title: Sex differences in the functional connectivity of the amygdalae in association with cortisol.
abstract: Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical School, University of Tübingen, Germany; Jülich-Aachen-Research Alliance, Translational Brain Medicine, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany. Electronic address: lydia.kogler@med.uni-tuebingen.de.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kogler
authors.affiliation: Institute of Neuroscience und Medicine, INM-1, Research Centre Jülich, Jülich, Germany; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Veronika I
authors.initials: VI
authors.lastname: Müller
authors.affiliation: Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Seidel
authors.affiliation: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Centre for Medical Physics and Biomedical Engineering, Medical University, Vienna, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Boubela
authors.affiliation: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Centre for Medical Physics and Biomedical Engineering, Medical University, Vienna, Austria.
authors.forename: Klaudius
authors.initials: K
authors.lastname: Kalcher
authors.affiliation: MR Centre of Excellence, Medical University of Vienna, Vienna, Austria; Centre for Medical Physics and Biomedical Engineering, Medical University, Vienna, Austria; Neuropsychiatry Division, Department of Psychiatry, Medical School, University of Pennsylvania, Philadelphia, USA.
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.affiliation: Jülich-Aachen-Research Alliance, Translational Brain Medicine, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; Institute of Neuroscience und Medicine, INM-6, Research Centre Jülich, Research Centre Jülich, Jülich, Germany; JARA BRAIN Institute 1: Structure Function Relationship.
authors.forename: Ute
authors.initials: U
authors.lastname: Habel
authors.affiliation: Neuropsychiatry Division, Department of Psychiatry, Medical School, University of Pennsylvania, Philadelphia, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Institute of Neuroscience und Medicine, INM-1, Research Centre Jülich, Jülich, Germany; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Eickhoff
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical School, University of Tübingen, Germany; Institute of Neuroscience und Medicine, INM-1, Research Centre Jülich, Jülich, Germany; Jülich-Aachen-Research Alliance, Translational Brain Medicine, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Derntl
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D012463:Saliva / Q000378:metabolism*; D012737:Sex Factors; D014018:Tissue Distribution
chemical_list: D012739:Gonadal Steroid Hormones; D006854:Hydrocortisone
keywords: Cortisol; Frontal cortex; Hippocampus; Resting-state; Striatum; Task-independent