Effects of the dopamine transporter gene on neuroimaging findings in different attention deficit hyperactivity disorder presentations.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a phenotipically and neurobiologically heterogeneous disorder. Deficiencies at different levels in response inhibition, differences in dopamine transporter genotype (DAT1) and various symptomatic presentations contribute to ADHD heterogeneity. Integrating these three aspects into a functional neuroimaging research could help unreval specific neurobiological components of more phenotipically homogeneous groups of patients with ADHD. During the Go-NoGo trial, we investigated the effect of the DAT1 gene using 3 T MRI in 72 ADHD cases and 24 (TD) controls that typically developed between the ages 8 and 15 years. In the total ADHD group, DAT1 predicted homozygosity for the 10R allele and hypoactivation in the anterior cingulate cortex and paracingulate cortex. There were no significant activation differences between DAT1 10R/10R homozygotes and 9R carriers in TD controls. Subjects with predominantly inattentive ADHD (ADHD-I) presentation with DAT1 10R/10R homozygous reduced neuronal activation during Go trial particularly in the frontal regions and insular cortex, and in the parietal regions during NoGo trial (brain regions reported as part of Default Mode Network- DMN). Additionally, DAT1 10R/10R homozygousness was associated with increased occipital zone activation during only the Go trial in the ADHD combined presentation (ADHD-C) group. Our results point the three main findings: 1) The DAT1 gene is 10R homozygous for differentiated brain activation in ADHD cases but not in the TD controls, supporting the DAT1 gene as a potential marker for ADHD, 2) The relationship between the DAT1 gene and the occipital regions in ADHD-C group which may reflect compensatory mechanisms, 3) The relationship between DAT1 gene and the reduced DMN suppression for 9R carriers probabaly stems from the ADHD-I group.

Increased cerebral blood flow in the right anterior cingulate cortex and fronto-orbital cortex during go/no-go task in children with ADHD.

OBJECTIVE: Arterial spin labeling (ASL) is a relatively new imaging modality in the field of the cognitive neuroscience. In the present study, we aimed to compare the dynamic regional cerebral blood flow alterations of children with ADHD and healthy controls during a neurocognitive task by using event-related ASL scanning. METHODS: The study comprised of 17 healthy controls and 20 children with ADHD. The study subjects were scanned on 3 Tesla MRI scanner to obtain ASL imaging data. Subjects performed go/no-go task during the ASL image acquisition. The image analyses were performed by FEAT (fMRI Expert Analysis Tool) Version 6. RESULTS: The mean age was 10.88 ± 1.45 and 11 ± 1.91 for the control and ADHD group, respectively (p = .112). The go/no-go task was utilized during the ASL scanning. The right anterior cingulate cortex (BA32) extending into the frontopolar and orbitofrontal cortices (BA10 and 11) displayed greater activation in ADHD children relative to the control counterparts (p < .001). With a lenient significance threshold, greater activation was revealed in the right-sided frontoparietal regions during the go session, and in the left precuneus during the no-go session. CONCLUSION: These results indicate that children with ADHD needed to over-activate frontopolar cortex, anterior cingulate as well as the dorsal and ventral attention networks to compensate for the attention demanded in a given cognitive task.

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T).

AIM: The aim of this study was to determine the prevalence of childhood psychopathologies in Turkey. METHOD: A nation-wide, randomly selected, representative population of 5830 children (6-13 years-old) enrolled as a 2nd,3rd or 4th grade student in 30 cities were evaluated for presence of a psychiatric or mental disorder by a Sociodemographic Form, Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL), and DSM-IV-Based Screening Scale for Disruptive Behavior Disorders in Children and Adolescents scales. Impairment criterion was assessed via a 3 point-Likert scale by the parent and the teacher independently. RESULTS: Overall prevalence of any psychopathology was 37.6% without impairment criterion, and 17.1% with impairment criterion. Attention-deficit hyperactivity disorder was the most frequent diagnosis, followed by anxiety (19.5% and 16.7% without impairment, 12.4% and 5.3% with impairment, respectively). Lower education level and presence of a physical or psychiatric problem of the parents were independent predictors of any psychopathology of the offspring. CONCLUSION: This is the largest and most comprehensive epidemiological study to determine the prevalence of psychopathologies in children and adolescents in Turkey. Our results partly higher than, and partly comparable to previous national and international studies. It also contributes to the literature by determining the independent predictors of psychopathologies in this age group.

Comparisons between sluggish cognitive tempo and ADHD-restrictive inattentive presentation phenotypes in a clinical ADHD sample.

There is a debate how different ADHD cases with a comorbid sluggish cognitive tempo (SCT) phenotype are from subjects with a pure inattentive ADHD presentation (ADHD-restrictive inattentive presentation). In this study, 214 patients aged 8-15 years from an ADHD outpatient clinic were assessed, and 100 typically developing controls (TD) were recruited as comparisons. No psychiatric comorbidities except for oppositional defiant disorder were allowed. We compared 29 cases with ADHD + SCT with 34 ADHD-RI cases and 92 TD subjects on sociodemographic profiles, CBCL subscales scores and neurocognitive findings. Regarding sociodemographic profiles (age, gender and parental education) and CBCL subscales, ADHD + SCT and ADHD-RI cases did not differ in any score (all p > 0.05). Comparing with SCT cases, ADHD-RI cases presented slower psychomotor speed and worse neurocognitive index (p < 0.001). We found that only SCT was independently associated with a lower performance in total memory score. ADHD-RI was independently associated with longer reaction time. Our findings suggest that although SCT might be expected to present longer reaction time, we found that slower psychomotor speed and longer reaction time scores were related to inattention. Overall, SCT and ADHD-RI groups were distinguished by differential associations with measures of memory and reaction time.

Prevalence of Childhood Affective disorders in Turkey: An epidemiological study.

AIM: To determine the prevalence of affective disorders in Turkey among a representative sample of Turkish population. METHODS: This study was conducted as a part of the "The Epidemiology of Childhood Psychopathology in Turkey" (EPICPAT-T) Study, which was designed by the Turkish Association of Child and Adolescent Mental Health. The inclusion criterion was being a student between the second and fourth grades in the schools assigned as study centers. The assessment tools used were the K-SADS-PL, and a sociodemographic form that was designed by the authors. Impairment was assessed via a 3 point-Likert type scale independently rated by a parent and a teacher. RESULTS: A total of 5842 participants were included in the analyses. The prevalence of affective disorders was 2.5 % without considering impairment and 1.6 % when impairment was taken into account. In our sample, the diagnosis of bipolar disorder was lacking, thus depressive disorders constituted all the cases. Among depressive disorders with impairment, major depressive disorder (MDD) (prevalence of 1.06%) was the most common, followed by dysthymia (prevalence of 0.2%), adjustment disorder with depressive features (prevalence of 0.17%), and depressive disorder-NOS (prevalence of 0.14%). There were no statistically significant gender differences for depression. Maternal psychopathology and paternal physical illness were predictors of affective disorders with pervasive impairment. CONCLUSION: MDD was the most common depressive disorder among Turkish children in this nationwide epidemiological study. This highlights the severe nature of depression and the importance of early interventions. Populations with maternal psychopathology and paternal physical illness may be the most appropriate targets for interventions to prevent and treat depression in children and adolescents.

White matter alterations related to attention-deficit hyperactivity disorder and COMT val(158)met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus).

INTRODUCTION: In this article, the COMT gene val(158)met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated. PATIENTS AND METHODS: A total of 71 children diagnosed with ADHD and 24 controls aged 8-15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA). RESULTS: First, an interaction between the COMT val(158)met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism. CONCLUSION: Significant differences reported here may be evidence that the COMT gene val(158)met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.

Altered structural connectivity is related to attention deficit/hyperactivity subtypes: A DTI study.

This study aimed to provide novel insights into the white matter (WM) microstructural properties of Attention Deficit/Hyperactivity Disorder (ADHD) subtypes by recruiting a relatively large sample of stimulant-naïve children and adolescents who had no comorbidity other than Oppositional Defiant Disorder and were homogenous according to the DAT1 gene polymorphism. A sample of 72 ADHD subjects and 24 controls aged 8-15 years were enrolled in the study. We applied tract-based spatial statistics to the DTI measures for obtaining fractional anisotropy (FA) and axial, radial diffusivity (AD, RD) measures to explore ADHD type-related differences in WM for the whole brain. Comparing ADHD-Combined group (ADHD-C) with the ADHD predominantly inattentive group (ADHD-I) we detected increased RD in several bilateral brain area and increased AD mostly in left side of the brain, including the body and splenium of the corpus callosum; the anterior and posteriors limbs of the internal capsule; the superior, anterior and posterior corona radiata; the posterior thalamic radiation; and the superior longitudinal fasciculus. Likewise, mostly in the overlapping brain areas, the ADHD-C group presented increased AD values than ADHD-RI. Significant differences among ADHD types could be a preliminary evidence that they have distinct microstructural properties. There were no significant differences in diffusivity between controls and both the ADHD group as whole or any ADHD subgroups.

Decreasing ADHD phenotypic heterogeneity: searching for neurobiological underpinnings of the restrictive inattentive phenotype.

During the process of developing the DSM-5, a new phenotype of ADHD was proposed-the ADHD restrictive inattentive presentation (ADHD-RI), describing subjects with high endorsement of inattentive symptoms and a low level of hyperactivity. However, this phenotype was not included in the DSM-5 because of the lack of robust neurobiological data. We aimed to assess the specific neurobiological underpinnings of individuals presenting ADHD-RI. We compared a sample of 301 subjects (101 ADHD-Combined; 50 ADHD-RI; 50 ADHD predominantly inattentive type and 100 typically developing subjects) aged 8-15 years, using a complete neuropsychological battery, molecular genetic data (DRD4 and DAT1 most studied polymorphisms) and functional MRI during a Go-No/Go task. Subjects with ADHD-RI had a significantly different neuropsychological profile compared with the other groups, including lower psychomotor speeds, longer reaction times and the worst overall performance in the global neurocognitive index. The proportion of subjects with the presence of DRD4-7 repeat allele was significantly higher in ADHD-RI. The fMRI data suggested that more attention-related posterior brain regions (especially temporo-occipital areas) are activated in ADHD-RI during both Go and No-Go cues compared to TD controls and ADHD predominantly inattentive type. ADHD-RI may represent a different phenotype than other types of ADHD. In addition, our results suggest that reducing the phenotypic heterogeneity may aid in the search for the neurobiological underpinnings of ADHD.