Die Rolle des Oxytocinsystems für die Entstehung der Depression

ZUSAMMENFASSUNG

Oxytocin erregte aufgrund seiner Rolle für das menschliche Sozialverhalten in den letzten Jahren vermehrt Aufmerksamkeit hinsichtlich der Erforschung der Ätiologie depressiver Erkrankungen. Aktuelle Forschungsergebnisse legen die Komplexität des Oxytocinsystems und sowohl pro- als auch antisoziale Effekte des Neuropeptids offen, weshalb seine Rolle für die Salienz sozialer Reize oder allgemeiner für allostatische Prozesse diskutiert wird. Diese Arbeit fasst Befunde zu den Zusammenhängen zwischen Oxytocin und belastenden Lebensereignissen sowie zwischen Oxytocin und der Verstärkung sozialer Interaktionen zusammen. Ausgehend von diesen Verknüpfungen des Oxytocinsystems mit dem körperlichen Stresssystem und dem Belohnungssystem stellt diese Arbeit einen Versuch dar, aktuelle Theorien zur Funktion von Oxytocin auf die Depression anzuwenden, um so eine Hypothese zur Rolle des Oxytocinsystems hinsichtlich des Ursprungs der biologischen und behavioralen Korrelate dieser Störung aufzustellen.

ABSTRACT

Oxytocin has attracted increased attention in recent years with regard to research on the etiology of depressive disorders due to its role in human social behavior. Recent research has revealed the complexity of the oxytocin system and both pro- as well as antisocial effects of the neuropeptide, thus its role in the salience of social stimuli or more generally in allostatic processes is debated. This paper summarizes findings on the links between oxytocin and stressful life events as well as between oxytocin and reinforcement of social interactions. Based on these linkages of the oxytocin system with the physical stress system and the reward system, this work represents an attempt to apply current theories on the oxytocin system to depression to hypothesize the role of the oxytocin system with respect to the origin of the biological and behavioral correlates of this disorder.

Schlüsselwörter

Stress - Oxytocin - Bindung - Social-Salience - allostatische Theorie

Key words

Stress - oxytocin - relationship - social salience - allostatic theory

^* Beide Autoren trugen gleichermaßen zur Entstehung dieses Manuskripts bei.

Publication History

Article published online:
03 March 2023

• Literatur

• 1 Carter CS. Oxytocin Pathways and the Evolution of Human Behavior. Annu Rev Psychol 2014; 65: 17-39
• 2 Leng G, Caquineau C, Sabatier N. Regulation of Oxytocin Secretion. Vitam Horm 2005; 71: 27-58
• 3 de Jong TR, Neumann ID. Oxytocin and aggression. In: Current Topics in Behavioral Neurosciences. Berlin: Springer Verlag; 2018: 175-192
• 4 Neumann ID, Landgraf R. Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci 2012; 35: 649-659
• 5 American Psychiatric Association Diagnostisches und statistisches Manual psychischer Störungen DSM-5 In : Falkai P, Wittchen HU (Hrsg.). Göttingen: Hogrefe; 2018
• 6 Cooper J. Taschenführer zur ICD-10-Klassifikation psychischer Störungen. 6. Aufl. Bern: Huber; 2012
• 7 Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 2001; 49: 1023-1039
• 8 Shapero BG, Black SK, Liu RT. et al Stressful Life Events and Depression Symptoms: The Effect of Childhood Emotional Abuse on Stress Reactivity. J Clin Psychol 2014; 70: 209-223
• 9 Norman RE, Byambaa M, De R. et al The Long-Term Health Consequences of Child Physical Abuse, Emotional Abuse, and Neglect: A Systematic Review and Meta-Analysis. PLoS Med 2012; 09: e1001349
• 10 Heim C, Young LJ, Newport DJ. et al Lower CSF oxytocin concentrations in women with a history of childhood abuse. Mol Psychiatry 2009; 14: 954-958
• 11 Jurek B, Neumann ID. The Oxytocin Receptor: From Intracellular Signaling to Behavior. Physiol Rev 2018; 98: 1805-1908
• 12 Quintana DS, Guastella AJ. An Allostatic Theory of Oxytocin. Trends Cogn Sci 2020; 24: 515-528
• 13 Kalinichev M, Easterling KW, Plotsky PM. et al Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats. Pharmacol Biochem Behav 2002; 73: 131-140
• 14 Watt DF, Panksepp J. Depression: An Evolutionarily Conserved Mechanism to Terminate Separation Distress? A Review of Aminergic, Peptidergic, and Neural Network Perspectives. Neuropsychoanalysis 2009; 11: 7-51
• 15 Vargas J, Junco M, Gomez C. et al Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats. PLoS One 2016; 11: e0162665
• 16 Engelmann M, Landgraf R, Wotjak CT. The hypothalamic-neurohypophysial system regulates the hypothalamic- pituitary-adrenal axis under stress: An old concept revisited. Front Neuroendocrinol 2004; 25: 132-149
• 17 Koolhaas JM, Korte SM, De Boer SF. et al Coping styles in animals: Current status in behavior and stress- physiology. Neurosci Biobehav Rev 1999; 23: 925-935
• 18 Winter J, Jurek B. The interplay between oxytocin and the CRF system: regulation of the stress response. Cell Tissue Res 2019; 375: 85-91
• 19 Smith AS, Wang Z. Hypothalamic oxytocin mediates social buffering of the stress response. Biol Psychiatry 2014; 76: 281-288
• 20 Dabrowska J, Hazra R, Ahern TH. et al Neuroanatomical evidence for reciprocal regulation of the corticotrophin-releasing factor and oxytocin systems in the hypothalamus and the bed nucleus of the stria terminalis of the rat: Implications for balancing stress and affect. Psychoneuroendocrinology 2011; 36: 1312-1326
• 21 Michelsson K, Christensson K, Rothgänger H. et al Crying in separated and non-separated newborns: sound spectrographic analysis. Acta Paediatr 1996; 85: 471-475
• 22 Christensson K, Cabrera T, Christensson E. et al Separation distress call in the human neonate in the absence of maternal body contact. Acta Paediatr 1995; 84: 468-473
• 23 Kehoe P, Blass EM. Opioid-mediation of separation distress in 10-day-old rats: Reversal of stress with maternal stimuli. Dev Psychobiol 1986; 19: 385-398
• 24 Panksepp J, Nelson E, Bekkedal M. Brain Systems for the Mediation of Social Separation-Distress and Social-Reward Evolutionary Antecedents and Neuropeptide Intermediaries. Ann N Y Acad Sci 1997; 807: 78-100
• 25 Bowlby J. The making and breaking of affectional bonds. I. Aetiology and psychopathology in the light of attachment theory. An expanded version of the Fiftieth Maudsley Lecture, delivered before the Royal College of Psychiatrists, 19 November 1976. Br J Psychiatry 1977; 130: 201-210
• 26 Panksepp J. Oxytocin Effects on Emotional Processes: Separation Distress, Social Bonding, and Relationships to Psychiatric Disorders. Ann N Y Acad Sci 1992; 652: 243-252
• 27 Lim DHK, Maher ER. DNA methylation: a form of epigenetic control of gene expression. Obstet Gynaecol 2010; 12: 37-42
• 28 Goldberg AD, Allis CD, Bernstein E. Epigenetics: A Landscape Takes Shape. Cell 2007; 128: 635-638
• 29 Turner JD, D’Ambrosio C, Vögele C. et al Twin Research in the Post-Genomic Era: Dissecting the Pathophysiological Effects of Adversity and the Social Environment. Int J Mol Sci 2020; 21: 3142
• 30 Kraaijenvanger EJ, He Y, Spencer H. et al Epigenetic variability in the human oxytocin receptor (OXTR) gene: A possible pathway from early life experiences to psychopathologies. Neurosci Biobehav Rev 2019; 96: 127-142
• 31 Smearman EL, Almli LM, Conneely KN. et al Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms. Child Dev 2016; 87: 122-134
• 32 Kimmel M, Clive M, Gispen F. et al Oxytocin receptor DNA methylation in postpartum depression. Psychoneuroendocrinology 2016; 69: 150-160
• 33 Sanwald S, Widenhorn-Müller K, Montag C. et al Relation of promoter methylation of the structural oxytocin gene to critical life events in Major Depression: A case control study. J Affect Disord 2020; 276: 829-838
• 34 Sanwald S, Gahr M, Widenhorn-Müller K. et al Relation of Promoter Methylation of the Oxytocin Gene to Stressful Life Events and Depression Severity. J Mol Neurosci 2020: 70
• 35 Amico JA, Mantella RC, Vollmer RR. et al Anxiety and Stress Responses in Female Oxytocin Deficient Mice. J Neuroendocrinol 2004; 16: 319-324
• 36 Winslow JT, Insel TR. The social deficits of the oxytocin knockout mouse. Neuropeptides 2002; 36: 221-229
• 37 Amico JA, Miedlar JA, Cai HM. et al Oxytocin knockout mice: a model for studying stress-related and ingestive behaviours. Prog Brain Res 2008; 170: 53-64
• 38 Santini ZI, Koyanagi A, Tyrovolas S. et al The association between social relationships and depression: A systematic review. J Affect Disord 2015; 175: 53-65
• 39 Meaney MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 2001; 24: 1161-1192
• 40 Asselmann E, Wittchen HU, Lieb R. et al The role of the mother–child relationship for anxiety disorders and depression: results from a prospective-longitudinal study in adolescents and their mothers. Eur Child Adolesc Psychiatry 2015; 24: 451-461
• 41 Feldman R. Oxytocin and social affiliation in humans. Horm Behav 2012; 61: 380-391
• 42 Feldman R. Infant-mother and infant-father synchrony: The coregulation of positive arousal. Infant Ment Health J 2003; 24: 1-23
• 43 Feldman R. The relational basis of adolescent adjustment: Trajectories of mother-child interactive behaviors from infancy to adolescence shape adolescents’ adaptation. Attach Hum Dev 2010; 12: 173-192
• 44 Scatliffe N, Casavant S, Vittner D. et al Oxytocin and early parent-infant interactions: A systematic review. Int J Nurs Sci 2019; 06: 445-453
• 45 Love TM. Oxytocin, motivation and the role of dopamine. Pharmacol Biochem Behav 2014; 119: 49-60
• 46 Quintana DS, Rokicki J, van der Meer D. et al Oxytocin pathway gene networks in the human brain. Nat Commun 2019; 10: 1-12
• 47 Lee A, Clancy S, Fleming AS. Mother rats bar-press for pups: Effects of lesions of the mpoa and limbic sites on maternal behavior and operant responding for pup- reinforcement. Behav Brain Res 1999; 100: 15-31
• 48 Dölen G, Darvishzadeh A, Huang KW. et al Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 2013; 501: 179-184
• 49 Bartholomew K. Avoidance of Intimacy: An Attachment Perspective. J Soc Pers Relat 1990; 07: 147-178
• 50 Scharfe E, Bartholomew K. Reliability and stability of adult attachment patterns. Pers Relatsh 1994; 01: 23-43
• 51 Ellis BJ, Horn AJ, Carter CS. et al Developmental programming of oxytocin through variation in early-life stress: Four meta-analyses and a theoretical reinterpretation. Clin Psychol Rev 2021; 86: 101985
• 52 Sanson A, Bosch OJ. Dysfunctions of brain oxytocin signaling: Implications for poor mothering. Neuropharmacology 2022; 211: 109049
• 53 Lecompte V, Robins S, King L. et al Examining the role of mother-child interactions and DNA methylation of the oxytocin receptor gene in understanding child controlling attachment behaviors. Attach Hum Dev 2021; 23: 37-55
• 54 Robakis TK, Zhang S, Rasgon NL. et al Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression. Transl Psychiatry 2020; 10: 1-14
• 55 Ebner NC, Lin T, Muradoglu M. et al Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood. Int J Psychophysiol 2019; 136: 22-32
• 56 Bonanno GA, Galea S, Bucciarelli A. et al What Predicts Psychological Resilience After Disaster? The Role of Demographics, Resources, and Life Stress. J Consult Clin Psychol 2007; 75: 671-682
• 57 Pierrehumbert B, Torrisi R, Ansermet F. et al Adult attachment representations predict cortisol and oxytocin responses to stress. Attach Hum Dev 2012; 14: 453-476
• 58 Flückiger C, Del AC, Wampold BE. et al The Alliance in Adult Psychotherapy: A Meta-Analytic Synthesis. Psychotherapy 2018; 55: 316-340
• 59 Cuijpers P, Reijnders M, Huibers MJH. The Role of Common Factors in Psychotherapy Outcomes. Annu Rev Clin Psychol 2019; 15: 207-231
• 60 Zilcha-Mano S, Goldstein P, Dolev-Amit T. et al Oxytocin synchrony between patients and therapists as a mechanism underlying effective psychotherapy for depression. J Consult Clin Psychol 2021; 89: 49-57
• 61 Atzil-Slonim D, Stolowicz-Melman D, Bar-Kalifa E. et al Oxytocin Reactivity to the Therapeutic Encounter as a Biomarker of Change in the Treatment of Depression. J Couns Psychol 2022
• 62 Kosfeld M, Heinrichs M, Zak PJ. et al Oxytocin increases trust in humans. Nature 2005; 435: 673-676
• 63 Nave G, Camerer C, McCullough M. Does Oxytocin Increase Trust in Humans? A Critical Review of Research. Perspect Psychol Sci 2015; 10: 772-789
• 64 Declerck CH, Boone C, Pauwels L. et al A registered replication study on oxytocin and trust. Nat Hum Behav 2020; 04: 646-655
• 65 Tabak BA, McCullough ME, Szeto A. et al Oxytocin indexes relational distress following interpersonal harms in women. Psychoneuroendocrinology 2011; 36: 115-122
• 66 Wernicke J, Zhang Y, Felten A. et al Blood oxytocin levels are not associated with ADHD tendencies and emotionality in healthy adults. Neurosci Lett 2020; 738: 135312
• 67 Sindermann C, Luo R, Becker B. et al The role of oxytocin on self-serving lying. Brain Behav 2020; 10: e01518
• 68 Shamay-Tsoory SG, Abu-Akel A. The Social Salience Hypothesis of Oxytocin. Biol Psychiatry 2016; 79: 194-202
• 69 Sterling P, Eyer J. Allostasis: A new paradigm to explain arousal pahtology. In: Fisher S, Reason JT, Hrsg. Handbook of life stress, cognition, and health. Chichester; New York: Wiley 1988: 629-649
• 70 Ramsay DS, Woods SC. Clarifying the roles of homeostasis and allostasis in physiological regulation. Psychol Rev 2014; 121: 225-247
• 71 McEwen BS. Stress, adaptation, and disease: allostasis and allostatic load. Ann N Y Acad Sci 1998; 840: 33-44
• 72 Takayanagi Y, Onaka T. Roles of Oxytocin in Stress Responses, Allostasis and Resilience. Int J Mol Sci 2022; 23: 150
• 73 Terburg D, Scheggia D, Triana del Rio R. et al The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study. Cell 2018; 175: 723-735.e16
• 74 Onaka T, Takayanagi Y, Yoshida M. Roles of Oxytocin Neurones in the Control of Stress, Energy Metabolism, and Social Behaviour. J Neuroendocrinol 2012; 24: 587-598
• 75 American Psychiatric Association Diagnostisches und Statistisches Manual Psychischer Störungen DSM-5. 2. Aufl. Göttingen: Hogrefe Verlag; 2018
• 76 Daskalakis NP, Bagot RC, Parker KJ. et al The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology 2013; 38: 1858-1873
• 77 Montag C, Widenhorn-Müller K, Panksepp J. et al Individual differences in Affective Neuroscience Personality Scale (ANPS) primary emotional traits and depressive tendencies. Compr Psychiatry 2017; 73: 136-142
• 78 Montag C, Panksepp J. Primary emotional systems and personality: An evolutionary perspective. Front Psychol 2017; 08: 464
• 79 Panksepp J. Affective neuroscience: The foundations of human and animal emotions. New York: Oxford University Press; 2004
• 80 Lewinsohn PM. A behavioral approach to depression. In: Friedman RJ, Katz MM, Hrsg. The psychology of depression: Contemporary theory and research. New York: John Wiley & Sons, Inc.; 1974
• 81 Maier SF, Seligman ME. Learned helplessness: Theory and evidence. J Exp Psychol Gen 1976; 105: 3-46
• 82 Nandam LS, Brazel M, Zhou M. et al Cortisol and Major Depressive Disorder – Translating Findings From Humans to Animal Models and Back. Front Psychiatry 2020; 10: 974
• 83 Kennis M, Gerritsen L, van Dalen M. et al Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis. Mol Psychiatry 2020; 25: 321-338
• 84 Psarraki EE, Kokka I, Bacopoulou F. et al Is there a relation between major depression and hair cortisol? A systematic review and meta-analysis. Psychoneuroendocrinology 2021; 124: 105098
• 85 Nikkheslat N, McLaughlin AP, Hastings C. et al Childhood trauma, HPA axis activity and antidepressant response in patients with depression. Brain Behav Immun 2020; 87: 229-237
• 86 Engel S, Laufer S, Knaevelsrud C. et al The endogenous oxytocin system in depressive disorders: A systematic review and meta-analysis. Psychoneuroendocrinology 2019; 101: 138-149
• 87 Tabak BA, Rosenfield D, Sunahara CS. et al Social anxiety is associated with greater peripheral oxytocin reactivity to psychosocial stress. Psychoneuroendocrinology 2022; 140: 105712
• 88 Jobst A, Sabass L, Palagyi A. et al Effects of social exclusion on emotions and oxytocin and cortisol levels in patients with chronic depression. J Psychiatr Res 2015; 60: 170-177
• 89 Peled-Avron L, Abu-Akel A, Shamay-Tsoory S. Exogenous effects of oxytocin in five psychiatric disorders: a systematic review, meta-analyses and a personalized approach through the lens of the social salience hypothesis. Neurosci Biobehav Rev 2020; 114: 70-95
• 90 Eckstein M, Scheele D, Patin A. et al Oxytocin Facilitates Pavlovian Fear Learning in Males. Neuropsychopharmacology 2016; 41: 932-939
• 91 Kou J, Zhang Y, Zhou F. et al A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin. Psychol Med 2022; 52: 1959-1968