Increased Serum Brain-derived Neurotrophic Factor, Nerve Growth Factor, Glial-derived Neurotrophic Factor and Galanin Levels in Children with Attention Deficit Hyperactivity Disorder, and the Effect of 10 Weeks Methylphenidate Treatment.

Objective: This study aimed to investigate the levels of serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF) and galanin in children with attention deficit hyperactivity disorder (ADHD). Methods: The study included 58 cases with ADHD and 60 healthy controls. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) together with Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) criteria were used for diagnostic evaluation. Sociodemographic data form and Conners' Parent/Teacher Rating Scale-Revised:Long Form were applied to all cases. The serum levels of BDNF, NGF, GDNF, and galanin were evaluated in all subjects. Afterwards, methylphenidate was started in the ADHD group. ADHD cases were reevaluated in terms of the serum levels of BDNF, NGF, GDNF, galanin at the 10th week of treatment. Results: Before the treatment, the levels of BDNF, NGF, GDNF, galanin were significantly higher in the ADHD group compared to the control group. The levels of BDNF, NGF, GDNF, galanin were found to be significantly lower after treatment in ADHD group compared to pre-treatment. No correlation was between scale scores and the serum levels of BDNF, NGF, GDNF, galanin. Conclusion: The levels of neurotrophic factors and galanin were thought to be parameters worth evaluating in ADHD. Further studies on the subject with longer-term treatments and larger sample groups are required.

Altered Arginine/Nitric Oxide Pathway in Children Diagnosed Attention Deficit Hyperactivity Disorder, and the Effect of 10 Weeks Methylphenidate Treatment.

Objective: In this study, we investigated the levels of arginine, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and adrenomedullin that are presumed to play a role in attention deficit hyperactivity disorder (ADHD) etiology, and to compare the findings with healthy controls. Methods: Thirty ADHD patients and thirty healthy control subjects aged 6-12 years were included in the study. Sociodemographic data form, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version; Conners' Parent/Teacher Rating Scale-Revised: Long Form; Children's Depression Inventory; and The State-Trait Anxiety Inventory for Children were applied to all cases. All participants included in the study were evaluated in terms of their serum arginine, NO, ADMA, and adrenomedullin levels. Subsequently, methylphenidate treatment was started in ADHD patients and blood parameters were tested again in the tenth week of treatment. Results: At the start of the study, arginine and ADMA levels were significantly higher and NO and adrenomedullin levels were significantly lower in the ADHD group compared to the control group. Post-treatment arginine and ADMA levels were found to be significantly lower than in the pre-treatment period. There were no significant differences in NO and adrenomedullin levels before and after treatment. There was no correlation between scale scores and blood parameters. Conclusion: These variations in the blood parameters of the ADHD group seem to be worth further investigation. Studies to be conducted with larger sample groups after longer-term treatment may provide new information about the alterations in neurobiological processes related to ADHD etiology and treatment.

Effect of Impairment on the Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder in a National Survey: Nation-Wide Prevalence and Comorbidities of ADHD.

OBJECTIVE: This study aimed to determine the prevalence and comorbidities of attention-deficit hyperactivity disorder (ADHD) by evaluating a large-scale nation-wide sample of children. METHOD: The inclusion criterion was being enrolled as a 2nd, 3rd, or 4th-grade student. A semi-structured diagnostic interview (K-SADS-PL), DSM-IV-Based Screening Scale for Disruptive Behavior Disorders, and assessment of impairment (by both parents and teachers) were applied to 5,842 participants. RESULTS: The prevalence of ADHD was 19.5% without impairment and 12.4% with impairment. Both ADHD with and without impairment groups had similar psychiatric comorbidity rates except for oppositional defiant disorder (ODD) and conduct disorder (CD) diagnoses. Impairment in the ADHD group resulted in significantly higher ODD and CD diagnoses. CONCLUSION: Even when impairment is not described, other psychiatric disorders accompany the diagnosis of ADHD and may cause impairment in the future. Impairment in the diagnosis of ADHD significantly increases the likelihood of ODD and CD.

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.

Decreased theory of mind skills, increased emotion dysregulation and insight levels in adolescents diagnosed with obsessive compulsive disorder.

Background: An abnormal interaction between cognition and emotion may contribute to the development of obsessive-compulsive disorder (OCD). Aims: In this study, we aimed to evaluate theory of mind and emotion regulation skills in adolescents diagnosed with OCD. In addition, the results were evaluated in accordance with patients' insight levels. Methods: This study was conducted with 50 patients, who were aged between 11 and 16 and who were newly diagnosed with OCD and 50 healthy individuals. The Turkish version of the Schedule for Affective Disorders and Schizophrenia for School Age Children - Present and Lifetime was used to diagnose OCD and other comorbidities. The Children's Yale-Brown Obsessive Compulsive Scale, the Children's Depression Inventory, and the State-Trait Anxiety Inventory for Children were used for clinical evaluation. The intelligence levels were assessed using the Wechsler Intelligence Scale for Children-Revised Short Form. Reading the Mind in the Eyes Test was used in patients. The Difficulties in Emotion Regulation Scale was also used to evaluate the skills of regulating emotions. Results: Patients with OCD had lower ability with regard to reading minds in the eyes and emotion regulation than the healthy individuals. Patients with OCD, who had a poor insight, had more difficulty in reading minds in the eyes and emotion regulation than those with good insight. Conclusions: This study supports the idea that OCD is related to deficits in theory of mind and emotion regulation skills. Thus, further studies are required to confirm the findings of this study.

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.

Increased Serum Hepcidin Levels in Children and Adolescents with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: In this study, we aimed to evaluate the serum hepcidin levels in attention deficit hyperactivity disorder (ADHD) patients that were newly diagnosed with no history of psychotropic drugs. METHODS: A total of 70 ADHD patients and 69 healthy controls were enrolled in our study. During the diagnosis, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version were applied. The sociodemographic data form, Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale, and Conners' Rating Scales-Revised: Long Form were used for the clinical evaluation. Serum hepcidin levels were measured and compared between the groups. RESULTS: No significant difference between the groups in terms of age (p=0.533) and gender (p=0.397) was determined. In addition, the groups did not differ significantly for the other sociodemographic variables recorded. Serum hepcidin levels were found to be significantly higher in the patients with ADHD than healthy controls (p=0.019). CONCLUSION: To the best of our knowledge, this study is the first to evaluate the total serum hepcidin levels in ADHD patients. Our study findings may suggest that high levels of hepcidin may cause iron dysregulation in ADHD patients. However, further studies are required to establish a definite conclusion.

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.

Vitamin D levels in children and adolescents with obsessive compulsive disorder.

BACKGROUND: Recent studies showed that vitamin D deficiency may lead to dysfunctional changes in the brain and may be associated with neuropsychiatric diseases. AIMS: The present study aims to investigate vitamin D, calcium, phosphorus and alkaline phosphatase levels in children and adolescents diagnosed with obsessive-compulsive disorder (OCD) and compared them to healthy controls. Additionally, the correlation of OCD symptom severity with serum vitamin D level will be analyzed. METHODS: A semi-structured interview form (K-SADS-PL) was used to diagnose OCD and other comorbidities in accordance with DSM-IV criteria. In addition, all participants were assessed with clinical interviews based on DSM-5 OCD diagnostic criteria. Children's Yale Brown Obsession Compulsion Scale (CY-BOCS) and Children's Depression Inventory were used in the clinical evaluation. RESULTS: Vitamin D levels were lower in patients diagnosed with OCD (15.88 ± 6.96 ng/mL) when compared to healthy controls (18.21 ± 13.24 ng/mL), but the difference was not statistically significant (p = .234). Serum calcium, serum phosphate and serum alkaline phosphatase levels were not different between the groups. A negative correlation was found between serum 25OH-D3 levels and obsession scale scores in CY-BOCS. CONCLUSIONS: To our knowledge this is the first study that evaluated vitamin D levels in OCD patients without comorbidity. The vitamin D levels of newly diagnosed OCD cases were lower but not statistically different than healthy controls. Furthermore, the study does also not support the presence of a significant association between serum vitamin D levels and OCD.

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.

Iron Deficiency Parameters in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

The aim of this study is to compare iron deficiency parameters in patients with stimulant-naive attention-deficit/hyperactivity disorder (ADHD) and healthy controls, to investigate whether there are differences among the ADHD presentations, and to evaluate the relationship between ADHD symptom severity and serum ferritin levels. In addition, ADHD-Predominantly Inattentive (ADHD-PI) patients with restrictive hyperactivity/impulsivity symptoms were evaluated as a separate group with "restrictive inattention presentation" (ADHD-Rest) and were compared with other groups. Patients with ADHD-Rest are typically defined as having six or more symptoms of inattention and fewer than three symptoms of hyperactivity/impulsivity. A total of 200 ADHD cases consisting of 100 ADHD-Combine (ADHD-C) and 100 ADHD-PI and a total of 100 healthy control cases were included in the study. The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version was performed in a semi-structured interview during the diagnosis. The Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale, the Conners' Rating Scale-Revised: Long Form (Parent-Teacher) (CPRSR:L, CTRS-R:L) were used for clinical evaluation. Hemogram, serum iron, iron binding capacity and serum ferritin levels were assessed. There were no significant differences between the ADHD patients and the healthy control cases in terms of iron deficiency parameters. Further, there were no significant differences among the ADHD presentations in terms of the same parameters, nor were there any significant differences when the groups were examined after the identification of the ADHD-Rest. The CPRS-R:L Hyperactivity and the CTRS-R:L Hyperactivity scores were negatively correlated with serum ferritin level in the ADHD group. To our knowledge, our current study is the first to compare serum ferritin levels in ADHD-Rest with other presentations of ADHD, and included the largest number of patients that were classified by ADHD presentations. Elucidation of these findings is important for both the etiology and treatment of ADHD.

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.

Prevalence and diagnostic stability of ADHD and ODD in Turkish children: a 4-year longitudinal study.

BACKGROUND: This study was designed to assess the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD) in a representative sample of second grade students from a country in a region where no previous rates are available (Turkey). The second aim is to evaluate the differences in ADHD and ODD prevalence rates among four different waves with one-year gap in reassessments. METHOD: Sixteen schools were randomly selected and stratified according to socioeconomic classes. The DSM-IV Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S) was delivered to parents and teachers for screening in around 1500 children. Screen positive cases and matched controls were extensively assessed using the K-SADS-PL and a scale to assess impairment criterion. The sample was reassessed in the second, third and fourth waves with the same methodology. RESULTS: The prevalence rates of ADHD in the four waves were respectively 13.38%, 12.53%, 12.22% and 12.91%. The ODD prevalence was found to be 3.77% in the first wave, 0.96% in the second, 5.41% in the third and 5.35% in the fourth wave. Mean ODD prevalence was found to be 3.87%. CONCLUSIONS: The prevalence rates of ADHD in the four waves were remarkably higher than the worldwide pooled childhood prevalence. ADHD diagnosis was quite stable in reassessments after one, two and three years. A mean ODD prevalence consistent with the worldwide-pooled prevalence was found; but diagnostic stability was much lower compared to ADHD.