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Despite an estimated lifetime prevalence of 0.5–1.0% in men and high public concern, no effective treatment is known for pedophilic disorder. Here, we provide robust meta-analytic evidence

that brain activity is not generally altered in pedophilia but deviates specifically in response to sexual stimuli. We show how this meta-analysis-derived functional brain alteration pattern

in pedophiles maps onto underlying neurophysiology in terms of specific neurotransmitter systems and their corresponding gene expression as well as to behavioral aspects. We report robust

and specific associations between functional brain alterations in pedophiles and the distribution of the serotonergic 5-HT1B receptor as derived from in vivo positron emission tomography

data as well as gene expression analyses. At the functional level, the alterations related to cognitive processes including self-regulation and goal-directed behavior. These findings warrant

further investigation into the molecular mechanisms underlying pedophilia and point toward the development of specific pharmacological interventions.

Coordinates used in the meta-analyses are available from the included studies that are referenced in the Supplementary Information. Transmitter and receptor atlases are shipped with the

JuSpace Toolbox (https://github.com/juryxy/JuSpace/). Neurosynth data are available at https://neurosynth.org/. Allen Human Brain Atlas data are available from https://human.brain-map.org/.

ALE software is available at https://www.brainmap.org/ale/, the JuBrain Anatomy Toolbox 3.0 at https://github.com/inm7/jubrain-anatomy-toolbox, the JuSpace Toolbox 1.4 at

https://github.com/juryxy/JuSpace, Neurosynth 0.3.8 at https://github.com/neurosynth/neurosynth, neuromaps 0.0.3 at https://github.com/netneurolab/neuromaps, and the Talairach Client 2.4.3

at http://www.talairach.org/client.html.

Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

Gereon J. Schnellbächer, Viktoria Pietsch, Katrin Sakreida & Timm B. Poeppl

Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Jülich, Germany

Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

McConnell Brain Imaging Centre, Montréal Neurological Institute, McGill University, Montréal, Quebec, Canada

Faculty of Psychology, FernUniversität in Hagen (University of Hagen), Hagen, Germany

Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany

Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Regensburg, Regensburg, Germany

T.B.P. designed the study; S.B.E. gave conceptual advice. V.P., K.S. and T.B.P. gathered data for the meta-analyses. T.B.P. conducted the meta-analyses with advice of S.B.E. J.D. and T.B.P.

conducted the neurotransmitter analyses. J.D. performed the gene expression analyses. J.Y.H. and R.D.M. provided the behavioral profiling. G.S. and T.B.P. wrote the manuscript. A.M., I.R.

and M.W. discussed the results and implications. All authors commented on the manuscript at all stages.

Nature Mental Health thanks Kirsten Jordan, Cristina Scarpazza and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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