Objectives: Pedophilia (P) is a psychiatric disease associated with sexual attraction toward children and often accompanied by child sexual offending (CSO). Consequently, it is important to address the understanding of executive dysfunctions that may increase the probability of CSO. Moreover, this research field has been lacking to disentangle executive deficits associated with pedophilia (as a deviant sexual preference) from those associated with CSO (as a deviant sexual behavior). Methods: The German multi-sided research network NeMUP offers the opportunity to overcome these limitations. By applying the Cambridge Automated Neuropsychological Test Battery in four carefully matched groups of men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual offending against children; (3) child molesters without pedophilia (N=19), and (4) non-offending controls (N=49), we were able to analyze executive functioning in pedophilia and CSO independently. Results: Both CSO groups as compared to both non-CSO groups exhibited worsened response inhibition ability. However, only non-pedophilic offenders showed additionally disabled strategy use ability. Regarding set-shifting abilities, the P+CSO group showed the best performance. We also found that performances were affected by age: only in pedophiles, response inhibition worsened with age, while age-related deficits in set-shifting abilities were restricted to non-pedophilic participants. The latter also differentiated between both sexual preference groups. Conclusions: Our results are the first to demonstrate that executive dysfunctions are related to offense status rather than pedophilic preference. Furthermore, there was evidence for differentiating age and performance correlations between pedophiles and non-pedophiles, which warrants further investigation. (JINS, 2017, 23, 460–470)

Background: Patients with neurofibromatosis type 1 (NF1) develop benign (BPNST), premalignant atypical (ANF), and malignant (MPNST) peripheral nerve sheath tumors. Radiological differentiation of these entities is challenging. Therefore, we aimed to evaluate the value of a magnetic resonance imaging (MRI)-based radiomics machine-learning (ML) classifier for differentiation of these three entities of internal peripheral nerve sheath tumors in NF1 patients. Methods: MRI was performed at 3T in 36 NF1 patients (20 male; age: 31 ± 11 years). Segmentation of 117 BPNSTs, 17 MPNSTs, and 8 ANFs was manually performed using T2w spectral attenuated inversion recovery sequences. One hundred seven features per lesion were extracted using PyRadiomics and applied for BPNST versus MPNST differentiation. A 5-feature radiomics signature was defined based on the most important features and tested for signature-based BPNST versus MPNST classification (random forest [RF] classification, leave-one-patient-out evaluation). In a second step, signature feature expressions for BPNSTs, ANFs, and MPNSTs were evaluated for radiomics-based classification for these three entities. Results: The mean area under the receiver operator characteristic curve (AUC) for the radiomics-based BPNST versus MPNST differentiation was 0.94, corresponding to correct classification of on average 16/17 MPNSTs and 114/117 BPNSTs (sensitivity: 94%, specificity: 97%). Exploratory analysis with the eight ANFs revealed intermediate radiomic feature characteristics in-between BPNST and MPNST tumor feature expression. Conclusion: In this proof-of-principle study, ML using MRI-based radiomics characteristics allows sensitive and specific differentiation of BPNSTs and MPNSTs in NF1 patients. Feature expression of premalignant atypical tumors was distributed in-between benign and malignant tumor feature expressions, which illustrates biological plausibility of the considered radiomics characteristics.

Plexiform neurofibromas can transform into atypical neurofibromas (ANF) and then further progress to aggressive malignant peripheral nerve sheath tumors (MPNST). ANF have been described to harbor distinct histological features and frequent loss of CDKN2A/B. However, histological evaluation may be rater-dependent, and detailed knowledge about the molecular mechanisms of malignant transformation is scarce. In general, malignant transformation can be accompanied by significant epigenetic changes, and global DNA methylation profiling is able to differentiate relevant tumor subgroups. Therefore, epigenetic profiling might provide a valuable tool to distinguish and characterize ANF with differing extent of histopathological atypia from neurofibromas and MPNST. We investigated 40 tumors histologically diagnosed as ANF and compared their global methylation profile to other peripheral nerve sheath tumors. Unsupervised class discovery and t-SNE analysis indicated that 36/40 ANF cluster with benign peripheral nerve sheet tumors with clear separation from MPNST. 21 ANF formed a molecularly distinct cluster in proximity to schwannomas. Tumors in this cluster had frequent heterozygous or homozygous loss of CDKN2A/B and significantly more lymphocyte infiltration than MPNST, schwannomas, and NF. Few ANF clustered closely with neurofibromas, schwannomas, or MPNST, raising the question, whether diagnosis based on histological features alone might pose a risk to both over- and underestimate the aggressiveness of these lesions. Our data suggest that ANF with varying histological morphology show distinct epigenetic similarities and cluster in proximity to benign peripheral nerve sheath tumor entities. Future investigations should pay special respect to correlating this methylation pattern to clinical outcome.

High prevalence of child sexual offending stand in contradiction to low conviction rates (one-tenth at most) of child sexual offenders (CSOs). Little is known about possible differences between convicted and non-convicted pedophilic CSOs and why only some become known to the judicial system. This investigation takes a closer look at the two sides of “child sexual offending” by focusing on clinical and neurobiological characteristics of convicted and non-convicted pedophilic CSOs as presented in the Neural Mechanisms Underlying Pedophilia and sexual offending against children (NeMUP)*-study. Seventy-nine male pedophilic CSOs were examined, 48 of them convicted. All participants received a thorough clinical examination including the structured clinical interview (SCID), intelligence, empathy, impulsivity, and criminal history. Sixty-one participants (38 convicted) underwent an inhibition performance task (Go/No-go paradigm) combined with functional magnetic resonance imaging (fMRI). Convicted and non-convicted pedophilic CSOs revealed similar clinical characteristics, inhibition performances, and neuronal activation. However, convicted subjects’ age preference was lower (i.e., higher interest in prepubescent children) and they had committed a significantly higher number of sexual offenses against children compared to non-convicted subjects. In conclusion, sexual age preference may represent one of the major driving forces for elevated rates of sexual offenses against children in this sample, and careful clinical assessment thereof should be incorporated in every preventive approach.

A pedophilic disorder is characterised by abnormal sexual urges towards prepubescent children. Child abusive behavior is frequently a result of lack of behavioral inhibition and current treatment options entail, next to suppressing unchangeable sexual orientation, measures to increase cognitive and attentional control. We tested, if in brain regions subserving attentional control of behavior and perception of salient stimuli, such inhibition deficit can be observed also on the level of inhibitory neurotransmitters. We measured GABA concentration in the dorsal anterior cingulate cortex (dACC) and in a control region, the pregenual anterior cingulate cortex (pgACC) in pedophilic sex offenders (N = 13) and matched controls (N = 13) using a 7 Tesla STEAM magnetic resonance spectroscopy (MRS). In dACC but not in the control region pedophilic sex offenders showed reduced GABA/Cr concentrations compared to healthy controls. The reduction was robust after controlling for potential influence of age and gray matter proportion within the MRS voxel (p < 0.04). Importantly, reduced GABA/Cr in patients was correlated with lower self-control measured with the Barratt Impulsiveness Scale (p = 0.028, r = -0.689). In a region related to cognitive control and salience mapping, pedophilic sex offenders showed reduction of the inhibitory neurotransmitter GABA which may be seen as a neuronal correlate of inhibition and behavioral control.

Artificial intelligence has the potential to increase economic value in radiology, but its financial impact is highly context dependent, varying with task complexity, diagnostic performance, payment models, and willingness-to-pay thresholds for quality-adjusted life-year gains.