytocin on reward motivation in social anxiety disorder" 127 : 157-162, 2017

4 Bond A, "The use of analogue scales in rating subjective feelings" 47 : 211-218, 1974

5 Shin LM, "The neurocircuitry of fear, stress, and anxiety disorders" 35 : 169-191, 2010

6 Mah BL, "The effects of intranasal oxytocin administration on sensitive caregiving in mothers with postnatal depression" 48 : 308-315, 2017

7 Domes G, "The effect of oxytocin on attention to angry and happy faces in chronic depression" 16 : 92-, 2016

8 Alessandro Serretti, "The Present and Future of Precision Medicine in Psychiatry: Focus on Clinical Psychopharmacology of Antidepressants" 대한정신약물학회 16 (16): 1-6, 2018

9 Higgins JPT, "The Cochrane collaboration’s tool for assessing risk of bias in randomised trials" 343 : d5928-, 2011

10 Brondino N, "Something to talk about : gossip increases oxytocin levels in a near real-life situation" 77 : 218-224, 2017

11 Liebowitz MR, "Social phobia" 22 : 141-173, 1987

12 Spielberg CD, "STAI manual for the State-Trait Anxiety Inventory" Consulting Psychologists Press 1970

13 Turner SM, "SPAI Manual" Multi-Health Systems 1996

14 Klorman R, "Psychometric description of some specific-fear questionnaires" 5 : 401-409, 1974

15 Moher D, "Preferred reporting items for systematic reviews and meta-analyses : the PRISMA Statement" 3 : e123-, 2009

16 Rutigliano G, "Peripheral oxytocin and vasopressin : Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis" 241 : 207-220, 2016

17 Hashimoto H, "Pathophysiological function of oxytocin secreted by neuropeptides : a mini review" 19 : 283-298, 2012

18 Bartz JA, "Oxytocin selectively improves empathic accuracy" 21 : 1426-1428, 2010

19 Mah BL, "Oxytocin promotes protective behavior in depressed mothers : a pilot study with the enthusiastic stranger paradigm" 32 : 76-81, 2015

20 Gorka SM, "Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder" 40 : 278-286, 2015

21 Mah BL, "Oxytocin in postnatally depressed mothers : its influence on mood and expressed emotion" 40 : 267-272, 2013

22 Neumann ID, "Oxytocin in general anxiety and social fear : a translational approach" 79 : 213-221, 2016

23 Domes G, "Oxytocin improves"mind-reading"in humans" 61 : 731-733, 2007

24 Feeser M, "Oxytocin improves mentalizing-pronounced effects for individuals with attenuated ability to empathize" 53 : 223-232, 2015

25 Sripada CS, "Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex" 16 : 255-260, 2013

26 Di Simplicio M, "Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers" 23 : 241-248, 2009

27 Levine A, "Oxytocin during pregnancy and early postpartum : individual patterns and maternal-fetal attachment" 28 : 1162-1169, 2007

28 Labuschagne I, "Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder" 35 : 2403-2413, 2010

29 MacDonald K, "Oxytocin and psychotherapy : a pilot study of its physiological, behavioral and subjective effects in males with depression" 38 : 2831-2843, 2013

30 Matsuzaki M, "Oxytocin : a therapeutic target for mental disorders" 62 : 441-444, 2012

31 Posner MI, "Orienting of attention" 32 : 3-25, 1980

32 Slattery DA, "No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain" 586 : 377-385, 2008

33 Stoop R, "Neuromodulation by oxytocin and vasopressin" 76 : 142-159, 2012

34 Rocchetti M, "Neurofunctional maps of the 'maternal brain' and the effects of oxytocin : a multimodal voxel-based meta-analysis" 68 : 733-751, 2014

35 Dodhia S, "Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder" 39 : 2061-2069, 2014

36 Churchland PS, "Modulating social behavior with oxytocin : how does it work? What does it mean" 61 : 392-399, 2012

37 Rapee RM, "Mental representation of observable attributes in people with social phobia" 37 : 113-126, 2006

38 Labuschagne I, "Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin" 15 : 883-896, 2012

39 McNair DM, "Manual for the profile of mood states" Educational and Industrial Testing Service 1971

40 McQuaid RJ, "Making room for oxytocin in understanding depression" 45 : 305-322, 2014

41 Pincus D, "Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects : a double-blind placebo controlled FMRI study" 1 : 134-, 2010

42 Pedersen CA, "Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia" 132 : 50-53, 2011

43 Guastella AJ, "Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders" 67 : 692-694, 2010

44 Lischke A, "Intranasal oxytocin enhances emotion recognition from dynamic facial expressions and leaves eye-gaze unaffected" 37 : 475-481, 2012

45 Acheson DT, "Intranasal oxytocin administration prior to exposure therapy for arachnophobia impedes treatment response" 32 : 400-407, 2015

46 Clarici A, "Intranasal adminsitration of oxytocin in postnatal depression : implications for psychodynamic psychotherapy from a randomized double-blind pilot study" 6 : 426-, 2015

47 Bell AF, "Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy" 6 : 243-, 2015

48 Stein MB, "Increased amygdala and insula activation during emotion processing in anxiety-prone subjects" 164 : 318-327, 2007

49 Szymanski J, "Fear of Spiders Questionnaire" 26 : 31-34, 1995

50 Feldman R, "Evidence for a neuroendocrinological foundation of human affiliation : plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding" 18 : 965-970, 2007

51 Williams DR, "Effects of intranasal oxytocin on symptoms of schizophrenia : A multivariate Bayesian metaanalysis" 75 : 141-151, 2017

52 Guy W, "ECDEU assessment manual for psychopharmacology" US Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration 1976

53 Baskerville TA, "Dopamine and oxytocin interactions underlying behaviors : potential contributions to behavioral disorders" 16 : e92-, 2010

54 Radke S, "Does oxytocin affect mind-reading? A replication study" 60 : 75-81, 2015

55 Rapee RM, "Discrepancy between self-and observer ratings of performance in social phobics" 101 : 728-731, 1992

56 American Psychiatric Association, "Diagnostic and statistical manual of mental disorders" APA Press 2013

57 Hamilton M, "Development of a rating scale for primary depressive illness" 6 : 278-296, 1967

58 Watson D, "Development and validation of brief measures of positive and negative affect : the PANAS scales" 54 : 1063-1070, 1988

59 Cox JL, "Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale" 150 : 782-786, 1987

60 Williams KD, "Cyberostracism : effects of being ignored over the Internet" 79 : 748-762, 2000

61 Williams KD, "Cyberball : a program for use in research on interpersonal ostracism and acceptance" 38 : 174-180, 2006

62 Waldherr M, "Centrally released oxytocin mediates mating-induced anxiolysis in male rats" 104 : 16681-16684, 2007

63 Neumann ID, "Balance of brain oxytocin and vasopressin : implications for anxiety, depression, and social behaviors" 35 : 649-659, 2012

64 Posner MI, "Attention and the detection of signals" 109 : 160-174, 1980

65 Fang A, "Attachment style moderates the effects of oxytocin on social behaviors and cognitions during social rejection : applying an RDoC framework to social anxiety" 2 : 740-747, 2014

66 Kroll-Desrosiers AR, "Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year" 34 : 137-146, 2017

67 Stuebe AM, "Association between maternal mood and oxytocin response to breastfeeding" 22 : 352-361, 2013

68 Mochcovitch MD, "A systematic review of fMRI studies in generalized anxiety disorder : Evaluating its neural and cognitive basis" 167 : 336-342, 2014

69 MacDonald E, "A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research" 36 : 1114-1126, 2011

70 Guastella AJ, "A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder" 34 : 917-923, 2009

71 Mark RL, "A brief version of the fear of negative evaluation scale" 9 : 371-375, 1983