Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities

Sippel, Lauren M.; Allington, Casey E.; Pietrzak, Robert H.; Harpaz-Rotem, Ilan; Mayes, Linda C.; Olff, Miranda

doi:10.1177/2470547016687996

Cited by 99Neuroendocrine regulation and behaviorStress Responses and CortisolNeuropeptides and Animal Physiology

Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities

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Sippel, Lauren M., Allington, Casey E., Pietrzak, Robert H., Harpaz-Rotem, Ilan, Mayes, Linda C., Olff, Miranda·2017·Chronic Stress

DOI 10.1177/2470547016687996PMC PMC5482285

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Abstract

Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social–emotional brain. In this review, we present an overview of evidence supporting OT’s utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e.g., the salience network and hypothalamic–pituitary–adrenal axis). Third, we present the sparse but promising findings from clinical populations, followed by discussion of critical moderating variables to consider in the service of maximizing the therapeutic potential of OT (e.g., patient sex and child maltreatment). We also identify heterogeneous findings and limitations of existing research, including reliance on single-dose studies in psychiatrically healthy samples and unanswered questions regarding the effectiveness of IN drug delivery and dosing schedules. Well-controlled multidose studies including women and measures of potentially moderating variables are sorely needed and would inform our understanding of the utility of OT for preventing and treating stress-related psychiatric disorders.

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OXT influences processes implicated in disorders characterized by social deficits, such as major depressive disorder, posttraumatic stress disorder, ADS, and schizophrenia.
“Studies indicate that OXT influences processes implicated in disorders characterized by social deficits, such as major depressive disorder, posttraumatic stress disorder, ADS, and schizophrenia (Cochran et al., 2013; Sippel et al., 2017).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Sippel et al., 2017
The Introduction (page unavailable) identifies altered social behavior in PTSD and major depressive disorder, and the Oxytocin section describes effects on social cognition and reward processing. The copy discusses autistic traits, but not the printed term “ADS” as a diagnosis; schizophrenia appears in a cited study’s title rather than in a discussion establishing the claim for that disorder. Thus, the four-disorder list is broader than this source supports. (LLM, conf=0.86)
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Social facilitation of wound healing
Detillion, C. E., Craft, T. K. S., Glasper, E. R., Prendergast, B. J., & DeVries, A. C. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2003.10.003 · Cited by 259 · see citing works
Reward functioning in PTSD: a systematic review exploring the mechanisms underlying anhedonia
Nawijn, L., van Zuiden, M., Frijling, J. L., Koch, S. B. J., Veltman, D. J., & Olff, M. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.01.019 · Cited by 250 · see citing works
Self-citation
Salivary oxytocin concentrations in response to running, sexual self-stimulation, breastfeeding and the TSST: The Regensburg Oxytocin Challenge (ROC) study
Jong, T. R. D., Menon, R., Bludau, A., Grund, T., Biermeier, V., Klampfl, S. M., Jurek, B., Bosch, O. J., Hellhammer, J., & Neumann, I. D. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.08.027 · Cited by 250 · see citing works
The human oxytocin gene promoter is regulated by estrogens
Richard, S., & Zingg, H. H. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39297-x · Cited by 242 · see citing works
Oxytocin facilitates protective responses to aversive social stimuli in males
Striepens, N., Scheele, D., Kendrick, K. M., Becker, B., Schäfer, L., Schwalba, K., Reul, J., Maier, W., & Hurlemann, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208852109 · Cited by 242 · see citing works
Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers
Leng, G., & Sabatier, N. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12413 · Cited by 237 · cited 1× · see citing works
“For example, there are large discrepancies in OT levels measured from unextracted and extracted plasma.(43) Values derived from unextracted samples have been found to be two orders of magnitude higher, likely because molecules besides OT are tagged and detected.”
Background
Effects of oxytocin on recollections of maternal care and closeness
Bartz, J. A., Zaki, J., Ochsner, K. N., Bolger, N., Kolevzon, A., Ludwig, N., & Lydon, J. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012669107 · Cited by 235 · cited 1× · see citing works
“Similarly, anxiously attached individuals remembered their mothers as less caring and close following OT versus placebo, compared with securely attached individuals, who remembered their mothers as more caring and close in childhood following IN OT versus placebo.(170) Alternatively, some studies suggest utility of IN…”
Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers
Di Simplicio, M., Massey-Chase, R., Cowen, P., & Harmer, C. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108095705 · Cited by 229 · see citing works
The Role of Oxytocin in Human Affect: A Novel Hypothesis
Kemp, A. H., & Guastella, A. J. (2011) · Current Directions in Psychological Science · doi:10.1177/0963721411417547 · Cited by 228 · see citing works
Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain.
Groppe, S. E., Gossen, A., Rademacher, L., Hahn, A., Westphal, L., Gründer, G., & Spreckelmeyer, K. N. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.023 · Cited by 218 · see citing works
Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: Moderation by oxytocin receptor gene
Bradley, B., Westen, D., Mercer, K. B., Binder, E. B., Jovanovic, T., Crain, D., Wingo, A., & Heim, C. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000162 · Cited by 213 · see citing works
Oxytocin facilitates the extinction of conditioned fear in humans
Eckstein, M., Becker, B., Scheele, D., Scholz, C., Preckel, K., Schlaepfer, T. E., Grinevich, V., Kendrick, K. M., Maier, W., & Hurlemann, R. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.10.015 · Cited by 210 · see citing works
Sensitivity to Intranasal Oxytocin in Adult Men with Early Parental Separation
Meinlschmidt, G., & Heim, C. C. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.007 · Cited by 210 · see citing works
Oxytocin receptor genetic variation promotes human trust behavior
Krueger, F., Parasuraman, R., Iyengar, V., Thornburg, M., Weel, J., Lin, M., Clarke, E., McCabe, K., & Lipsky, R. H. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00004 · Cited by 207 · see citing works
The psychobiology of PTSD: Coping with trauma
Olff, M., Langeland, W., & Gersons, B. P. R. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.04.009 · Cited by 207 · see citing works
Self-citation
Oxytocin buffers cortisol responses to stress in individuals with impaired emotion regulation abilities
Quirin, M., Kuhl, J., & Düsing, R. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.12.005 · Cited by 204 · see citing works
Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex
Sripada, C. S., Phan, K. L., Labuschagne, I., Welsh, R., Nathan, P. J., & Wood, A. G. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000533 · Cited by 197 · see citing works
Oxytocin increases amygdala reactivity to threatening scenes in females
Lischke, A., Gamer, M., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., Herpertz, S. C., & Domes, G. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.01.011 · Cited by 194 · see citing works
Oxytocin increases anxiety to unpredictable threat
Grillon, C., Krimsky, M., Charney, D. R., Vytal, K., Ernst, M., & Cornwell, B. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.156 · Cited by 192 · cited 1× · see citing works
“Additional studies of the effects of IN OT on threat perception in PTSD samples are needed, given its role in the development and maintenance of PTSD,(144) OT-related increases in salience processing,(94) and evidence that IN OT increases anxiety to unpredictable threat.(145) IN OT may also have distinct effects at di…”
Background
Intranasal oxytocin attenuates the cortisol response to physical stress: a dose-response study
Cardoso, C., Ellenbogen, M. A., Orlando, M. A., Bacon, S. L., & Joober, R. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.07.013 · Cited by 187 · see citing works
Oxytocin, the peptide that bonds the sexes also divides them
Gao, S., Becker, B., Luo, L., Geng, Y., Zhao, W., Yin, Y., Hu, J., Gao, Z., Gong, Q., Hurlemann, R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602620113 · Cited by 186 · see citing works
The effect of intranasal administration of oxytocin on fear recognition
Fischer-Shofty, M., Shamay-Tsoory, S. G., Harari, H., & Levkovitz, Y. (2010) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2009.09.003 · Cited by 184 · see citing works
Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders
MacDonald, K., & Feifel, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00035 · Cited by 181 · see citing works
Oxytocin increases recognition of masked emotional faces
Schulze, L., Lischke, A., Greif, J., Herpertz, S. C., Heinrichs, M., & Domes, G. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.011 · Cited by 180 · see citing works
Switching brain serotonin with oxytocin
Mottolese, R., Redouté, J., Costes, N., Le Bars, D., & Sirigu, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319810111 · Cited by 179 · see citing works
Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies
Wigton, R., Radua, J., Allen, P., Averbeck, B., Meyer-Lindenberg, A., McGuire, P., Shergill, S. S., & Fusar-Poli, P. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130289 · Cited by 179 · see citing works
Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men
Clodi, M., Vila, G., Geyeregger, R., Riedl, M., Stulnig, T. M., Struck, J., Luger, T. A., & Luger, A. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90263.2008 · Cited by 176 · see citing works
Making room for oxytocin in understanding depression
McQuaid, R. J., McInnis, O. A., Abizaid, A. B., & Anisman, H. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.07.005 · Cited by 172 · see citing works
A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: Moderation by method and mental health
Cardoso, C., Kingdon, D., & Ellenbogen, M. A. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.07.014 · Cited by 171 · see citing works
An oxytocin-induced facilitation of neural and emotional responses to social touch correlates inversely with autism traits
Scheele, D., Kendrick, K. M., Khouri, C., Kretzer, E., Schläpfer, T. E., Stoffel-Wagner, B., Güntürkün, O., Maier, W., & Hurlemann, R. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.78 · Cited by 171 · see citing works
Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety
Weisman, O., Zagoory‐Sharon, O., Schneiderman, I., Gordon, I., & Feldman, R. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.08.011 · Cited by 170 · see citing works
Intranasal administration of oxytocin: behavioral and clinical effects, a review
Veening, J. G., & Olivier, B. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.012 · Cited by 169 · see citing works
Effects of appraisal and coping on the neuroendocrine response to extreme stress
Olff, M., Langeland, W., & Gersons, B. P. R. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.12.006 · Cited by 160 · see citing works
Self-citation
Anxiolytic-like effect of oxytocin in the simulated public speaking test
de Oliveira, D. C., Zuardi, A. W., Graeff, F. G., Queiroz, R. H., & Crippa, J. A. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111400642 · Cited by 154 · see citing works
HPA- and HPT-axis alterations in chronic posttraumatic stress disorder
Olff, M., Güzelcan, Y., de Vries, G.-J., Assies, J., & Gersons, B. P. R. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.09.003 · Cited by 153 · see citing works
Self-citation
Effects of intranasal vasopressin and oxytocin on physiologic responding during personal combat imagery in Vietnam veterans with posttraumatic stress disorder
Pitman, R. K., Orr, S. P., & Lasko, N. B. (1993) · Psychiatry Research · doi:10.1016/0165-1781(93)90035-f · Cited by 150 · see citing works
Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis
Rutigliano, G., Rocchetti, M., Paloyelis, Y., Gilleen, J., Sardella, A., Cappucciati, M., Palombini, E., Dell’Osso, L., Caverzasi, E., Politi, P., et al. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.04.117 · Cited by 149 · cited 1× · see citing works
“A meta-analysis of 64 studies of several psychiatric disorders, including MDD but not PTSD, showed no significant differences in peripheral OT between healthy and psychiatric groups (except in anorexia).(40) Compared with trauma-exposed controls, lower peripheral OT levels have been observed in men, but not women, wit…”
Method
Do delivery routes of intranasally administered oxytocin account for observed effects on social cognition and behavior? A two-level model
Quintana, D. S., Alvares, G. A., Hickie, I. B., & Guastella, A. J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.12.011 · Cited by 149 · see citing works
Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome
Hall, S. S., Lightbody, A. A., McCarthy, B. E., Parker, K. J., & Reiss, A. L. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.020 · Cited by 143 · see citing works
A heartfelt response: oxytocin effects on response to social stress in men and women
Kubzansky, L. D., Mendes, W. B., Appleton, A. A., Block, J., & Adler, G. K. (2012) · Biological Psychology · doi:10.1016/j.biopsycho.2012.02.010 · Cited by 142 · see citing works
The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample
Acheson, D., Feifel, D., de Wilde, S., Mckinney, R., Lohr, J., & Risbrough, V. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3099-4 · Cited by 141 · see citing works
Oxytocin and psychotherapy: a pilot study of its physiological, behavioral and subjective effects in males with depression
MacDonald, K., MacDonald, T. M., Brüne, M., Lamb, K., Wilson, M. P., Golshan, S., & Feifel, D. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.05.014 · Cited by 140 · see citing works
Oxytocin׳s role in anxiety: A critical appraisal
MacDonald, K., & Feifel, D. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.025 · Cited by 139 · see citing works
Oxytocin in postnatally depressed mothers: Its influence on mood and expressed emotion
Mah, B. L., van IJzendoorn, M. H., Smith, R., & Bakermans‐Kranenburg, M. J. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.005 · Cited by 135 · see citing works
A general approach-avoidance hypothesis of Oxytocin: Accounting for social and non-social effects of oxytocin
Harari-Dahan, O., & Bernstein, A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.007 · Cited by 135 · see citing works
A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder
Olff, M., Langeland, W., Witteveen, A., & Denys, D. (2010) · CNS Spectrums · doi:10.1017/s109285290000047x · Cited by 135 · see citing works
Self-citation
Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory
Lane, A., Luminet, O., Nave, G., & Mikolajczak, M. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12384 · Cited by 134 · see citing works
Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients
van Zuiden, M., Frijling, J. L., Nawijn, L., Koch, S. B. J., Goslings, J. C., Luitse, J. S., Biesheuvel, T. H., Honig, A., Veltman, D. J., & Olff, M. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.11.012 · Cited by 134 · see citing works
Self-citation
Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder
Koch, S. B. J., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.1 · Cited by 132 · see citing works
Self-citation
Bonding after trauma: on the role of social support and the oxytocin system in traumatic stress
Olff, M. (2012) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v3i0.18597 · Cited by 131 · see citing works
Self-citation
Oxytocin and Social Adaptation: Insights from Neuroimaging Studies of Healthy and Clinical Populations
Ma, Y., Shamay-Tsoory, S., Han, S., & Zink, C. F. (2016) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.10.009 · Cited by 131 · see citing works
Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques
Modi, M. E., Connor-Stroud, F., Landgraf, R., Young, L. J., & Parr, L. A. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.011 · Cited by 129 · see citing works
Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences
Bakermans‐Kranenburg, M. J., van IJzendoorn, M. H., Riem, M. M. E., Mattie Tops, A., & Alink, L. R. A. (2011) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsr067 · Cited by 126 · see citing works
Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: salience processing and fear inhibition processes
Koch, S. B. J., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.11.018 · Cited by 123 · see citing works
Self-citation
Intranasal administration of oxytocin increases human aggressive behavior
Ne'eman, R., Perach-Barzilay, N., Fischer-Shofty, M., Atias, A., & Shamay-Tsoory, S. G. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.01.015 · Cited by 121 · see citing works
Hormonal contraceptives suppress oxytocin-induced brain reward responses to the partner’s face
Scheele, D., Plota, J., Stoffel-Wagner, B., Maier, W., & Hurlemann, R. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsv157 · Cited by 116 · see citing works
Oxytocin indexes relational distress following interpersonal harms in women
Tabak, B. A., McCullough, M. E., Szeto, A., Mendez, A. J., & McCabe, P. M. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.07.004 · Cited by 116 · see citing works
Does oxytocin influence the early detection of angry and happy faces?
Guastella, A. J., Carson, D. S., Dadds, M. R., Mitchell, P. B., & Cox, R. E. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.09.001 · Cited by 114 · see citing works
Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion
De Dreu, C. K. W. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.10.003 · Cited by 114 · see citing works
Does the oxytocin receptor polymorphism (rs2254298) confer 'vulnerability' for psychopathology or 'differential susceptibility'? insights from evolution
Brüne, M. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-38 · Cited by 113 · see citing works
OxytocinSynthesis, Secretion, and Reproductive Functions
BURBACH, J., YOUNG, L., & RUSSELL, J. (2006) · Knobil and Neill's Physiology of Reproduction · doi:10.1016/b978-012515400-0/50063-4 · Cited by 113 · see citing works
Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia
Goldman, M. B., Gomes, A. M., Carter, C. S., & Lee, R. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2193-8 · Cited by 112 · see citing works
Oxytocin facilitates social approach behavior in women
Preckel, K., Scheele, D., Kendrick, K. M., Maier, W., & Hurlemann, R. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00191 · Cited by 111 · see citing works
Plasma oxytocin is related to lower cardiovascular and sympathetic reactivity to stress
Grewen, K., & Light, K. C. (2011) · Biological Psychology · doi:10.1016/j.biopsycho.2011.04.003 · Cited by 107 · see citing works
Social anxiety, depression, and PTSD in Vietnam veterans
Hofmann, S. G., Litz, B. T., & Weathers, F. W. (2002) · Journal of Anxiety Disorders · doi:10.1016/s0887-6185(02)00227-x · Cited by 107 · see citing works
Association of Predeployment Gaze Bias for Emotion Stimuli With Later Symptoms of PTSD and Depression in Soldiers Deployed in Iraq
Beevers, C. G., Lee, H.-J., Wells, T. T., Ellis, A. J., & Telch, M. J. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10091309 · Cited by 106 · see citing works
Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students
Linnen, A.-M., Ellenbogen, M. A., Cardoso, C., & Joober, R. (2012) · Stress · doi:10.3109/10253890.2011.631154 · Cited by 104 · see citing works
The influence of depressive symptomatology and perceived stress on plasma and salivary oxytocin before, during and after a support enhancement intervention
Holt-Lunstad, J., Birmingham, W., & Light, K. C. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.007 · Cited by 103 · see citing works
Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress
Engert, V., Koester, A. M., Riepenhausen, A., & Singer, T. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.08.029 · Cited by 103 · see citing works
Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial
Quintana, D. S., Westlye, L. T., Alnæs, D., Rustan, Ø. G., Kaufmann, T., Smerud, K. T., Mahmoud, R. A., Djupesland, P. G., & Andreassen, O. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.04.010 · Cited by 102 · see citing works
Menstrual cycle effects on psychological symptoms in women with PTSD
Nillni, Y. I., Pineles, S. L., Patton, S. C., Rouse, M. H., Sawyer, A. T., & Rasmusson, A. M. (2015) · Journal of Traumatic Stress · doi:10.1002/jts.21984 · Cited by 100 · see citing works
Early life stress modulates oxytocin effects on limbic system during acute psychosocial stress.
Grimm, S., Pestke, K., Feeser, M., Aust, S., Weigand, A., Wang, J., Wingenfeld, K., Pruessner, J., Marca, R. L., Böker, H., et al. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu020 · Cited by 100 · see citing works
Acute intranasal oxytocin improves positive self-perceptions of personality
Cardoso, C., Ellenbogen, M. A., & Linnen, A.-M. (2012) · Psychopharmacology · doi:10.1007/s00213-011-2527-6 · Cited by 98 · see citing works
Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients
Koch, S. B., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.299 · Cited by 98 · see citing works
Self-citation
When the Love Hormone Leads to Violence: Oxytocin Increases Intimate Partner Violence Inclinations Among High Trait Aggressive People
DeWall, C. N., Gillath, O., Pressman, S. D., Black, L. L., Bartz, J. A., Moskovitz, J., & Stetler, D. A. (2014) · Social Psychological and Personality Science · doi:10.1177/1948550613516876 · Cited by 96 · see citing works
Childhood maltreatment, juvenile disorders and adult post-traumatic stress disorder: a prospective investigation
Breslau, N., Koenen, K. C., Luo, Z., Agnew-Blais, J., Swanson, S., Houts, R. M., Poulton, R., & Moffitt, T. E. (2014) · Psychological Medicine · doi:10.1017/s0033291713002651 · Cited by 95 · see citing works
Oxytocin and Major Depressive Disorder: Experimental and Clinical Evidence for Links to Aetiology and Possible Treatment
Slattery, D. A., & Neumann, I. D. (2010) · Pharmaceuticals · doi:10.3390/ph3030702 · Cited by 94 · see citing works
Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal
Riem, M. M. E., van IJzendoorn, M. H., Tops, M., Boksem, M. A. S., Rombouts, S. A. R. B., & Bakermans-Kranenburg, M. J. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.01.011 · Cited by 91 · see citing works
Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects: a double-blind placebo controlled FMRI study
Pincus, D. (2010) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2010.00134 · Cited by 91 · see citing works
Gonadal Steroid Modulation of Stress-Induced Hypothalamo-Pituitary-Adrenal Activity and Anxiety Behavior: Role of Central Oxytocin
Windle, R. J., Gamble, L. E., Kershaw, Y. M., Wood, S. A., Lightman, S. L., & Ingram, C. D. (2006) · Endocrinology · doi:10.1210/en.2005-1079 · Cited by 90 · see citing works
Untitled work
Radke (2013) · doi:10.1177/0956797612472682 · Cited by 88 · see citing works
Oxytocin Facilitates Pavlovian Fear Learning in Males
Eckstein, M., Scheele, D., Patin, A., Preckel, K., Becker, B., Walter, A., Domschke, K., Grinevich, V., Maier, W., & Hurlemann, R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.245 · Cited by 87 · see citing works
Oxytocin’s effect on resting-state functional connectivity varies by age and sex
Ebner, N. C., Chen, H., Porges, E., Lin, T., Fischer, H., Feifel, D., & Cohen, R. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.03.013 · Cited by 84 · see citing works
The acute effects of intranasal oxytocin on automatic and effortful attentional shifting to emotional faces
Ellenbogen, M. A., Linnen, A., Grumet, R., Cardoso, C., & Joober, R. (2012) · Psychophysiology · doi:10.1111/j.1469-8986.2011.01278.x · Cited by 82 · see citing works
Association of Predeployment Gaze Bias for Emotion Stimuli With Later Symptoms of PTSD and Depression in Soldiers Deployed in Iraq
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Measurement
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Substance Use and Substance Use Disorders
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Social Support
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Social Support: Learning the Tap Code
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Mortality
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Anxiety
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Understanding the Religion–Physical Health Relationship
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Bipolar Disorder
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Copyright Page
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Oxytocin – a social neuropeptide. Is it important in the neurodevelopmental theory of depression?
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Association of oxytocin gene polymorphism with psychological distress, suicidal ideation and relapse in alcohol-dependent patients
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From Surviving to Thriving
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Summary and Conclusions
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Hypertension
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Suicide
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Depression
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Chronic Pain
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Preface
Levin, J. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780190088859.002.0007
Health Policy Implications
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Introduction
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Alzheimer’s Disease and Other Dementias
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Heart Disease
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Cancer
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Diet and Weight
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Dedication
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Personality Traits and Disorders
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Schizophrenia and Other Psychoses
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Coping with Stress
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Exercise
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Delinquency and Crime
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Foreword
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Physical Disability
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Cerebrovascular Disease
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Studies on Religion and Health
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Authors: Sippel, L. M., Allington, C. E., Pietrzak, R. H., Harpaz-Rotem, I., Mayes, L. C., & Olff, M.
Affiliations: United States Department of Veterans Affairs (US)
VA Connecticut Healthcare System (US)
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA
Yale University (US)
Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author: Sippel, Lauren M.
ORCID: Sippel, Lauren M.
Pietrzak, Robert H.
Mayes, Linda C.
Olff, Miranda
Venue: Chronic Stress
Publisher: SAGE Publications
Published: 2017-02
Volume: 1
ISSN: 2470-5470 (ISSN-L)
DOI: 10.1177/2470547016687996
PMC: PMC5482285
OpenAlex: W2588660371
Cited by: 99
References: 204
Citations by year: 2026: 4 · 2025: 4 · 2024: 5 · 2023: 43 · 2022: 8 · 2021: 10 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 1
FWCI: 9.79
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Chronic Stress (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion, other-oa)
Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc)
Data Archiving and Networked Services (DANS) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (VA999999)
National Center for PTSD, U.S. Department of Veterans Affairs
Topics: Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: oxytocin, stress-related psychiatric disorders, major depressive disorder, post-traumatic stress disorder, intranasal oxytocin, anhedonia, reward processing, fear and anxiety, social behavior, salience network, hypothalamic-pituitary-adrenal axis, child abuse, sex differences

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Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities

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