Objective
The brain reward circuits that promote drug abuse may also be involved in pleasure seeking behavior and food cravings observed in severely obese subjects. Drug addiction polymorphisms such ...as the TaqI A1 allele of the dopamine D2 receptor (DRD2) are associated with cocaine, alcohol, and opioid use, but few studies have linked DRD2 to food craving. Other genes such as the leptin receptor gene (LEPR) and mu‐opioid receptor gene (OPRM1) that affect appetite and pleasure centers in the brain may also influence food addiction and obesity. The three genes together may function synergistically.
Design and Methods
To evaluate associations between candidate genes, food craving, overeating, and BMI, we administered questionnaires including Power of Food Scale and Food Craving Inventory, conducted anthropometric measures, and collected blood from patients undergoing weight‐loss treatment. Questionnaires and DNA specimens were collected for 80 participants.
Results
Participants were mostly female (74%) and Caucasian (79%), with an average age of 53 years old. Mean BMI for all participants was 43 kg/m2 and was significantly associated in a linear fashion with Food Craving Inventory scores (P=0.0001) and Power of Food (P=0.02). The DRD2 TaqI A1 allele was significantly associated with BMI (P=0.04), while LEPR Lys109Arg and OPRM1 A118G variants were not. We stratified DRD2 by LEPR and OPRM1, and observed a significant interaction (P = 0.04) between DRD2 and LEPR, and a marginally significant interaction (P=0.06) between DRD2 and OPRM1.
Conclusion
Genes associated with addictive behavior and appetite control may therefore, in combination, markedly influence development of clinically severe obesity.
Association of alleles at the Taq1 A, Taq1 B, intron 6, Taq1 D, exon 7, exon 8, and promoter-141C sites of the D2 dopamine receptor gene with D2 dopamine receptor binding characteristics in the ...caudate nucleus of Caucasian alcoholic and nonalcoholic subjects was determined. For the Taq1 D, exon 7, exon 8, and promoter- 141C sites there were no significant allelic differences in Bmax (number of binding sites) or Kd (binding affinity) of the D2 dopamine receptors. However, subjects having the minor alleles at the Taq1 A, Taq1 B, and intron 6 sites had significantly lower Bmax than subjects not having them. None of these three polymorphisms had any significant effect on Kd. Highly significant linkage disequilibria were observed among the Taq1 A, Taq1 B, and intron 6 polymorphic sites, but linkage disequilibria between these three sites and each of the Taq1 D, exon 7, exon 8, and promoter-141C sites were of lesser or of no significance. Taken together, these findings suggest that the Taq1 A, Taq1 B, and intron 6 polymorphisms, but not the Taq1 D, exon 7, exon 8, and promoter-141C polymorphisms, are in linkage disequilibrium with a functional allelic variant that affects D2 dopamine receptor expression.
Abstract During adolescence there is a significant increase in risk-taking behavior, including experimenting with alcohol and drugs, which can lead to drug dependence. A new hypothesis regarding the ...genetic mechanisms that lead to drug use is tested using adolescent Caucasian children of alcoholics (57 males, 54 females; mean age = 14.5 years) data. Variables included in the study were dopaminergic genes (ANKK1 TaqI A, DRD2 C957T, DRD4 7R, COMT Val/Met substitution, and SLC6A3 9R) and a GABAergic gene (GABRB3), all combinations of genes, a count of the number of hypodopaminergic genotypes, personality traits, neurocognitive factors, depressive symptoms, and environmental factors. Separate predictive models were found for males and females. Hypodopaminergic functioning predicted drug use in males; however, in females, a deleterious environment was the salient predictor. This preliminary study suggests that it is possible to identify children at risk for problematic drug use prior to the onset of drug dependence.
Abstract Objective To examine the potential contribution of the serotonin hydroxylase (TPH1 and TPH2) genes, and the serotonin transporter promoter polymorphism (5HTTLPR) to the unique and ...pleiotropic risk of PTSD symptoms and depressive symptoms. Methods Participants included 200 adults exposed to the 1988 Spitak earthquake from 12 multigenerational families (3 to 5 generations). Severity of trauma exposure, PTSD, and depressive symptoms were assessed using standard psychometric instruments. Pedigree-based variance component analysis was used to assess the association between select genes and the phenotypes. Results After adjusting for age, sex, exposure and environmental variables, there was a significant association of PTSD symptoms with the ‘t’ allele of TPH1 SNP rs2108977 (p < 0.004), explaining 3% of the phenotypic variance. This allele also showed a non-significant trend for an association with depressive symptoms (p = 0.08). Also, there was a significant association of PTSD symptoms and the ‘t’ allele of TPH2 SNP rs11178997 (p = 0.03), explaining 4% of the variance. Depressive symptoms were significantly associated with the ‘s’ allele of 5HTTLPR (p = 0.03), explaining 4% of the variance. Limitations Retrospective rating of exposure may have been subject to memory failure leading to misestimation of symptom severities. Second, findings may not be generalizable to other ethnic/racial populations. Conclusion To our knowledge, this is the first published report showing that variants in TPH1 and TPH2 genes constitute risk factors for PTSD symptoms. Additionally, the TPH1 gene may be associated pleiotropically with PTSD and depressive symptoms. The association of the ‘s’ allele of 5HTTLPR polymorphism with depression adds to similar findings from case/case–control studies.
Reuter, Roth, Holve, & Hennig (2006) described what they called the first candidate gene for creativity. This study replicated and extended their work for a more careful analysis of five candidate ...genes: Dopamine Transporter (DAT), Catechol-O-Methyltransferase (COMT), Dopamine Receptor D4 (DRD4), D2 Dopamine Receptor (DRD2), and Tryptophane Hydroxylase (TPH1). Participants were 147 college students who received a battery of tests of creative potential. Multivariate analyses of variance indicated that ideational fluency scores were significantly associated with several genes (DAT, COMT, DRD4, and TPH1). This was apparent in both verbal and figural fluency ideation scores, before and after controlling general intelligence. Yet fluency, alone, is not an adequate measure of creativity, and the index that is by far the most important part of creativity (i.e., originality) had a negligible relationship with the genes under investigation. Hence, in contrast to earlier research, the conclusion offered here is that there is a clear genetic basis for ideational fluency, but that fluency, alone, is not sufficient to predict or guarantee creative performance. Hence, at present, the genetic basis of creativity remains uncertain.
Highlights • 1146 genes are differentially expressed in schizophrenia. • A strong pattern of differentially expressed immune response genes. • 23 genes are clinically proven drug targets as well as ...20 antipsychotic agents. • 16 genes are associated with schizophrenia from the Psychiatric Genomics Consortium.
Abstract Background Dopaminergic and serotonergic systems have been implicated in PTSD. The present study evaluated the association of four catechol-O-methyltransferase ( COMT ) gene loci, and the ...joint effect of COMT and tryptophan hydroxylase 2 ( TPH 2) genes on PTSD symptoms. Methods Subjects included 200 Caucasian Armenian adults exposed to the 1988 Spitak earthquake from 12 multigenerational (3–5 generations) families. Instruments used included the UCLA PTSD Reaction Index based on DSM-5 criteria, and the Beck Depression Inventory. Results The adjusted heritabilitiy of vulnerability to DSM-5 based PTSD symptoms was 0.60 ( p <10−4 ). There was a significant association of the COMT allele rs4633C with total PTSD ( p <0.03), and D category (p<0.04) (negative alterations in cognitions and mood) severity scores, but not with C category (avoidance) scores. There was no genetic correlation between C and D category severity scores. COMT allele rs4633C and the TPH-2 allele rs11178997T together accounted for 7% of the variance in PTSD severity scores ( p <0.001). None of the COMT alleles were associated with depression. Limitations The ratings of earthquake exposure and prior trauma may have been subject to recall bias. The findings may not be generalizable to other ethnic/racial populations. Conclusion COMT allele rs4633C may be causally related and/or is in linkage disequilibrium with gene(s) that are causally related to PTSD symptoms. Carriers of these COMT and the TPH-2 alleles may be at increased risk for PTSD. The findings provide biological support for dividing DSM-IV category C symptoms into DSM-5 categories C and D.
Objective:
Type 2 diabetes is commonly found in schizophrenia and is an important contributor to mortality and morbidity in this condition. Dopamine has been implicated in the aetiology of both ...diabetes and schizophrenia. It is possible that both disorders share a common genetic susceptibility.
Methods:
In a cross-sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia. All participants met DSM-IV criteria for schizophrenia, and those with other psychiatric disorders were excluded. Analysis of covariance was used to compare fasting glucose results by DRD2 genotypes, after controlling for known confounds. For significant associations, follow-up Bonferroni post hoc tests examined differences in fasting glucose levels between genotypes. Specific comparisons were also made using analysis of variance and chi-square (Fisher’s exact test).
Results:
The 2 DRD2 risk genotypes were associated with significant increases in blood glucose, after controlling for BMI, age, sex, dosage and type of antipsychotic medication, number of hospitalisations, and negative symptoms (rs6275, F(2, 182) = 5.901, P = 0.003; rs6277 SNP, F(2, 178) = 3.483, P = 0.033).
Conclusions:
These findings support the involvement of DRD2 not only in schizophrenia but also in elevated levels of blood glucose commonly found in antipsychotic-treated patients with schizophrenia. Our data support the notion that diabetes may not merely be a comorbid condition but could be fundamentally associated with the pathogenesis of schizophrenia itself.
Alexithymia is characterized by difficulty identifying feelings, difficulty describing feelings, and an externally oriented thinking style. Alexithymia has been described as a trait-like risk factor ...for the development of alcohol use disorders. Few studies have investigated the absolute (whether mean scores change over time) and relative (extent to which relative differences among individuals remain the same over time) stability of alexithymia among men and women with alcohol dependence, or have considered potential underlying mechanisms. Social learning processes contribute to and maintain alcohol problems. The reinforcement of alcohol expectancies is one plausible mechanism that links the difficulties in emotional processing associated with alexithymia and alcohol use. The present study investigated the stability of alexithymia as well as alcohol expectancy as a mediator of alexithymia. Three hundred fifty-five alcohol-dependent patients were enrolled in a cognitive behavioral treatment program. Ninety-two alcohol-dependent patients completed assessments at baseline and at 3-month follow-up. Results indicated that total Toronto Alexithymia Scale (TAS-20; Bagby, Parker, & Taylor, 1994) mean score, difficulty identifying feelings, and difficulty describing feelings decreased significantly over time with a larger decrease in alexithymia mean scores for females. Externally oriented thinking mean scores did not change. The TAS-20 and its subfactors demonstrated significant correlations, from baseline to follow-up, which were stronger for males than for females. Regression analyses showed that the total TAS-20 mean scores, difficulty identifying feelings, and difficulty describing feelings were partially mediated through assertion alcohol expectancies. In conclusion, this suggests that alexithymia has relative stability and is a trait-like factor among alcohol-dependent treatment seekers.
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