The influence of endogenous testosterone and exogenous oxytocin on the response to baby schema in the female brain Dissertation Zur Erlangung der Würde des Doktors der Naturwissenschaften des Fachbereichs Biologie der Fakultät für Mathematik, Informatik und Naturwissenschaften Universität Hamburg vorgelegt von Sarah Katharina Charlotte Holtfrerich Hamburg, 2018 Gutachter der Dissertation: Prof. Jun. Dr. Esther K. Diekhof Prof. Dr. Christian Büchel Tag der Disputation: 31.07.2018 Content I. Abstract ...........................................................................................................................................- 1 - II. Zusammenfassung .........................................................................................................................- 3 - III. Abbreviations .................................................................................................................................- 5 - 1. Introduction ....................................................................................................................................- 6 - 1.1. The hormonal basis of reproduction and caretaking behavior ..............................................- 6 - 1.1.1. Oxytocin ..........................................................................................................................................- 8 - 1.1.1.1. The role of oxytocin in general nurturing behavior .................................................................- 8 - 1.1.1.2. The physiology of oxytocin ....................................................................................................... - 10 - 1.1.1.3. Oxytocin reception and pathways through the brain ............................................................ - 12 - 1.1.2. Testosterone ................................................................................................................................ - 13 - 1.1.2.1. The role of testosterone in general nurturing behavior ........................................................ - 13 - 1.1.2.2. The physiology of testosterone................................................................................................. - 14 - 1.1.2.3. Testosterone reception and pathways through the brain ..................................................... - 16 - 1.1.3. The interaction of oxytocin and testosterone in parental behavior .................................... - 17 - 1.2. Baby schema as a key stimulus for caretaking behavior ....................................................... - 20 - 1.3. Design and measures of the present studies ........................................................................... - 22 - 1.3.1. Study objective ............................................................................................................................ - 23 - 1.3.2. Measuring selective attention – A means to operationalize the influence of the baby schema on cognitive and neural processing .......................................................................................... - 24 - 1.3.3. Measuring brain activity with functional magnetic resonance imaging .............................. - 26 - 1.3.4. Salivary hormone measurements .............................................................................................. - 28 - 1.3.5. Hormonal intervention .............................................................................................................. - 29 - 1.3.6. Hypotheses of the behavioral study ......................................................................................... - 30 - 1.3.7. Hypotheses of the fMRI study ................................................................................................. - 31 - 2. Publications .................................................................................................................................. - 32 - 2.1. Publication I ................................................................................................................................. - 32 - 2.2. Publication II ............................................................................................................................... - 52 - 2.2.1. Supplementary material and methods of Publication II ....................................................... - 63 - 3. Discussion .................................................................................................................................... - 73 - 3.1. The endocrinology of caretaking behavior ............................................................................. - 74 - 3.1.1. Influences of testosterone on caretaking behavior ................................................................ - 75 - 3.1.2. Influences of oxytocin on caretaking behavior ...................................................................... - 77 - 3.1.3. Interaction of oxytocin and testosterone in the modulation of caretaking behavior....... - 79 - 3.2. The neuroendocrinology of the processing of infant faces ................................................. - 83 - 3.2.1. Baby schema as a key stimulus motivates action in the female brain ................................. - 83 - 3.2.2. The interaction of testosterone and oxytocin in the processing of infant faces in the female brain .............................................................................................................................................. - 86 - 3.2.3. Other possible neuroendocrine interactions in the modulation of general nurturing behavior ........................................................................................................................................ - 88 - 3.2.4. Transferability of the results to other subjects ....................................................................... - 90 - 3.3. Evidence for hormonal interactions in the response to infant faces .................................. - 91 - 3.4. Evolutionary relevance of the findings ................................................................................... - 93 - 3.5. Clinical relevance of the findings ............................................................................................. - 94 - 3.6. Conclusion ................................................................................................................................... - 96 - 3.7. Outlook ........................................................................................................................................ - 97 - 4. References .................................................................................................................................... - 99 - 5. Figure Index ............................................................................................................................... - 116 - 6. Table Index ................................................................................................................................ - 116 - 7. Publications ................................................................................................................................ - 117 - 8. Eidesstattliche Versicherung ................................................................................................... - 118 - 9. Danksagung ............................................................................................................................... - 119 - I. Abstract I. Abstract The neuropeptide oxytocin is well known for its crucial role in childbirth and bonding. It seems to influence caretaking behaviors by modulating complex neuroendocrine reward systems. Contrary to oxytocin, high concentrations of the steroid hormone testosterone seem to antagonize caretaking behaviors. Whereas high testosterone concentrations were associated with competitive and defensive behaviors, low testosterone concentrations may support caretaking behaviors. For instance, the decrease of testosterone in new mothers and fathers is thought to be adaptive to promote parental care, while a decrease of oxytocin in new mothers was associated with postpartum depression risk. Interestingly, some behavioral effects of oxytocin may be steroid hormone dependent. Equally, oxytocin seems to modulate different steroid dependent reproductive functions like erection, ejaculation, orgasm, labor induction and lactation in mammals. Reproductive success in mammals greatly depends on the caretaking effort of the parents or alloparents. A lack of caretaking behavior would probably result in neglect which could further cause the death of the vulnerable offspring. Therefore it may be adaptive that infants wear a key stimulus in the face that automatically elicits caretaking behavior in adults: the baby schema. Besides parental care, different kinds of mammals (especially primates) show alloparental care. Therefore it is likely that not only hormones involved in pregnancy and lactation influence maternal behavior, but that a neuroendocrine mechanism may be involved in the regulation of caretaking behavior in general. By reason of their important impact on reproduction and their inverse influences on caretaking behaviors it was the aim of this doctoral thesis to investigate the modulatory influence of testosterone and oxytocin on the processing of and the sensitivity for the baby schema and how both hormones interact in the modulation of a basic aspect of caretaking behavior, selective attention towards infants. For this, I used a combination of different established methods to investigate