Abstract
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.
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Data availability
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/.
Code availability
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.
References
von Krafft-Ebing, R. Psychopathia sexualis: Mit Besonderer Berücksichtigung der conträren Sexualempfindung: Eine klinisch-forensische Studie (Verlag von F. Enke, 1898).
Devereux, G. Why Oedipus killed Laius; a note on the complementary Oedipus complex in Greek drama. Int. J. Psychoanal. 34, 132–141 (1953).
Ungaretti, J. R. Pederasty, heroism, and the family in classical Greece. J. Homosex. 3, 291–300 (1978).
Hughes, J. R. Review of medical reports on pedophilia. Clin. Pediatr. (Phila.) 46, 667–682 (2007).
Green, R. Is pedophilia a mental disorder? Arch. Sex. Behav. 31, 467–471 (2002).
de Waal, F. B. M. in Pedophilia (ed. Feierman, J. R.) 378–393 (Springer, 1990).
Seto, M. C. Pedophilia. Annu. Rev. Clin. Psychol. 5, 391–407 (2009).
Mokros, A., Osterheider, M. & Nitschke, J. Pedophilia. Prevalence, etiology, and diagnostics. Nervenarzt 83, 355–358 (2012).
Mokros, A. & Habermeyer, E. Regression to the mean mimicking changes in sexual arousal to child stimuli in pedophiles. Arch. Sex. Behav. 45, 1863–1867 (2016).
Muller, K. et al. Changes in sexual arousal as measured by penile plethysmography in men with pedophilic sexual interest. J. Sex. Med. 11, 1221–1229 (2014).
Beier, K. M. et al. The German Dunkelfeld project: a pilot study to prevent child sexual abuse and the use of child abusive images. J. Sex. Med. 12, 529–542 (2015).
Landgren, V. et al. Effect of gonadotropin-releasing hormone antagonist on risk of committing child sexual abuse in men with pedophilic disorder: a randomized clinical trial. JAMA Psychiatry 77, 897–905 (2020).
Fazio, R. L. Toward a neurodevelopmental understanding of pedophilia. J. Sex. Med. 15, 1205–1207 (2018).
Tenbergen, G. et al. The neurobiology and psychology of pedophilia: recent advances and challenges. Front. Hum. Neurosci. 9, 344 (2015).
Jordan, K. et al. Are there any biomarkers for pedophilia and sexual child abuse? A review. Front. Psychiatry 10, 940 (2019).
Mohnke, S. et al. Brain alterations in paedophilia: a critical review. Prog. Neurobiol. 122, 1–23 (2014).
Scarpazza, C. et al. Idiopathic and acquired pedophilia as two distinct disorders: an insight from neuroimaging. Brain Imaging Behav. 15, 2681–2692 (2021).
Eickhoff, S. B. et al. Activation likelihood estimation meta-analysis revisited. Neuroimage 59, 2349–2361 (2012).
Eickhoff, S. B. et al. Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty. Hum. Brain Mapp. 30, 2907–2926. (2009).
Turkeltaub, P. E. et al. Meta-analysis of the functional neuroanatomy of single-word reading: method and validation. Neuroimage 16, 765–780 (2002).
Turkeltaub, P. E. et al. Minimizing within-experiment and within-group effects in activation likelihood estimation meta-analyses. Hum. Brain Mapp. 33, 1–13 (2012).
Yarkoni, T. et al. Large-scale automated synthesis of human functional neuroimaging data. Nat. Methods 8, 665–670 (2011).
Poeppl, T. B. et al. A view behind the mask of sanity: meta-analysis of aberrant brain activity in psychopaths. Mol. Psychiatry 24, 463–470 (2019).
Polisois-Keating, A. & Joyal, C. C. Functional neuroimaging of sexual arousal: a preliminary meta-analysis comparing pedophilic to non-pedophilic men. Arch. Sex. Behav. 42, 1111–1113 (2013).
Poeppl, T. B. et al. The functional neuroanatomy of male psychosexual and physiosexual arousal: a quantitative meta-analysis. Hum. Brain Mapp. 35, 1404–1421 (2014).
Stoleru, S. et al. Functional neuroimaging studies of sexual arousal and orgasm in healthy men and women: a review and meta-analysis. Neurosci. Biobehav. Rev. 36, 1481–1509 (2012).
Joyal, C. C. et al. The neurobiological origins of pedophilia: not that simple. J. Sex. Med. 16, 153–154 (2019).
Gerwinn, H. et al. Clinical characteristics associated with paedophilia and child sex offending—differentiating sexual preference from offence status. Eur. Psychiatry 51, 74–85 (2018).
Massau, C. et al. Executive functioning in pedophilia and child sexual offending. J. Int. Neuropsychol. Soc. 23, 460–470 (2017).
Dillien, T. et al. The neuropsychology of child sexual offending: a systematic review. Aggress. Violent Behav. 54, 101406 (2020).
Turner, D. & Rettenberger, M. Neuropsychological functioning in child sexual abusers: a systematic review. Aggress. Violent Behav. 54, 101405 (2020).
Bitran, D. & Hull, E. M. Pharmacological analysis of male rat sexual behavior. Neurosci. Biobehav. Rev. 11, 365–389 (1987).
Teodorov, E. et al. Prenatal treatment with picrotoxin promotes heterotypical sexual behavioral and neurochemical changes in male rat offspring. Brain Res. 1069, 113–119 (2006).
Teodorov, E. et al. Effects of perinatal picrotoxin and sexual experience on heterosexual and homosexual behavior in male rats. Neurotoxicol. Teratol. 24, 235–245 (2002).
Bernardi, M. M. et al. Maternal exposure to picrotoxin modifies the response of the GABAA receptor during sexual behavior of adult male rat offspring. Behav. Pharmacol. 23, 703–709 (2012).
Bernardi, M. M. et al. Maternal treatment with picrotoxin in late pregnancy improved female sexual behavior but did not alter male sexual behavior of offspring. Behav. Pharmacol. 24, 282–290 (2013).
Davis, A. M. et al. Developmental sex differences in amino acid neurotransmitter levels in hypothalamic and limbic areas of rat brain. Neuroscience 90, 1471–1482 (1999).
Ristow, I. et al. Pedophilic sex offenders are characterised by reduced GABA concentration in dorsal anterior cingulate cortex. Neuroimage Clin. 18, 335–341 (2018).
Liu, Y. et al. Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice. Nature 472, 95–99 (2011).
Fernandez-Guasti, A. & Escalante, A. Role of presynaptic serotonergic receptors on the mechanism of action of 5-HT1A and 5-HT1B agonists on masculine sexual behaviour: physiological and pharmacological implications. J. Neural Transm. Gen. Sect. 85, 95–107 (1991).
Fernandez-Guasti, A., Escalante, A. & Agmo, A. Inhibitory action of various 5-HT1B receptor agonists on rat masculine sexual behaviour. Pharmacol. Biochem. Behav. 34, 811–816 (1989).
Fernandez-Guasti, A. et al. Stimulation of 5-HT1A and 5-HT1B receptors in brain regions and its effects on male rat sexual behaviour. Eur. J. Pharmacol. 210, 121–129 (1992).
Rodriguez-Manzo, G. et al. Participation of 5-HT(1B) receptors in the inhibitory actions of serotonin on masculine sexual behaviour of mice: pharmacological analysis in 5-HT(1B) receptor knockout mice. Br. J. Pharmacol. 136, 1127–1134 (2002).
Angoa-Perez, M. et al. Brain serotonin signaling does not determine sexual preference in male mice. PLoS ONE 10, e0118603 (2015).
Jahn, K. et al. Serotonin system-associated genetic and epigenetic changes in pedophilia and child sexual offending. J. Psychiatr. Res. 145, 60–69 (2021).
Angoa-Perez, M. & Kuhn, D. M. Neuroanatomical dichotomy of sexual behaviors in rodents: a special emphasis on brain serotonin. Behav. Pharmacol. 26, 595–606 (2015).
Cohen, L. J. & Galynker, I. Identifying psychological traits potentially subserving aberrant motivation or inhibitory failure in pedophilic behavior. Isr. J. Psychiatry Relat. Sci. 49, 280–290 (2012).
Golec, K. et al. Aberrant orbitofrontal cortex reactivity to erotic cues in compulsive sexual behavior disorder. J. Behav Addict 10, 646–656 (2021).
Klucken, T. et al. Altered appetitive conditioning and neural connectivity in subjects with compulsive sexual behavior. J. Sex. Med. 13, 627–636 (2016).
Liberg, B. et al. Neural and behavioral correlates of sexual stimuli anticipation point to addiction-like mechanisms in compulsive sexual behavior disorder. J. Behav. Addict. 11, 520–532 (2022).
Muller, V. I. et al. Ten simple rules for neuroimaging meta-analysis. Neurosci. Biobehav. Rev. 84, 151–161 (2018).
Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Brit. Med. J. 372, n71 (2021).
Nichols, H. & Molinder, I. Multiphasic Sex Inventory (Crime and Victim Psychology Specialists, 1984).
Laird, A. R. et al. Comparison of the disparity between Talairach and MNI coordinates in functional neuroimaging data: validation of the Lancaster transform. Neuroimage 51, 677–683 (2010).
Eickhoff, S. B. et al. Behavior, sensitivity, and power of activation likelihood estimation characterized by massive empirical simulation. Neuroimage 137, 70–85 (2016).
Eickhoff, S. B. et al. Testing anatomically specified hypotheses in functional imaging using cytoarchitectonic maps. Neuroimage 32, 570–582 (2006).
Eickhoff, S. B. et al. Assignment of functional activations to probabilistic cytoarchitectonic areas revisited. Neuroimage 36, 511–521 (2007).
Eickhoff, S. B. et al. A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25, 1325–1335 (2005).
Lancaster, J. L. et al. Automated Talairach atlas labels for functional brain mapping. Hum. Brain Mapp. 10, 120–131 (2000).
Collins, D. L. et al. Automatic 3-D model-based neuroanatomical segmentation. Hum. Brain Mapp. 3, 190–208 (1995).
Dukart, J. et al. JuSpace: a tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps. Hum. Brain Mapp. 42, 555–566 (2021).
Gryglewski, G. et al. Spatial analysis and high resolution mapping of the human whole-brain transcriptome for integrative analysis in neuroimaging. Neuroimage 176, 259–267 (2018).
Poldrack, R. A. et al. The cognitive atlas: toward a knowledge foundation for cognitive neuroscience. Front. Neuroinform. 5, 17 (2011).
Markello, R. D. et al. neuromaps: structural and functional interpretation of brain maps. Nat. Methods 19, 1472–1479 (2022).
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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.
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Schnellbächer, G.J., Dukart, J., Hansen, J.Y. et al. Aberrant brain activity in pedophilia links to receptor distribution, gene expression, and behavior. Nat. Mental Health 1, 615–622 (2023). https://doi.org/10.1038/s44220-023-00105-0
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DOI: https://doi.org/10.1038/s44220-023-00105-0