Understanding of the neurobiology of sexual functioning, both normal and deviant, is incomplete. Nevertheless, it is clear that sexual interest and function derive from both the central nervous system and endocrine factors. In normal sexual arousal, central nervous system involvement includes a cascade of connections from the neocortex to the limbic system and the hypothalamus, particularly the preoptic area and the brainstem (113). Sexual arousal begins via either sensory input, such as tactile, visual or olfactory stimulation, or via fantasy in the neocortex. This cortical arousal propagates through the limbic system and hypothalamus to enable a progression of physiologic events that promote sexual behaviors and orgasm. Subcortical brain areas are important for sexual functioning and include the limbic system and the preoptic nuclei in the hypothalamus. Both peptides, such as beta endorphin and oxytocin, and LHRH modulate sexual behavior in animals.
The role of monoamines is also important in normal sexuality. Dopamine appears to enhance sexual arousal with particular activity in the mesolimbic system, whereas serotonin diminishes sexual drive and arousal (114,115). Prolac-tin inhibits dopamine, resulting in diminished libidinal drive. Lowering prolactin levels via bromocriptine in women with pituitary adenomas has been shown to increase libidinal drive.
Endocrine factors are also relevant to libidinal drive. The role of estrogen in normal sexuality is not fully elucidated but it is evident that estrogen affects serotonin receptors as well as regulates beta endorphin, a peptide that has reduced sexual drive in animal studies (116). Progesterone may also lower sexual drive.
Regarding understanding paraphilic dysregulation from a biological perspective, the most compelling data is found in studies with androgens. It is known that testosterone levels strongly correlate with sexual drive in women, and aggressive sexual offenders often are found to have higher androgen levels than controls (117,118). Among the most robust data supporting biological factors underlying sexually deviant behavior is the elevation of androgen levels found in convicted rapists (119). However, the implications of these findings for the paraphilias are unclear at this time.
Early biological hypotheses regarding the paraphilias included Epstein's theory of phylogenetic preparedness of fetishism (120). He observed that a rubber boot, but not leather, evoked penile erection and ejaculation in a chimpanzee, suggesting that the fetishistic attraction to an unusal object is not limited to humans. Epstein speculated that the wet surface of the boot bore a relationship to the female chimpanzee's genitalia during rear mount sexual behavior.
There have been reports of elevated plasma epinephrine and norepi-nephrine levels in individuals with pedophilia (121,122). Whether such abnormalities are related to underlying anxiety disorders rather than specific to pedophilia has not been discerned.
A recent well-designed large-scale study comparing the brain functioning of men with pedophilia to men with other atypical sexual interests or behaviors found significant correlation between pedophilia and poorer than average brain functioning, as measured by Full-Scale IQ and verbal and visuospatial memory (123). The study also found a significant association between pedophilia and lower rates of right-handedness, consistent with earlier reports of decreased right-handedness in child sex offenders (124). The study's findings suggest that early (prebirth) neurodevelopmental perturbations of the developing brain may account for some cases of pedophilia. Future studies may clarify what parts of the brain are affected, whether such perturbations reflect an independent pathological process or a general risk factor, and whether such findings have relevance to the development of other paraphilias.
In another recent study, an association was identified between pedophilia and retrospectively recalled childhood accidents resulting in unconsciousness (125,126). Twice as many pedophiles as nonpedophiles reported head injuries with unconsciousness before the age of 6, suggesting that neurodevelopmental perturbations occurring in a window of time after birth may also increase the risk of pedophilia. The authors of these studies cautiously point out that more data are needed before the findings can be interpreted with confidence. Whether head injury causes a neurodevelopmental abnormality that increases the risk of pedophilia or whether a pre-existing neurodevelopmental problem increases the risk of both head injury and pedophilia is unknown.
Although most studies regarding possible etiological associations between childhood head injury and the paraphilias have focused on pedophilia, some single case studies have been cited suggesting that some fetishistic behavior may also be related to childhood head injury (127).
A study of 477 adult males with traumatic brain injury identified 27 men, or almost 6% of the sample, who, with no prior histories of sexual offending, committed sexual offenses following their head injuries (128). Some but not all of the offending behaviors were paraphilic in nature. The authors concluded that traumatic brain injury was a significant etiological factor underlying the offending behaviors. Such studies support the hypothesis that head injury is related to the development of some adult onset cases of paraphilia.
Left temporal lobe lesions have been known to result in sexual disinhibition and compulsivity in some individuals. Similarly, is evidence that temporal lobe epilepsy may cause some cases of fetishism and other paraphilias, most commonly exhibitionism (104,129). However, the majority of individuals with temporal lobe epilepsy do not have a paraphilia and, in fact, many are hyposexual. Future studies may explain the occurrence of paraphilia in a small subgroup of these individuals.
Although there is little evidence currently of a genetic link in the development of paraphilias, studies have found an association between pedophilia and Klinefelter's syndrome, a rare chromosomal variant in men (130-132).
Kafka has suggested that serotonergic factors may provide a biologic explanation for all paraphilias, but there is limited data to confirm this (133). There are also reports of fetishistic cross-dressing across generations in families (134,135). Whether such behaviors indicate biologic or social modeling underpinnings remains to be demonstrated.
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