"Like parent, like child": Attention deficit hyperactivity disorder-like characteristics in parents of ADHD cases.

The objective of this study was to characterize an attention deficit hyperactivity disorder (ADHD) endophenotype in non-affected parents of adolescents with a history of ADHD, based on the relationship between performance on a sustained attention test (continuous performance task, or CPT) and polymorphisms of the DRD4 gene. In a sample of 25 non-affected parents of adolescents with ADHD history obtained from a longitudinal study of a nonclinical population, and 25 non-affected parents of adolescents with no ADHD history, four groups were evaluated with respect to the presence or absence of the long allele polymorphism of the DRD4 gene (i.e., over seven repeats). Comparisons of CPT performance among the four study groups included the number of commission errors, the number of omission errors, mean reaction time on correct responses (MRT), and reaction time (RT) variability (mean standard deviation of RT in each block [SDRT, as variability], and the sigma and tau components of the ex-Gaussian approach). The group of non-affected parents of adolescents with ADHD history and at least one long allele of the DRD4 gene showed greater RT variability (measured by SDRT), which is best explained by the greater frequency of abnormally slow responses (measured by tau). An association between the presence of the long allele of the DRD4 gene polymorphism and ADHD-like failure in CPT performance was evident in the non-affected parents of adolescents with ADHD in childhood. These findings suggest that certain traits of CPT performance could be considered an ADHD endophenotype.

Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines.

BACKGROUND: Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients. METHODS: This research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment. RESULTS: The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group. CONCLUSIONS: The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

Age and DRD4 Genotype Moderate Associations Between Stimulant Treatment History and Cortex Structure in Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with dopaminergic imbalance and subtle volume decreases in the brain. Stimulants acutely enhance dopaminergic neurotransmission. Long-term effects of prolonged manipulation of the dopaminergic system on brain structure remain poorly understood; they could be beneficial or unfavorable and could be moderated by common genetic variants and/or age. METHOD: In a large observational ADHD cohort study (N = 316), the effects of cumulative stimulant treatment, genotype (for DAT1 haplotype and DRD4 variants), and treatment-by-genotype interactions on striatal, frontal, and hippocampal volumes and their interactions with age were evaluated. RESULTS: No main effects of treatment were found. Associations between treatment and bilateral frontal and left hippocampal volume depended on DRD4 genotype and age. At a younger age and lower treatment levels, but not at a younger age and higher treatment levels, carriers of the DRD4 7R allele showed decreased frontal cortex volumes. At an older age, carriers and non-carriers showed smaller frontal volumes irrespective of treatment history. Left hippocampal volume was similar to that in controls at average treatment levels and increased with treatment only in carriers of the DRD4 risk allele and at a younger age. No interaction effects were found in the striatum. CONCLUSION: Carriers of the DRD4 risk allele at a younger age might be sensitive to cortical remodeling after stimulant treatment. The cross-sectional nature of this study warrants cautious interpretation of age effects. The present findings, although of small effect size, might ultimately contribute to optimal care for individuals with ADHD.

mRNA expression of dopamine receptors in peripheral blood lymphocytes of computer game addicts.

Excessive playing of computer games like some other behaviors could lead to addiction. Addictive behaviors may induce their reinforcing effects through stimulation of the brain dopaminergic mesolimbic pathway. The status of dopamine receptors in the brain may be parallel to their homologous receptors in peripheral blood lymphocytes (PBLs). Here, we have investigated the mRNA expression of dopamine D3, D4 and D5 receptors in PBLs of computer game addicts (n = 20) in comparison to normal subjects (n = 20), using a real-time PCR method. The results showed that the expression level of D3 and D4 dopamine receptors in computer game addicts were not statistically different from the control group. However, the expression of the mRNA of D5 dopamine receptor was significantly down-regulated in PBLs of computer game addicts and reached 0.42 the amount of the control group. It is concluded that unlike with drug addiction, the expression levels of the D3 and D4 dopamine receptors in computer game addicts are not altered compared to the control group. However, reduced level of the D5 dopamine receptor in computer game addicts may serve as a peripheral marker in studies where the confounding effects of abused drugs are unwanted.

Haplotype and nucleotide variation in the exon 3-VNTR of the DRD4 gene from indigenous and urban populations of Mexico.

OBJECTIVE: To describe the population structure of the 48-bp variable number of tandem repeats (VNTR), located in exon 3 of the dopamine receptor D4 gene (DRD4), in 41 Tarahumara from northern Mexico, 20 Mixe from southern Mexico, and 169 people from Mexico City. METHODS: Genotypes for the DRD4-VNTR were determined, from which 15 Tarahumara, eight Mixe, and 37 urban homozygous individuals were sequenced. Repeat-allele frequencies were compared with other world populations. RESULTS: The DRD4-VNTR variation in Mexico City appeared similar to the world mean. For the Mixe and Maya, DRD4-VNTR diversity appeared closer to South American groups whereas the Tarahumara were similar to North American groups. People from Mexico City and the Mixe exhibited attributes of a large and admixed population and an isolated population, respectively. The Tarahumara showed endogamy associated with a substructure as suggested by a preliminary regional differentiation. For the DRD4-VNTR and/or the adjacent 5'-173 bp sequence, the three populations exhibited negative Tajima's D. Two new VNTR haplotypes were discovered: one in Mexico City and another among the Tarahumara. CONCLUSIONS: A differentiation in the DRD4-VNTR of global relevance occurs between northern and southern populations of Mexico suggesting that the Mexican Trans-volcanic Belt has been a major frontier for human dispersion in the Americas. Ancient trespass of this barrier appears thus related to a major change in the population structure of the DRD4-VNTR. Distinctive and independent patterns of DRD4-VNTR diversity occur among the two Mexican indigenous populations by a still undefined combination of drift and selection.

DRD2 C313T and DRD4 48-bp VNTR polymorphisms and physical activity of healthy men in Lower Silesia, Poland (HALS study).

BACKGROUND: Both animal and human studies have proved that the dopaminergic system of the brain controls many aspects of behavior, e.g. motivation, addiction, motor movement, locomotion. It has been hypothesized that dopamine signalling may regulate spontaneous physical activity as well. AIM: Literature data suggests that an intact function of dopamine receptors (DRD2-DRD4) inhibits physical activity. This study searched for associations between a propensity to be active (or sedentary) and genetic variants of DRD2 and DRD4. SUBJECTS AND METHODS: Invitations to participate in the study were sent to 900 randomly selected, adult men living in Lower Silesia, Poland. Genotyping of DRD2 C313T and DRD4 48-bp VNTR polymorphisms of enrolled subjects (371 (DRD2 C313T) and 397 (DRD4 48-bp VNTR)) was performed. Level of physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). RESULTS: No associations were found between level of physical activity (low, moderate, high) and the two polymorphisms: DRD2 C313T (p = 0.49) and DRD4 48-bp VNTR (p = 0.31). Studied subjects did not differ as to the number of hours spent sitting either. CONCLUSION: The results exclude the presence of significant relationships between polymorphic variants of the dopamine receptors genes and the level of physical activity in men.