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Biomedical subjects

D E Comings

Publications and source records attributed to D E Comings.

At least 73 records · Page 4Linked to original sources
PubMed1995

Dopamine D2 receptor gene (DRD2) haplotypes and the defense style questionnaire in substance abuse, Tourette syndrome, and controls.

The defence style questionnaire (DSQ) was administered to Caucasian males consisting of 123 subjects from a V.A. addiction treatment unit (ATU), 42 Tourette syndrome (TS) subjects, and 49 controls. For the ATU and TS subjects, there was a significant decrease in the mean score for mature defenses and a significant increase in mean score for immature defenses compared to controls. Many of the individual subscores showed the same significant differences. Dopamine D2 receptor (DRD2) gene haplotypes, identified by allele specific polymerase chain reaction of two mutations (G/T and C/T) 241 base pairs apart, were determined in 57 of the ATU subjects and 42 of the controls. Subjects with the 1 haplotype tended to show a decrease in mature and an increase in neurotic and immature defense styles compared to those without the 1 haplotype. Of the eight times that the subscale scores were significant for haplotype 1 versus non-1, they were always in this direction. There results suggest that the DRD2 locus is one factors controlling defense styles. The difference in the mean scores between controls and substance abuse subjects indicates that other genes and environmental factors also play a role.

Alcoholism↗
PubMed1995

Role of genetic factors in depression based on studies of Tourette syndrome and ADHD probands and their relatives.

Tourette syndrome (TS) is a common, neuropsychiatric disorder which has many similarities to attention deficit hyperactivity disorder (ADHD). TS probands have a high frequency of a variety of behavioral disorders including depression. The depression may be due to a pleiotrophic effect of the Gts genes, proband ascertainment bias, or a result of coping with the chronic tics. To distinguish between these hypotheses we examined the responses to 17 Diagnostic Interview Schedule questions to evaluate the 9 DSM-III-R criteria for major depressive episode in 1,080 adults consisting of TS and ADHD probands, their relatives and controls. Using a Bonferonni corrected p there was a significant progressive increase in 16 of 17 depressive symptoms and for a life time history of a major depressive episode in groups with increased genetic loading for Gts genes. Similar trends were seen in the small number of ADHD probands and their relatives. There was also a significant increase for these variables in non-proband TS relatives versus non-TS relatives, indicating the association of depression with Gts genes was not due to ascertainment bias or the inappropriate choice of controls. Multiple linear regression analysis indicated that obsessive-compulsive behaviors, sex, ADHD, drug abuse, and age all showed a more significant effect on depressive symptoms than the number of tics. The presence or absence of TS in the relatives had a much greater effect on risk for depression than the presence or absence of an episode of major depression in the proband. These results are consistent with the hypothesis that Gts and ADHD genes play a major role in depression.

Adolescent↗
PubMed1995

A dopamine D3 receptor genotype is associated with hyperandrogenic chronic anovulation and resistant to ovulation induction with clomiphene citrate in female Hispanics.

OBJECTIVE: To determine if dopamine (D3) receptor genotypes are associated with anovulation and response to ovulation induction with clomiphene citrate. DESIGN: Clinical and laboratory characteristics of anovulatory patients and ovulatory controls were compared with findings at the DNA level. SETTING: An outpatient clinic at an university medical center. PATIENTS: One hundred eighty human Hispanic female volunteers (130 of these with documented ovulatory status) were studied. INTERVENTIONS: Genomic DNAs were extracted from each patient. Polymerase chain reaction with subsequent restriction digest was performed to analyze the D3 receptor allele status (two possible alleles). MAIN OUTCOME MEASURES: Menstrual history, serum T, and midluteal serum Ps from spontaneous and clomiphene cycles were correlated with D3 receptor genotype. RESULTS: Hispanic females with the 22 genotype compared with the other genotypes (11 and 12) were more likely to have irregular menses, an elevated serum T (> or = 70 ng/dL [conversion factor to SI unit, 3.467]), and hyperandrogenic chronic anovulation. These patients tended to be resistant to ovulation induction requiring a significantly higher dose of clomiphene to achieve an ovulatory response (22 genotype [mean +/- SEM] [140.0 +/- 19.0 mg] versus 11 [77.1 +/- 17.5 mg] or 12 [69.2 +/- 13.1 mg]). This effect was independent of patient age, weight, or serum T level. CONCLUSIONS: Hyperandrogenic chronic anovulation may have a genetic component. Genetic analysis may be useful in predicting resistance to ovulation induction with clomiphene.

Alleles↗
PubMed1995

Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour.

Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.

Behavior, Addictive↗
PubMed1995

The role of genetic factors in conduct disorder based on studies of Tourette syndrome and attention-deficit hyperactivity disorder probands and their relatives.

To examine the role of genetic factors in oppositional defiant disorder (ODD) and conduct disorder (CD), 38 variables relating to the relevant DSM-III-R criteria, as well as other angry and aggressive behaviors, were examined in 1177 Tourette syndrome (TS) and attention-deficit hyperactivity disorder (ADHD) probands, their first-degree relatives, and controls. Two techniques were used: (1) a genetic loading technique comparing the frequency of symptoms in groups with progressively less genetic loading for Gts and ADHD genes, and (2) comparison of the frequency of symptoms in relatives with, versus relatives without, TS or ADHD. When significant, the latter rules out ascertainment bias and inappropriate controls. For TS, the results were significant with most p values less than 10(-8). The same trends were seen in the smaller number of ADHD families. A polygenic model is proposed in which TS and ADHD alone represent lesser degrees of genetic loading and expression, and TS + CD not equal to ADHD represents a higher degree of genetic loading and expression of genes common to all three disorders. These studies emphasize the important role of genetic factors in ODD and CD. The therapeutic implications are discussed.

Adolescent↗
PubMed1995

Tourette's syndrome: a behavioral spectrum disorder.

Tourette's syndrome is a fascinating, complex, hereditary, neuropsychiatric spectrum disorder in which the tics are only one of many symptoms. Data to date suggest the mechanism of inheritance is just as complex as the disorder itself and involves the coming together of a number of common genes that affect dopamine and serotonin metabolism. Because these neurotransmitters modulate the function of many areas of the brain, the result is a wide spectrum of behavioral disorders. As such TS provides a significant challenge to the physician. Because many of the newer medications are quite effective, taking on the treatment of this challenging and complex behavioral spectrum disorder can be extremely rewarding.

Attention Deficit Disorder with Hyperactivity↗
PubMed1994

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

Most significant variations in the expression of human sexuality are considered to be the result of learned behavior or psychological problems. Tourette syndrome (TS) is a common, hereditary tic and disinhibition disorder sometimes associated with compulsive use of obscene words (coprolalia) and previously reported to be occasionally associated with exhibitionism. To further explore the relationship between the Gts genes and sexual behavior, questions concerning a wide range of such behaviors were administered to 1,040 subjects, 14 years of age or older, consisting of 358 TS probands, 101 non-proband relatives with TS, 359 non-TS first degree relatives, 79 attention deficit hyperactivity disorder (ADHD) probands, 70 unaffected relatives of the ADHD probands, and 73 controls. The behaviors included magnitude of sex drive, sex orientation, exhibitionism, transvestitism, transsexualism, sadism, masochism, pedophilia, fetishism, aversion to being touched, and aversion to sex. While most of these behaviors occurred in a distinct minority of TS subjects, there was a significant positive correlation between each behavior examined and the degree of genetic loading for the Gts gene(s). The nature of these behaviors and their association with TS suggests many are variants of obsessive-compulsive disorder. Studies in animals indicate that changes in serotonin and dopamine play a significant role in the sexual behavior and many lines of evidence are consistent with the hypothesis that TS is due to genetic changes in serotonin and dopamine metabolism. These studies suggest that genetic factors play a much greater role in a wide range of forms of sexual expression than previously thought.

Adolescent↗
PubMed1994

Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. I. Drug abuse.

There have been relatively few studies of genetic factors in drug abuse. Childhood Attention Deficit Hyperactivity Disorder (ADHD) has been implicated as a risk factor, and pedigree studies of Tourette Syndrome (TS), a hereditary impulse disorder closely related to ADHD, show an increased prevalence of substance abuse in relatives. These observations suggest the genes for TS and ADHD may play an important role in the development of drug abuse. To examine this hypothesis 217 TS probands and 328 of their relatives, 58 ADHD probands and 35 of their relatives, and 50 controls were prospectively studied using a structured questionnaire based on the Diagnostic Interview Schedule. All subjects were Caucasians 16 to 49 years of age. The responses concerning the use of 8 different drugs and 8 different symptoms of drug abuse were compared. The results showed a highly significant increase in positive responses with increased loading for the TS and ADHD genes for 6 of the 8 drugs and all of the drug abuse symptoms. The percentage of positive responses in TS probands was markedly influenced by the presence of comorbid ADHD, as well as discipline, obsessive-compulsive, or alcohol problems. These results suggest that the genes responsible for TS and ADHD play an important role in drug abuse/dependence. The dopamine D2 receptor gene (DRD2) appears to be one of these genes since variants at this locus are significantly increased in frequency in TS, ADHD, conduct disorder and drug abuse.

Adolescent↗
PubMed1994

Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. II. Alcohol abuse.

Prior studies have suggested childhood attention deficit hyperactivity disorder (ADHD) as a risk factor for alcohol abuse in adults. Gilles de la Tourette Syndrome, a hereditary tic and impulse disorder, is clinically and genetically similar to ADHD. To examine the hypothesis that individuals carrying the Gts gene are at increased risk to develop alcohol use problems, the same TS (Tourette Syndrome) and ADHD probands, relatives and controls used in the prior study of drug abuse were also studied using a structured questionnaire based on the Diagnostic Interview Schedule and the MAST test. The frequency of a positive response to any of 16 different questions concerning alcohol abuse showed a highly significant increase with increased genetic loading for Gts and ADHD genes. The percentage of more than one positive response in TS probands was markedly influenced by the presence of comorbid ADHD, discipline, obsessive-compulsive or drug abuse problems. Comorbid drug abuse problems were the best predictor of alcohol abuse problems. These results suggest that the genes responsible for TS and ADHD play an important role in alcohol abuse/dependence as well as drug abuse/dependence. One of the elements common to all of these disorders may be mutant genes affecting serotonin metabolism.

Adolescent↗
PubMed1994

The dopamine D2 receptor gene: a genetic risk factor in substance abuse.

Drug abuse has grown to epidemic proportions. Dopaminergic reward pathways have frequently been implicated in the etiology of drug addiction. To examine the possible role of genetic variants of the dopamine D2 (DRD2) gene in susceptibility to drug abuse we determined the prevalence of the TaqI A1 variant of the DRD2 gene in 200 white patients hospitalized in the Addiction Treatment Unit of a Veterans Administration Hospital. While the prevalence of the D2A1 allele was not significantly increased over controls, it did increase from 21% in subjects with alcohol abuse only to 32% in subjects with alcohol dependence only, consistent with other studies showing an association with the severity of alcoholism. By contrast, of 104 subjects with a discharge diagnosis of drug and alcohol abuse/dependence, 42.3% carried the D2A1 allele versus 29.0% of the 763 white controls (representing all white controls published to date) (P = 0.006). Of those who spent more than $25/week on two or more substances, 56.9% carried the D2A1 allele versus 28.2% of those abusing a single substance (P < 0.0005). Multiple logistic regression analysis showed a highly significant association between multiple substance abuse based on money spent and the presence of the D2A1 allele (P = 0.0003) and age of onset of abuse (P < 0.0001). D2A1 carriers exceeded D2A2A2 subjects for a history of being expelled from school for fighting (P = 0.001), and of those ever jailed for violent crimes, 53.1% carried the D2A1 allele versus 28.8% of those jailed for non-violent crimes (P = 0.011).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Association of dopamine D2 receptor gene haplotypes with anovulation and fecundity in female Hispanics.

Dopamine is an important neurotransmitter in the hypothalamic control of gonadotrophin secretion. Neuron response is mediated through one of five different dopamine receptors. We explored the association of D2 receptor gene polymorphisms with disorders of ovulation. We utilized a multiplex allele specific polymerase chain reaction (PCR) to detect two bi-allelic polymorphisms (four potential haplotypes) in intron 5 and exon 6 of the D2 receptor gene. A second PCR/restriction endonuclease digest was utilized to verify this. Using these assays, 185 female Hispanics (51% with known ovulatory dysfunction and 49% with normal function) were haplotyped. One allele (3) was not present in the population and there were no significant differences in remaining allele distribution between ovulatory and anovulatory patients. However, significant associations were noted between alleles and gonadotrophins and fecundity. The 4 allele had a different reproductive profile compared to the 2 allele. The 4 allele was associated with significantly higher concentrations of luteinizing hormone (LH) (means +/- SE) (19.2 +/- 2.2 versus 12.3 +/- 1.3 mIU/ml, P < 0.02) and follicle stimulating hormone (FSH) (13.2 +/- 2.0 versus 10.0 +/- 0.6 mIU/ml, P < 0.05), significantly lower concentrations of prolactin (7.9 +/- 0.8 versus 14.9 +/- 3.5 ng/ml, P < 0.02) and higher parity (1.4 +/- 0.12 versus 0.92 +/- 0.13) and lower miscarriage rates (0.89 +/- 0.1 versus 1.33 +/- 0.24, P < 0.04). We conclude that D2 receptor alleles may be associated with reproductive success through altered gonadotrophin secretion and that this effect may be independent of ovulatory function.

Adult↗
PubMed1994

Tourette syndrome: a hereditary neuropsychiatric spectrum disorder.

The objective was to determine if the high frequency of behavioral problems in Tourette syndrome (TS) probands is the result of the pleiotrophic expression of the Gts genes or due to ascertainment bias. It was possible to distinguish between these two hypotheses by comparing the frequency of these behaviors in nonproband relatives with TS to relatives without TS. Twenty behavioral problems were prospectively assessed in a consecutive series of 361 TS probands, 113 nonproband TS relatives, 380 relatives without TS, and 68 controls, by the administration of a questionnaire based on the Diagnostic Interview Schedule and the DSM-III-R. Significance was set at a very conservative level of p < or = .001. Except for problems with smoking, reading and compulsive eating, all other behaviors were significantly more common in nonproband TS relatives than in relatives without TS. The relatives were also dichotomized on the basis of each of the behavioral problems. Regardless of the behavioral trait used, there was a higher frequency of all other behaviors in those who were positive versus those who were negative for that behavior. Ranking according to the number of behaviors that were significant indicated that mania, obsessive-compulsive behaviors and schizoid behaviors represented higher degrees of expression of the Gts genes than chronic tics. These results indicate that the Gts genes cause a spectrum of behavioral disorders in addition to chronic tics, indicate that TS is a behavioral spectrum disorder, and emphasize the role of genetic factors in a wide range of human behaviors.

Adolescent↗