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PubMed1996

Association study of bipolar disorder with candidate genes involved in catecholamine neurotransmission: DRD2, DRD3, DAT1, and TH genes.

Despite strong evidence for genetic involvement in the etiology of affective disorders (from twin adoption and family studies), linkage and association methodologies are still exploring the nature of genetic factors in these diseases. Interesting testable hypotheses have been described, including candidate genes involved in catecholamine neurotransmission. We studied 69 bipolar patients and 69 matched controls (for age, sex, and geographical origin) for association and linkage disequilibrium with DNA markers at the following genes: the tyrosine hydroxylase gene, dopamine transporter gene, and dopamine D2 and D3 receptor genes. Association and linkage disequilibrium were excluded between bipolar affective disorder and these four candidate genes in our sample.

Adult↗
PubMed2004

Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF: a family based association study.

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.

Alleles↗
PubMed1994

Mismatch PCR RFLP detection of DRD2 Ser311Cys polymorphism and schizophrenia.

We tested 100 schizophrenics and 100 controls to find association at the Serine311 Cysteine polymorphism of dopamine D2 receptor in Japanese population. There were no significant differences between the two groups. One homozygote for Cys311 was confirmed in the controls by mismatch-polymerase chain reaction and restriction fragment length of polymorphism (PCR-RFLP) analysis. None with Cys was detected among 61 individuals of nine multiply affected families with schizophrenia. Our data thus provide strong evidence against an etiological association between schizophrenia and the Ser311Cys variant. The polymerase chain reaction amplification of specific alleles (PASA) analysis was compared with the mismatch PCR-RFLP typing, revealing that the latter is more reliable than the former.

Alleles↗
PubMed1998

Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high risk for alcoholism.

BACKGROUND: There is evidence that both reduction in P300 amplitude and the presence of the A1 allele are risk markers for alcoholism. We hypothesized that demonstration of a relationship between the marker and the trait in young children who had not begun to drink regularly would provide evidence for dopaminergic mediation of the reduction in P300 often seen among high-risk children. A previous association between the A1 and the P300 amplitude in screened controls supports the hypothesis that this association occurs in the general population. METHODS: Children were assessed using both visual and auditory paradigms to elicit event-related potentials (ERPs). The P300 component of the ERP was investigated with respect to the genetic variation of the Taq1A D2 receptor in these children. RESULTS: Genetic association between a marker locus (Taq1 A RFLP near the D2 receptor locus) and the amplitude of P300 was found to be present in 58 high-risk children and their relatives (a total of 100 high-risk individuals). CONCLUSIONS: A higher proportion of children from alcoholic families may exhibit lower P300 because more of these children carry the A1 allele than is seen in the normal population.

Acoustic Stimulation↗
PubMed1995

Exclusion of linkage of schizophrenia to the gene for the dopamine D2 receptor (DRD2) and chromosome 11q translocation sites.

There have been previous reports of a 1q43;11q21 translocation cosegregating with schizophrenia and a 9p22;11q22.3 translocation cosegregating with manic depression. In addition, the genes for the dopamine D2 receptor and for tyrosinase both map to chromosome 11q. Three 11q DNA markers were used to investigate 23 pedigrees containing multiple cases of schizophrenia. Strongly negative lod scores were obtained, providing evidence against linkage over a 70 cM region which included both translocation sites and both candidate genes.

Chromosome Mapping↗
PubMed1997

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder). This is the first study supporting a strong association between the dopamine D2 receptor Taq A1 allele with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT1) gene with SAB was similarly found.

Adult↗
PubMed2004

Effects of quitting smoking on EEG activation and attention last for more than 31 days and are more severe with stress, dependence, DRD2 A1 allele, and depressive traits.

Changes in physiology and attentional performance associated with smoking abstinence were characterized in 67 female smokers during low-stress and high-stress conditions. Abstinence was associated with decreases in cognitive performance, heart rate, and electroencephalographic (EEG) activation but with no change in serum estradiol or progesterone. Effects of quitting showed no tendency to resolve across the 31 days of abstinence. EEG deactivation and heart rate slowing were greater during a math task (high stress) than during relaxation (low stress). Individuals high in trait depression or nicotine dependence or with at least one dopamine D(2) receptor A1 allele experienced greater EEG deactivation following abstinence, especially in the right hemisphere during the stressful task. Thus, findings support the situation x trait adaptive response model of abstinence effects and emphasize the value of multiple dependent measures when characterizing abstinence responses.

Adolescent↗
PubMed1997

D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele.

The relationship between a dopamine D2 receptor genetic polymorphism at the Taq1 A locus and the level of D2 receptor binding was investigated in normal, middle aged to elderly subjects with no psychiatric or neurological disorders. D2 receptor binding was measured by autoradiography in the caudate, putamen and nucleus accumbens, using the specific D2 receptor ligand [3H]-raclopride. In a sample of 44 individuals, only one was homozygous for the A1 allele, 25 were homozygous for A2 and 18 were heterozygotes. The presence of one or two A1 alleles was associated with reduced D2 receptor binding in all areas of the striatum, reaching statistical significance in the ventral caudate and putamen (p = 0.01 and p = 0.044, respectively). This reduction was more marked in males than females, particularly in the putamen. A genetic predisposition to lower D2 receptor expression may increase susceptibility to neuroleptic medication or clinical symptoms that are associated with diseases involving dopaminergic pathology.

Aged↗