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Reduced neuronal responsiveness to visual sexual stimuli in a pedophile treated with a long-acting LH-RH agonist.

The introduction of long-acting luteinizing hormone-releasing hormone (LH-RH) agonists in the early 1990s opened up a new era in the management of paraphilic disorders. Despite the fact that they are not yet officially approved and may have significant side effects [1], there is first evidence for their efficiency especially in suppressing pedophilic urges and arousability [2]. In the past 2 years, a growing body of literature has appeared on functional brain correlates of sexual arousal in clinical populations [3] and particularly with regard to pedophilia, where also morphological deficiencies could be verified [4–8]. Here, we report first evidence of an altered neuronal response pattern in a pedophile treated with an LH-RH agonist. The brain activation pattern in response to sexual stimuli was analyzed in an incarcerated pedophilic forensic inpatient (age: 38.4 years) who matches the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for pedophilia, exclusive type (female children), and who has sexually abused at least four prepubescent girls (criminal record). At the time of assessment, the patient had been solely treated with Trenantone® (Takeda Pharma, Aachen, Germany) over a period of 3 years (11.25 mg leuprolide acetate depot injection every 3 months), and with supportive psychotherapy. Serum testosterone levels were constantly suppressed to castration levels after 4 weeks of treatment (4.31 ng/mL prior to treatment and constantly 0.6 ng/mL after 4 weeks). As assessed by visual analog scales every 3 months, the patient reported a gradual reduction in deviant fantasies and masturbation frequency over time, finally resulting in a decrease of more than 90% compared with his base level, after a 9-month period of application. The functional magnetic resonance imaging sessions consisted of several epochs of sexually arousing visual stimuli alternating with neutral visual stimuli as used in the study mentioned earlier [4]. Whole body slides of nude girls and women were used as sexually arousing stimuli; the control stimuli were slides of the same groups in dressed mode (for details on study design and data analyses, please see Schiffer et al. [4]). Viewing slides of dressed vs. undressed women revealed no differences in neuronal activation in the current case, whereas viewing slides of dressed vs. undressed girls led to significantly stronger activation of the right frontopolar prefrontal cortex (FPPFC), the left subgenual anterior cingulate (ACC), and the bilateral superior temporal cortex (STC), as well as the right cuneus and both middle occipital gyri (Figure 1A). Additionally, we examined the (un)dressed women vs. (un)dressed girls contrast. There were no significant differences while viewing preferred vs. unpreferred persons in a dressed mode. In an undressed mode only the undressed girls > undressed women contrast revealed significantly stronger activation in the dorsolateral prefrontal cortex Brodmann Area (BA) 9/46, the STC (BA 38), the superior parietal lobule (BA 7), and both middle occipital gyri (Figure 1B). However, compared with the group of unmedicated heterosexual pedophiles [4], the patient treated with LH-RH agonist showed no activation of the (hypo)thalamus, amygdala, insula, substantia nigra, hippocampus, or the rostral part of the ACC, although these brain areas are welldefined for the processing of emotional and autonomic aspects of sexual behavior [4,9] and were activated in all subjects in the aforementioned group with the given threshold [4]. We therefore suggest that the treatment of pedophiles with an LH-RH agonist and the consequent strong decrease in testosterone levels may suppress the neuronal processing of sexual stimuli primarily in subcortical brain areas which are known to be significantly modulated by sex steroids [10]. Other brain areas, in contrast, remain almost unaffected, as indicated by the activation of the FPPFC, ACC (ventral part), and STC in this patient. Even though this observation is uncon892 Letters to the Editor