Role of genetic factors in human sexual behavior based on studies of tourette syndrome and ADHD probands and their relatives

Comings, David E.

doi:10.1002/ajmg.1320540309

Cited by 42 publications

(26 citation statements)

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“…37,40,53 Tourette syndrome (TS) and ADHD are related, hereditary impulse disorders that are also associated with a wide range of externalizing, risk-taking, aggressive 33 Behavioral scores Each TS control and TS proband or relative was required to fill out a questionnaire based and hypersexual behaviors, 34 substance abuse, 35,36 and other behaviors. 37,38 To determine if genetic variants at on the Diagnostic Interview Schedule 54 or DSM-III-R 55 criteria.…”

Section: Introductionmentioning

confidence: 99%

“…40 Since a simple comparison of the frequency of the different behavioral scores have been described in detail elsewhere. [33][34][35]37,40,54,56 Two behavioral scores were used alleles in controls vs TS probands might miss the possibility that the MAO genes were only associated with a to assess ADHD. The first, called ADHD, was based on the presence of at least half of a series of 22 ADHD few specific behaviors not present in all cases, we tested for the possible role of these genes in 27 different variables from DSM-III and DSM-III-R criteria.…”

Section: Introductionmentioning

confidence: 99%

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Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse

et al. 1998

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Abnormalities in monoamine oxidase (MAO) levels have been implicated in a wide range of psychiatric disorders. We have examined a VNTR polymorphism at the X-linked MAOA gene to test two hypotheses: (1) Do variants of the MAOA gene play a role in any of the behavioral disorders associated with Tourette syndrome or drug abuse? (2) If so, is there any correlation between the length of the alleles and the phenotypic effect? We examined two independent groups: 375 TS patients, relatives and controls, and 280 substance abusers and controls. The alleles were divided into four groups of increasing size. There was a significant association between the MAOA gene and behavioral phenotypes in both groups, and in both the longest alleles were associated with the greatest phenotypic effect. The strongest effect was for the diagnosis of drug dependence (P = 0.00003). The VNTR allele groups were in significant linkage disequilibrium with the Fnu4H1 polymorphism previously shown to be associated with MAO-A activity. While these results are consistent with the possibility that different-sized alleles of the short-repeat polymorphisms themselves may play a role in gene regulation, further studies directly linking these alleles with enzyme levels need to be done.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse

et al. 1998

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“…The questions between the D 1 and D 2 receptors in a wide range of behaviors including schizophrenia, cataplexy, subused for these behavioral scores have been described in detail elsewhere. 32,35,37,[39][40][41]43 The rationale for stance abuse, and other behaviors. [24][25][26][27][28][29] These reports in conjunction with the results of Self et al 22 suggest the examining comorbid behaviors is the prior observation that certain genes may be more strongly associated need to test several hypotheses: 1) Are genetic variants of the DRD1 gene associated with susceptibility to with some of the comorbid behaviors present in TS than with the diagnosis per se.…”

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confidence: 99%

“…The alco-(alcohol and drug abuse, pathological gambling, sexual behaviors, compulsive eating, and others) in this hol score consisted of the summation of 'no' or 'yes' answers to 18 questions derived from the MAST test group. [32][33][34][35][36][37] for alcohol use. 33,38 The drug score was based on 'no' or 'yes' answers to nine questions based on the Diagnostic Methods…”

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confidence: 99%

Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors

et al. 1997

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Abnormalities in the dopaminergic reward pathways have frequently been implicated in substance abuse and addictive behaviors. Recent studies by Self and coworkers have suggested an important interaction between the dopamine D 1 and D 2 receptors in cocaine abuse. To test the hypothesis that the DRD1 gene might play a role in addictive behaviors we examined the alleles of the Dde I polymorphism in three independent groups of subjects with varying types of compulsive, addictive behaviors -Tourette syndrome probands, smokers and pathological gamblers. In all three groups there was a significant increase in the frequency of homozygosity for the DRD1 Dde I 1 or 2 alleles in subjects with addictive behaviors. The DRD1 11 or 22 genotype was present in 41.3% of 63 controls and 57.3% of 227 TS probands (P = 0.024). When 23 quantitative traits were examined by ANOVA those carrying the 11 genotype consistently had the highest scores. Based on these results, we examined the prevalence of the 11 genotype in controls, TS probands without a specific behavior, and TS probands with a specific behavior. There was a progressive, linear increase, significant at ␣ Յ 0.005 for scores for gambling, alcohol use and compulsive shopping. Problems with three additional behaviors, drug use, compulsive eating and smoking were significant at ␣ Յ 0.05. All six variables were related to addictive behaviors. In a totally separate group of controls and individuals attending a smoking cessation clinic, and smoking at least one pack per day, 39.3% of the controls versus 66.1% of the smokers carried the 11 or 22 genotype (P = 0.0002). In a third independent group of pathological gamblers, 55.8% carried the 11 or 22 genotype (P = 0.009 vs the combined controls). In the TS group and smokers there was a significant additive effect of the DRD1 and DRD2 genes. The results for both the DRD1 and DRD2 genes, which have opposing effects on cyclic AMP, were consistent with negative and positive heterosis, respectively. These results support a role for genetic variants of the DRD1 gene in some addictive behaviors, and an interaction of genetic variants at the DRD1 and DRD2 genes.

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“…It is not uncommon for patients with Tourette's to display obsessive-compulsive tendencies including sexual obsessions (James, 1995;Mack et al, 2010). Furthermore, Comings (1994) reported that individuals with Tourette's show deviant sexual behaviors (paraphilias) in some cases including magnitude of sex drive, sex orientation, exhibitionism, transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism, aversion to being touched, and aversion to sex. Accordingly (Comings, 1994), there was a significant positive correlation between each behavior examined and the degree of genetic loading for the Tourette's gene(s).…”

Section: Objectivesmentioning

confidence: 99%

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

McLaughlin

Oscar‐Berman²,

Simpatico³

et al. 2013

Journal of Behavioral Addictions

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Background and aims:Many patients presenting multiple behaviors including drug and food abuse as well as other pathological repetitive unwanted activities such as gambling, self-mutilation and paraphilias may not be appropriately diagnosed. Here we present a case of a male presenting many of these seemingly diverse behaviors and finally diagnosed with reward deficiency syndrome (RDS) by his attending physician. Methods: The use of the dopamine agonist, ropinirole after two weeks showed improvement in terms of sexual behavior but tolerance set in and was discontinued especially when an infraction occurred with the patient's insurance. In this article, we carefully explore the potential of ropinirole to downregulate dopamine receptors causing adenylate cyclase receptor supersensitivity and tolerance a feature of neurotransmitter cross-talk. Based on previous scientific evidence showing KB220Z-nutrigenomic amino-acid therapy (NAAT) to rapidly (post one-hour) activate dopaminergic pathways in both the pre-frontal cortex cingulate gyrus (relapse loci) and ventral tegmental area-caudate-accumbens-putamen (craving and emotion loci) the patient was prescribed NAAT. Results and discussion: Within one week of utilization the repetitive paraphilia was eliminated. There were also a number of other positive effects such as enhanced focus that persisted even after the patient stopped using KB220Z suggesting neuroplasticity (e.g. altruistic thoughts). However, these observed profound benefits require more in-depth study, especially in a large cohort against a placebo. While this report focused on a rapid response rather than long-term benefits previously associated with NAAT, it is somewhat encouraging and longer term required follow-up and larger placebo controlled studies are warranted before any definitive conclusions could be gleaned from this case report.

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Role of genetic factors in human sexual behavior based on studies of tourette syndrome and ADHD probands and their relatives

Cited by 42 publications

References 68 publications

Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse

Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse

Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

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