Omer Basay

Abnormal white matter integrity and impairment of cognitive abilities in adolescent inhalant abusers.

Inhalant abuse represents a major health problem especially among adolescents and young adults. However, less is known about white matter (WM) microstructure in adolescent inhalant abusers. In the present study, we used diffusion tensor imaging (DTI) to study WM changes in adolescent inhalant abusers compared with healthy controls. We also tested whether there was any relationship between WM integrity and neuropsychological measures in adolescent inhalant abusers. The study included 19 adolescent inhalant abusers and 19 healthy control subjects. Whole brain analysis of WM microstructure was performed using tract-based spatial statistics (TBSS) to detect abnormal WM regions between groups. Wisconsin card sorting test (WCST) and Stroop test were used to measure neuropsychological performance. We found that adolescent inhalant abuser group had significantly higher axial diffusivity (AD) values in left parietal, occipital and temporal WM than in healthy control group. Inhalant abuser and control groups did not differ significantly on fractional anisotropy (FA) and radial diffusivity (RD) values. Adolescent inhalant abusers showed worse performance when compared with control group in WCST and Stroop test. There was no significant correlation of AD values in significant clusters with neuropsychological test performances within the two groups. We only found discrete impairments in neuropsychological test performance and WM integrity in adolescent inhalant abusers compared with healthy control subjects and we were not able to demonstrate a direct correlation between WM alterations and neurocognitive performance. Future work is required to longitudinally evaluate brain abnormalities through methods assessing brain structure, function and connectivity.

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 val158met 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 val158met 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 val158met 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.

Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole.

The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity.

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Is a Risk Factor for Attention-Deficit Hyperactivity Disorder in a Turkish Sample

Objective Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD. Methods Two hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teachers Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms. Results The GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes. Conclusion We found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.

Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder

Modafinil is generally known as a drug with low addiction potential. There are few case reports in the literature demonstrating that Modafinil, stated being capable of diminishing symptoms of attention deficit/hyperactivity disorder (ADHD), causes addiction. In the present article a Modafinil addicted ADHD case, consuming usurious doses (5,000 mg/per day) of Modafinil is presented. The case presented to our psychiatry outpatient clinic due to: requirement of in taking high dose Modafinil in order to achieve the initial effects, difficulty in obtaining the drug, irritability, anxiousness, sleep irregularities, fatigue and unpleasant vivid dreams when he did not use the drug. It was realized that the patient, himself increased doses of Modafinil incrementally, in order to keep its effects on attention symptoms at the same level. It has to be kept in mind that ADHD patients can develop Modafinil addiction. It is necessary to carry out systemic studies on this subject.

The impact of synapsin III gene on the neurometabolite level alterations after single-dose methylphenidate in attention-deficit hyperactivity disorder patients.

Objective To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). Methods Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel 1H MRS when medication naïve and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. Results After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016). Conclusion Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings.

The Effect of Single Dose Methylphenidate on Neurometabolites according to COMT Gene Val158Met Polymorphism in the Patient with Attention Deficit Hyperactivity Disorder: A Study Using Magnetic Resonance Spectroscopy.

Objective Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene. Methods This study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum. Results The NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers. Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers. Conclusion These findings suggest that polymorphisms of the COMT gene can account for individual differences in neuro-chemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.

Does the quality of life in autism spectrum disorder differ from other chronic disorders and healthy children

Objective: Autism spectrum disorder (ASD) is characterized by deficits in social interaction, communication, restricted interests, and repetitive patterns of behavior. This study examined quality of life (QoL) and related clinical factors in children with ASD, compared to children with Attention Deficit Hyperactivity Disorder (ADHD), children with asthma, and healthy controls (HC). Methods: QoL was assessed by the Pediatric Quality of Life Inventory 4.0 (PedsQLTM 4.0). Additionally, parents of the children provided socio-demographic information and filled out an evaluation questionnaire, child behavior check list (CBCL), and Turgay DSM-IV disruptive behavior disorders rating scale (T-DSM-IV-S). Results: The physical health, psychosocial health, social functioning, and scale total score of the ASD group were significantly lower than those of the three comparison groups. The school functioning score domain was lower in the ASD group than in the asthma and HC groups. In contrast, the emotional functioning domain assessments did not reveal statistically significant differences between the ASD group and the comparison groups. In the ASD group, the total problem score, inattention, and hyperactivity scores were significantly higher than both the asthma and HC groups, and the internalizing scores were higher than the healthy group. Conclusion: The poor QoL is most likely due to functional losses and problem behaviors related to ASD and may negatively affect not only children with ASD but also the whole life of the family.