title: Serotonergic modulation of resting state default mode network connectivity in healthy women.
abstract: The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20-31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Helmbold
authors.affiliation: Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zvyagintsev
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Dahmen
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.
authors.forename: C S
authors.initials: CS
authors.lastname: Biskup
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bubenzer-Busch
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.
authors.forename: T J
authors.initials: TJ
authors.lastname: Gaber
authors.affiliation: Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Klasen
authors.affiliation: Department of Pharmacy, RWTH Aachen University, Aachen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Eisert
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.|Institute for Neuroscience and Medicine, Jülich Research Centre, Jülich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Konrad
authors.affiliation: Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Habel
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Herpertz-Dahlmann
authors.affiliation: RWTH Aachen University, Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Aachen, Germany. florian.zepf@uwa.edu.au.|Jülich Aachen Research Alliance, JARA Translational Brain Medicine, Aachen, Germany. florian.zepf@uwa.edu.au.|Institute for Neuroscience and Medicine, Jülich Research Centre, Jülich, Germany. florian.zepf@uwa.edu.au.|Department of Child and Adolescent Psychiatry, School of Psychiatry & Clinical Neurosciences and School of Paediatrics & Child Health, The University of Western Australia, Perth, WA, Australia. florian.zepf@uwa.edu.au.|Specialised Child and Adolescent Mental Health Services (CAMHS), Department of Health in Western Australia, Perth, WA, Australia. florian.zepf@uwa.edu.au.
authors.forename: F D
authors.initials: FD
authors.lastname: Zepf
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D000596:Amino Acids / Q000008:administration & dosage; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005498:Follicular Phase / Q000502:physiology*; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging; D009415:Nerve Net / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D010296:Parietal Lobe / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D012146:Rest / Q000502:physiology* / Q000523:psychology; D012701:Serotonin / Q000096:biosynthesis*; D013850:Thinking / Q000187:drug effects / Q000502:physiology; D014364:Tryptophan / Q000008:administration & dosage / Q000172:deficiency
chemical_list: D000596:Amino Acids; D012701:Serotonin; D014364:Tryptophan
keywords: Default mode network; Functional connectivity; Impulsivity; Resting state; Serotonin; Tryptophan depletion