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Neurological control of human sexual behaviour: Insights from lesion studies

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We review the human literature examining the effects of neurological insult on human sexual behaviour. We provide a synthesis of the findings to date, and identify key brain regions associated with specific aspects of human sexual behaviour. These include subcortical and cortical regions, with the mesial temporal lobe and the amygdala in particular being a crucial structure in the mediation of human sexual drive.
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... They are often diagnosed with impulse control disorders (Allnutt and Bradford, 1996;Tenbergen and Wittfoth, 2015). Since the serotonergic system has been implicated in impulse control and serotonin (5-HT) is an important neurotransmitter in the limbic system (Thompson and R Lummis, 2006), which has been associated with paraphilias (Baird and Wilson, 2007), it might play an important role in both, child sexual offending (CSO) and pedophilia. In addition there have been a number of genetic investigations of the serotonergic system in pedophilia (Mincke and Cosyns, 2006;Perrotta 2020). ...
... In our study we were mainly interested in the serotonin transporter SLC6A4 as SSRIs are also known for their sexual regulative effects (Bradford 1999), and the serotonin receptor subtype HTR3A being the only serotonin receptor subtype with modulatory function on neurotransmission, and showing particular expression in the limbic system, where paraphilias are assigned (Baird and Wilson, 2007). The cohort we used for our study ("NeMUP") has clinically been characterized in detail before (Gerwinn and Weiß, 2018): Notably, pedophile offenders (P + CSO), subjects with a pedophilic sexual preference without CSO (P-CSO) as well as child sexual offenders without pedophilia (CSO-P) had significantly higher rates of most CTQ-subscales (emotional, physical and sexual abuse and emotional neglect), in childhood and adolescence than healthy controls (HC). ...
... SLC6A4 and HTR3A in individuals with pedophilia and/or CSO, respectively, may differ from those in control subjects since the serotonergic system has previously been linked to various behavioral parameters including sexual behavior, impulse control and due to its potential involvement in sexual preference (Thompson and R Lummis, 2006) (Baird and Wilson, 2007). Epigenetic alterations (like change in methylation rates) of the serotonergic systems may reactively occur after own experienced childhood trauma. ...
Article
Numerous studies have shown associations between anomalies of the serotonergic system and impulsive behavior, depression, or traumatic life events. However, it is currently unknown, whether pedophilia or child sexual offending (CSO) is also related to alterations of the serotonergic system. Using a two by two factorial paradigm within a multisite consortium (NeMUP*) study cohort, we analyzed whether the SLC6A4-linked polymorphic region (SLC6A4LPR) or the SLC6A4 (transporter) and HTR3A (receptor) promotor methylation rates differed with regard to a pedophilic preference and/or child sexual offending. Methylation rates of HTR3A showed significant differences between child sexual offenders and non-offenders, with child sexual offenders showing lower methylation rates. Moreover, HTR3A methylation rates showed significant negative correlations with the Child Trauma Questionnaire (CTQ) subscale “sexual violence”, and the number of sexual offenses committed. Interestingly, we also found pedophilia-related alterations in 5HT3A as well as SLC6A4 methylation rates. For HTR3A we detected significant higher methylation rates in subjects with a pedophilic sexual preference, whereas for SLC6A4 methylation rates were reduced, indicating a possible downregulation of the serotonergic system in total. Although there were no significant group differences concerning the SLC6A4LPR, we found a significant correlation of the SLC6A4 methylation rate with this polymorphism in pedophilia. The present study suggests an involvement of epigenetic alterations of the serotonergic system in pedophilia and child sexual offending as well as own experience of sexual violence. While such an environmental factor may account for the epigenetic changes seen in child sexual offending, this was not seen in pedophilia. These findings will hopefully inspire further research in this underinvestigated field which should aim at validating and extending these initial results.
... 36 Other affected erection types in PSSD include psychogenic erections and, in more severe cases, we may find loss of reflexogenic erections which are mediated via a spinal reflex. 36,37 Loss of erection could be explained by reduced oxytocin in several brain regions such as the paraventricular nucleus of the hypothalamus. Administration of oxytocin into male rat brains has been found to potentiate penile erections. ...
... 60 It has also been demonstrated that stress-induced cortisol release causes an increase in glutamate release, which in turn alters neuronal plasticity, thus maintaining evoked neurological changes. 37,61 Altogether, stress or external cortisol, cause down-regulation of the pre-synaptic 5HT1A receptors, desensitization of the post-synaptic 5HT1A receptors, increases in TPH mRNA and protein levels and increases in glutamate release. Thus, in PSSD-susceptible individuals, stress may trigger maladaptive neuronal processes resulting in permanent maladaptive neurological changes. ...
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Introduction Post-SSRI sexual-dysfunction (PSSD) is an iatrogenicsyndrome, the underlying neurobiological mechanisms of which areunclear. Symptom onset follows cessation of serotonergicantidepressants i.e. Selective Serotonin and Norepinephrine ReuptakeInhibitors (SSRI's, SNRI's), and Tricyclic antidepressants (TCA's). PSSDsymptoms include genital anesthesia, erectile dysfunction andorgasmic/ejaculatory anhedonia, and should be differentiated fromdepression-related sexual-dysfunction. Recently, accumulated data of numerous case-reports suggest additional non-sexual symptoms including, anhedonia, apathy, and blunted affect. PSSD gained official recognition after the European medical agency concluded that PSSD is a medical condition that persists after discontinuation of SSRI's and SNRI's. Objective To review possible underlying neurobiological mechanisms ofthis syndrome, update information on the pathophysiology, present a listof potential risk-factors and discuss potential management options forPSSD. Methods Extensive literature review on the main symptom-patterns ofthis disorder was undertaken using PubMed. It includes introductoryexplications of relevant neurobiology with the objective of generatinghypothesis. Results Precipitating factors for PSSD include previous exposure to certain drugs, genetic predisposition, psychological stress or chemical stressful reaction to antidepressants along pre-existing medical conditions affecting neuroplasticity. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression, dopamine-serotonin interactions, serotonin neurotoxicity and hormonal changes. The diagnosis of PSSD is by excluding all other etiologies of sexual-dysfunction. Treatment is challenging, and many strategies have been suggested without definitive outcomes. We offerthe contours of a future neurobiological research agenda, and propose several underlying mechanisms for the various symptoms of PSSD which could be the foundation for a future treatment algorithm. Conclusion There is a need for well-designed neurobiological research in this domain, as well as in the prevalence, pathophysiology, and treatment of PSSD. Practitioners should be alert to the distinctive features of PSSD. Misdiagnosing this syndrome might lead to harmful Sexual Medicine Reviews. Peleg LC, Rabinovitch D, Lavie Y, et al. Post-SSRI Sexual Dysfunction (PSSD): Biological Plausibility, Symptoms, Diagnosis, and Presumed Risk Factors. Sex Med Rev 2021;XX:XXX–XXX
... Cortical structure that is involved in regulating the sexual behavior is the prefrontal cortex (PFC), specifically the orbitofrontal cortex (OFC). 1 Hypersexual behaviors involving lesions in these structures have been reported secondary to infarcts, traumatic brain injury, and postsurgical interventions. 2 Thalamus, a paired gray matter subcortical structure, is made up of a series of nuclei that are responsible for receiving different sensory signals and plays an important role in episodic memory and learning. Although thalamus is important for the reward pathway, as a part of limbic system, its role in sexual behaviors is less explored. ...
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Thalamus is a group of nuclei located deep inside the brain, well known for its sensory and cognitive functions. However, its role in the reward and behavior regulation is less explored. In this case series, we have presented four cases with inappropriate sexual behaviors (ISB) that are temporally related to thalamic infarction. We have discussed about the limbic part of thalamus and its extensive connections with other regions in regulating sexual behaviors. Although in all the four cases described there was underlying cognitive impairment that can itself increase the risk of ISB, there was potential contributing role of thalamic lesions.
... This might have been because the encephalitis was not too severe to cause edema or early treatment contributed to spare the morphological changes. From a neurological point of view, the thalamus contributes to attention control [4], and septal stimulation elicits a compulsion to masturbate [5]. These localizations were consistent with SPECT findings; thus, the patient's hyperperfusion area might have shown the inflammation with hyperstimulation to the surrounding systems. ...
... Six main regions are identified for ISB like behaviours, including three subcortical (septal region, hypothalamus and ansa lenticularis and pallidus) and three cortical regions (frontal, parietal and temporal lobes). 60 Maharshi Bhela has rightly predicted that having intact inhibitory control (Goohate Guhyam) denotes neurological as well as general health and excludes various neurological syndromes. ...
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This study's objectives were to characterize the frequency and profile of behavioral and cognitive dysexecutive syndromes in patients with focal prefrontal cortex damage and how these syndromes overlap. We also examined the contribution of the prefrontal brain regions to these syndromes. Therefore, thirty patients with prefrontal cortex damage and thirty control subjects were compared on their performances using the GREFEX battery assessing the dysexecutive syndromes. The results showed that combined behavioral and cognitive dysexecutive syndrome was observed in 53.33%, while pure cognitive dysexecutive syndrome was observed in 20% and behavioral in 26.67%. Also, almost all behavioral and cognitive dysexecutive disorders discriminated frontal patients from controls. Moreover, correlations and regression analyses between task scores in both domains of dysexecutive syndromes showed that the spectrum of behavioral disorders was differentially associated with cognitive impairment of initiation, inhibition, generation, deduction, coordination, flexibility and the planning process. Furthermore, the patterns of cognitive and behavioral dysexecutive syndrome were both predictors of impairment in daily living activities and loss of autonomy. Finally, frontal regions contributing to different dysexecutive syndromes assessed by MRI voxel lesion symptom analysis indicate several overlapping regions centered on the ventromedial and dorsomedial prefrontal cortex for both domains of dysexecutive syndrome. This study concludes that damage to the frontal structures may lead to a diverse set of changes in both cognitive and behavioral domains which both contribute to loss of autonomy. The association of the ventromedial and dorsomedial prefrontal regions to both domains of dysexecutive syndrome suggests a higher integrative role of these regions in processing cognition and behavior.
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THE ASSOCIATION of male sexual deviation with temporal lobe epilepsy has been noted in a considerable number of cases described in the literature.1-8 The inference that the temporal lobe lesion plays a causative role in the development of sexual deviations seemed warranted, especially in the case presented by Mitchell et al,6 but there was no evidence against the possibility that these cases of association of temporal lobe lesion and sexual deviation are only a matter of chance. Since sexual deviation is viewed as a developmental disorder, it was hypothesized that for a brain lesion to have etiological significance, for its development it would need to have been present since early childhood.9-12 Because of the reported association of sexual deviation and temporal lobe lesion, it was predicted that in a sample of subjects with various brain lesions the sexual deviations will predominantly be associated with temporal lobe lesions lasting since early infancy.
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The hypothalamo-hypophyseo-gonadal axis has been generally looked upon as the neuroendocrine basis of sexual behavior and many animal studies support this view. Higher neuronal circuits must be involved in sexuality, at least in man, but there has been little curiosity and little knowledge concerning these mechanisms.