Serotonin 2A Receptor Gene Polymorphism in Korean Children with Attention-Deficit/Hyperactivity Disorder

Objective

The purpose of this study was to investigate the association between the T102C polymorphism in the serotonin 2A receptor gene and attention-deficit/hyperactivity disorder (ADHD) in Korean patients.

Methods

A total of 189 Korean children with ADHD as well as both parents of the ADHD children and 150 normal children participated in this study. DNA was extracted from blood samples from all of the subjects, and genotyping was conducted. Based on the allele and genotype information obtained, case-control analyses were performed to compare the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were used for family-based association testing (number of trios=113). Finally, according to the significant finding which was showed in the case-control analyses, the results of behavioral characterastics and neuropsychological test were compared between ADHD children with and without the C allele.

Results

In the case-control analyses, statistically significant differences were detected in the frequencies of genotypes containing the C allele (χ²=4.73, p=0.030). In the family-based association study, TDTs failed to detect linkage disequilibrium of the T102C polymorphism associated with ADHD children. In the ADHD children, both the mean reaction time and the standard deviation of the reaction time in the auditory continuous performance test were longer in the group with the C allele compared to the group without the C allele.

Conclusion

The results of this study suggest that there is a significant genetic association between the T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.     

Candidate genes involved in neural plasticity and the risk for attention-deficit hyperactivity disorder: a meta-analysis of 8 common variants

Background

Attention-deficit hyperactivity disorder (ADHD) is an important psychiatric condition in terms of its prevalence and impact on quality of life. It has one of the highest heritabilities found in psychiatric disorders. A number of association studies exploring several candidate genes in different populations around the world have been carried out. The objective of the present study was to carry out a meta-analysis for 8 common variants located in 5 top candidate genes for ADHD (BDNF, HTR1B, SLC6A2, SLC6A4 and SNAP25); these genes are known to be involved in synaptic transmission and plasticity.

Methods

We performed a search for published genetic association studies that analyzed the candidate polymorphisms in different populations, and we applied state-of-the-art meta-analytical procedures to obtain pooled odds ratios (ORs) and to evaluate potential basis of heterogeneity. We included 75 genetic association studies in these meta-analyses.

Results

A major part of the previously postulated associations were nonconsistent in the pooled odds ratios. We observed a weak significant association with a single nucleotide polymorphism (SNP) located in the 3′ UTR region of the SNAP25 gene (rs3746544, T allele, OR 1.15, 95% confidence interval 1.01–1.31, p = 0.028, I² = 0%). In addition to the low coverage of genetic variability given by these variants, phenotypic heterogeneity between samples (ADHD subtypes, comorbidities) and genetic background may explain these differences.

Limitations

Limitations of our study include the retrospective nature of our meta-analysis with the incorporation of study-level data from published articles.

Conclusion

To our knowledge, the present study is the largest meta-analysis carried out for ADHD genetics; previously proposed cumulative associations with common polymorphisms in SLC6A4 and HTR1B genes were not supported. We identified a weak consistent association with a common SNP in the SNAP25 gene, a molecule that is known to be central for synaptic transmission and plasticity mechanisms.     

Association of the Catechol O-Methyltransferase Val158-Met Polymorphism and Reduced Interference Control in Korean Children with Attention-Deficit Hyperactivity Disorder

Objective

We tested for association of the catechol-O-methyltransferase (COMT) Val¹⁵⁸-Met (rs4680) polymorphism with attention-deficit hyperactivity disorder (ADHD) using family-based test in Korean trios.

Methods

A total of 181 subjects with ADHD along with both of their biological parents were recruited from University Hospitals in Korea. We performed a transmission disequilibrium test (TDT) on 181 trios.

Results

In the TDT, we found the over-transmission of the Val allele in children with ADHD (χ²=4.21, p=0.040).

Conclusion

These results suggest that the COMT Val158-Met polymorphism is associated with ADHD among the Korean population. However, this study must be replicated in larger populations.     

Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit/hyperactivity disorder

Objective

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Brain-derived neurotrophic factor (BDNF), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, could play a role in ADHD development. We aimed to explore the relationships between ADHD and BDNF gene polymorphism.

Methods

We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test on 151 trios, and compared the results of a continuous performance test (CPT) according to the genotype of the three single nucleotide polymorphisms (rs11030101, rs6265, rs16917204) in the BDNF gene.

Results

In the case-control analysis, the AA genotype of the BDNF rs11030101 polymorphism was significantly associated with ADHD only in girls (p=0.024, odds ratio=3.00). The T-G-G haplotype was significantly less frequent (p=0.005) and A-G-G was more frequent (p=0.048) in girls with ADHD than in control girls (global p=0.027). A multivariate analysis of variance for commission errors on the CPT showed a significant main effect for the rs11030101 genotype (p=0.026) and an interaction effect of the rs11030101 genotype and gender (p=0.032) in ADHD probands.

Conclusion

These results provide preliminary evidence for a gender-specific association between BDNF and ADHD in the Korean population.     

Association of SNAP-25 Gene Ddel and Mnll Polymorphisms with Adult Attention Deficit Hyperactivity Disorder

Objective

The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters. Previously, several studies reported association between SNAP-25 and attention deficit hyperactivity disorder (ADHD). We investigated whether these SNAP-25 polymorphisms (MnlI T/G and DdelI T/C) were also associated with ADHD in the Turkish population.

Methods

Our study comprised unrelated 139 subjects who met DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale.

Results

SNAP-25 DdelI polymorphism was not associated with ADHD but there was a statistically significant difference between ADHD patients and controls for SNAP-25 MnlI polymorphism. For SNAP-25 MnlI polymorphism patients with G/G genotype of the SNAP-25 gene MnlI polymorphism had higher Wender-Utah scores and higher scores in the 1st and 3rd parts of adult ADD/ADHD Scale.

Conclusion

We detected a significant association of the MnlI polymorphism in our ADHD sample which was similar to previous findings. Our study also revealed that SNAP-25 MnlI polymorphism was also associated with symptom severity of ADHD. This study is also, the first report on the association of SNAP-25 with ADHD in the Turkish population.     

Association Study between Norepinephrine Transporter Gene Polymorphism and Schizophrenia in a Korean Population

Objective

We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia.

Methods

Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline.

Results

We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms.

Conclusion

Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results.     

Association between RELN Gene Polymorphisms and Attention Deficit Hyperactivity Disorder in Korean Children

Objective

Attention deficit hyperactivity disorder (ADHD) is common disorder of the school-age population. ADHD is familial and genetic studies estimate heritability at 80–90%. The aim of the present study was to investigate the association between the genetic type and alleles for RELNgene (rs736707, rs2229864, rs362746, rs362726, rs362691, rs1062831, rs607755, and rs2072403) in Korean children with ADHD.

Methods

The sample consisted of 180 ADHD children and 159 control children. We diagnosed ADHD according to DSM-IV. ADHD symptoms were evaluated with Conners'' Parent Rating Scales and Dupaul Parent ADHD Rating Scales. Blood samples were taken from the 339 subjects, DNA was extracted from blood lymphocytes, and PCR was performed for RELN Polymorphism. Alleles and genotype frequencies were compared using the chi-square test. We compared the allele and genotype frequencies of RELN gene polymorphism in the ADHD and control groups.

Results

This study showed that there was a significant correlation among the frequencies of the rs736707 (OR=1.40, 95% CI=1.03–1.90, p=0.031) of alleles of RELN, but the final conclusions are not definite.

Conclusion

Follow up studies with larger patient or pure subgroups are expected. These results suggested that RELN might be related to ADHD symptoms.     

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder.

Electronic supplementary material

The online version of this article (doi:10.1007/s11689-009-9033-8) contains supplementary material, which is available to authorized users.     

Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder

Background

Previous studies have suggested that there may be a parent-of-origin effect for attention-deficit/hyperactivity disorder (ADHD) candidate genes. The objective of the present study was to investigate parent-of-origin effects using a genome-wide association analysis of the International Multicentre ADHD Genetics (IMAGE) study sample.

Methods

Family-based association analysis for ADHD using 846 ADHD probands and their parents was performed using the PLINK program, and parent-of-origin effects were studied using a Z score for the difference in paternal versus maternal odds ratios.

Results

We identified 44 single nucleotide polymorphisms (SNPs) showing parent-of-origin effects at a significance level of p < 0.001. The most significant SNP, rs7614907, is at position 3q13.33 in the CDGAP gene (p = 0.000064 for parent-of-origin effect). Furthermore, 2 genes (FAS and PDLIM1) showed moderate parent-of-origin effects (p = 0.00086 for rs9658691 and p = 0.00077 for rs11188249) and strong maternal transmission (p = 0.000059 for rs9658691 and p = 0.0000068 for rs11188249). In addition, ZNF775 showed a moderate parent-of-origin effect (p = 0.00036 for rs7790549) and strong paternal transmission (p = 0.000041 for rs7790549).

Limitations

We only had 1 sample available for analysis.

Conclusion

These results suggest several genes or regions with moderate parent-of-origin effects, and these findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in ADHD.     

DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli

Background

The aim of the present study was to investigate the association of fMRI blood oxygen–level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD).

Methods

We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing.

Results

Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation.

Limitations

It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn.

Conclusion

Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery.     

Association of VAMP-2 and Syntaxin 1A Genes with Adult Attention Deficit Hyperactivity Disorder

Objective

The etiology of attention deficit hyperactivity disorder (ADHD) has not been entirely clarified yet. Structural and metabolic differences at the prefrontal striatal cerebellary system and the interaction of gene and environment are the main factors that thought to play roles in the etiology. Genetic investigations are performed especially about the dopamine pathways and receptors. In this study; it was aimed to investigate the association of the synaptobrevin-2 (VAMP-2) gene Ins/Del polymorphism and syntaxin 1A gene intron 7 polymorphism, which take place in encoding presynaptic protein, with adult ADHD.

Methods

One hundred thirty-nine patients, having ADHD aging between 18 and 60 years and 106 healthy people as controls were included into the study. DNA samples were extracted from whole blood and genetic analysis were performed.

Results

A significant difference was determined between ADHD and VAMP-2 Ins/Del polymorphism and syntaxin 1A intron 7 polymorphism according to the control group. These polymorphisms were found not to be associated with subtypes of ADHD.

Conclusion

It is supposed that synaptic protein genes together with dopaminergic genes might have roles in the etiology of ADHD.     

Evaluation of Oxidative Metabolism in Child and Adolescent Patients with Attention Deficit Hyperactivity Disorder

Objective

Oxidative metabolism is impaired in several medical conditions including psychiatric disorders, and this imbalance may be involved in the etiology of these diseases. The present study evaluated oxidative balance in pediatric and adolescent patients with attention deficit hyperactivity disorder (ADHD).

Methods

The study included 48 children and adolescents (34 male, 14 female) with ADHD who had no neurological, systemic, or comorbid psychiatric disorders, with the exception of oppositional defiant disorder (ODD), and 24 sex- and age-matched healthy controls (17 male and seven female).

Results

TAS was significantly lower, and TOS and OSI were significantly higher in patients with ADHD than in healthy controls. Total antioxidant levels were lower in patients with comorbid ODD than in those with no comorbidity. No difference was found in TOS or OSI among the ADHD subtypes; however, TAS was higher in the attention-deficient subtype.

Conclusion

Our findings demonstrated that oxidative balance is impaired and oxidative stress is increased in children and adolescents with ADHD. This results are consistent with those of previous studies.     

MRAS Genetic Variation Is Associated with Atherothrombotic Stroke in the Han Chinese Population

Background and Purpose

Atherothrombotic cerebral infarction [atherothrombotic stroke (ATS)] shares common risk factors and pathophysiological mechanisms with coronary artery disease (CAD), and both diseases appear to have common susceptibility loci. The muscle RAS oncogene homolog gene (MRAS) has been identified as a susceptibility locus for CAD and is implicated in atherosclerosis. The aim of this study was to elucidate whether the single-nucleotide polymorphisms (SNPs) and haplotypes of MRAS are associated with increased risk of ATS in a population of Han Chinese.

Methods

A case-controlled association study was conducted in which only patients with ATS (identified as a major subtype in the Korean modification of the Trial of Org 10172 in Acute Stroke Treatment classification) were enrolled. Subgroup analyses were carried out to determine whether the effect of the MRAS polymorphism was specific to age and gender among the subjects.

Results

In total, 194 ATS and 186 control subjects were included in the present study. Two tagging SNPs were identified in MRAS (rs40593 and rs3755751). A multivariate regression analysis revealed a positive association between rs40593 and ATS under dominant and additive models after adjustment for covariates. Subgroup analyses revealed that there were no gender differences with respect to allele or genotype frequencies between the groups. The AG genotype for rs40593 (p=0.028), the CT genotype for rs3755751 (p=0.036), and G-allele carriers (AG plus GG) for rs40593 (p=0.015) exhibited a significant protective effect among those aged ≥45 years. For the haplotype analysis, ATS subjects aged ≥45 years had a higher frequency of the ACAC haplotype (76.0%) than the controls (68.1%; p<0.05); that haplotype was associated with an increased risk of ATS.

Conclusions

The obtained data suggest a positive association between MRAS and ATS among the Han Chinese. Further studies should be performed with larger sample and among different ethnic populations, and gene-gene or gene-environment interactions should be considered.     

Association of Hair Manganese Level with Symptoms in Attention-Deficit/Hyperactivity Disorder

Objective

The study examined the association between hair manganese level and symptoms of attention-deficit/hyperactivity disorder (ADHD) in Korean children.

Methods

Forty clinic-referred children with ADHD and 43 normal control children participated in this study. The participants were 6-15 years old and were mainly from the urban area of Seoul, Korea. ADHD was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition and Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version. The severity and symptoms of ADHD was evaluated according to the ADHD Diagnostic System, and parent''s Korean ADHD Rating Scale (K-ARS). All participants completed intelligence test and hair mineral analysis. We divided the data of hair Mn into two groups to determine whether a deficit or excess of Mn are associated with ADHD. Multiple logistic regression analyses were performed to identify hair manganese levels associated with ADHD, controlling for age, sex, and full scale intelligence quotient (IQ).

Results

The proportion of abnormal range Mn group was significantly high in ADHD compared to controls. However, after statistical control for covariates including age and sex, abnormal range Mn group was significantly associated with ADHD (OR=6.40, 95% CI=1.39-29.41, p=0.017).

Conclusion

The result of this study suggests that excess exposure or deficiency of Mn were associated with ADHD among children in Korea. Further investigation is needed to evaluate the effects of hair manganese levels on symptoms in ADHD.     

Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder

Background

Norepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input.

Methods

The expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9–10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6–7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7–14 pairs).

Results

Astrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods.

Limitations

Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide.

Conclusion

Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.     

Comorbid Depressive Disorders in ADHD: The Role of ADHD Severity,Subtypes and Familial Psychiatric Disorders

Objective

To evaluate the presence of Major Depressive Disorder (MDD) and Dysthymic Disorder (DD) in a sample of Italian children with Attention Deficit Hyperactivity Disorder (ADHD) and to explore specific features of comorbid depressive disorders in ADHD.

Methods

Three hundred and sixty-six consecutive, drug-naïve Caucasian Italian outpatients with ADHD were recruited and comorbid disorders were evaluated using DSM-IV-TR criteria. To evaluate ADHD severity, parents of all children filled out the ADHD Rating Scale. Thirty-seven children with comorbid MDD or DD were compared with 118 children with comorbid conduct disorder and 122 without comorbidity for age, sex, IQ level, family psychiatric history, and ADHD subtypes and severity.

Results

42 of the ADHD children displayed comorbid depressive disorders: 16 exhibited MDD, 21 DD, and 5 both MDD and DD. The frequency of hyperactive-impulsive subtypes was significantly lower in ADHD children with depressive disorders, than in those without any comorbidity. ADHD children with depressive disorders showed a higher number of familial psychiatric disorders and higher score in the Inattentive scale of the ADHD Rating Scale, than children without any comorbidity. No differences were found for age, sex and IQ level between the three groups.

Conclusion

Consistent with previous studies in other countries, depressive disorders affect a significant proportion of ADHD children in Italy. Patient assessment and subsequent treatment should take into consideration the possible presence of this comorbidity, which could specifically increase the severity of ADHD attention problems.     

Genetic Association Study of the Alpha 7 Nicotinic Receptor (CHRNA7) with the Development of Schizophrenia and Bipolar Disorder in Korean Population

Objective

CHRNA7 has been shown to be a strong candidate gene for schizophrenia and bipolar disorder. It is located on chromosome 15q13-q14, which is one of the replicated linkage spots for schizophrenia and bipolar disorder.

Methods

We conducted an association study to determine whether previous positive association is replicable in the Korean population. We included 254 patients with schizophrenia, 193 patients with bipolar disorder type I, 38 patients with bipolar disorder type II, 64 schizoaffective disorder patients, and 349 controls. All subjects were ethnically Korean. A total of 898 subjects were included, and genotyping was done for three single nucleotide polymorphisms (SNPs) of CHRNA7. These three intronic SNPs were rs2337506 (A/G), rs6494223 (C/T), and rs12916879 (A/G).

Results

There was only one marginally significant association; this association was between rs12916879 and bipolar disorder type I in the male subgroup. In both the allele and genotype distributions, we found a weak signal (Chi-squared=3.57, df=1, p=0.06 for allele, Chi-squared=7.50, df=2, p=0.02 for genotype) only. Unphased haplotype analysis could not provide additional support for this finding. No SNP was associated with schizophrenia or any other affected groups in this Korean sample. The associative finding is marginal and inconclusive.

Conclusion

We could not replicate positive association in other ethnic groups previously studied. This suggests possible heterogeneity in the genes associated with schizophrenia and bipolar disorders. Because of structural complexity of the CHRNA7 gene and the limited statistical power of this study, further genetic studies with more SNPs and larger samples covering various populations, along with more fine molecular exploration of the CHRNA7 gene structure, are required.     

Clinical correlations of grey matter reductions in the caudate nucleus of adults with attention deficit hyperactivity disorder

Background

Magnetic resonance imaging (MRI) studies have shown decreased caudate volumes in individuals with attention deficit hyperactivity disorder (ADHD). However, most of these studies have been carried out in male children. Very little research has been done in adults, and the results obtained in children are difficult to extrapolate to adults. We sought to compare the volume of the caudate of adults with ADHD with that of healthy controls; we also compared these volumes between men and women.

Methods

We performed an MRI scan on 20 adults with ADHD (10 men and 10 women) aged 25–35 years and 20 healthy controls matched by age and sex. We used voxel-based morphometry with the DARTEL algorithm for image analyses. We used the specifically designed Friederichsen, Almeida, Serrano, Cortes Test (FASCT) to measure the severity of ADHD; both the self-reported (FASCT-SR) and the observer (FASCT-O) versions were used.

Results

The statistical parametric map showed a smaller region with low grey matter volume and a smaller concentration of grey matter in this region of the right caudate in ADHD patients than in health controls, both in the entire sample and within each sex. There was a significant correlation between the volume of this region of the caudate with the number of DSM IV-TR criteria, as well as with the total scores and most of the factors of the FASCT-SR and FASCT-O scales. A separate correlation analysis by sex gave similar results.

Limitations

The study design was cross-sectional.

Conclusion

The region of the right caudate with low grey matter volume was smaller in adults with ADHD in both sexes and was correlated with ADHD severity.