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  • Küçük Resim
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    Plasma norepinephrine and dopamine levels in prepubertal male children with attention-deficit hyperactivity disorder do not change with 8 weeks of methylphenidate treatment
    (Kure Iletisim Grubu A S, 2015) Alsen, Sevay; Resmi, Halil; Özek, Handan; Tufan, Ali Evren; Bülbül, Memduh
    Objectives:The aim of this study was to determine plasma norepinephrine and dopamine levels at baseline and after 8 weeks of stimulant treatment in pre-pubertal male children with ADHD. Methods: The study group consisted of 50 children (6-12 years old) diagnosed with ADHD. The control group comprised students from a primary school within the epidemiological catchment area of the clinic and was matched for class and age to the ADHD patients. The Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) was used to diagnose ADHD and allowed comorbidities. Mental retardation was ruled out with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and impaired functioning. We evaluated disorder severity at the time of assessment using the Clinic Global Impression Scale (CGI). The DuPaul ADHD Rating Scale-IV (ARS) was also used. All patients were treatment-naive. The parents were advised to use OROS methylphenidate daily with no drug holidays during weekends. No rescue medications (immediate-release methylphenidate) were allowed. The dose started at 18 mg and was titrated to 54 mg in 4 weeks to yield average doses of 1 mg/kg/day. Baseline and endpoint plasma DA and NE were measured. Results: Baseline plasma NE and DA levels had no statistically significant differences between ADHD patients and controls (232.0 +/- 67.3 versus 232.2 +/- 65.3 pg/mL and 169.3 +/- 48.4 versus 186.9 +/- 40.5 pg/mL). Plasma NE levels in all ADHD subgroups decreased with 8 weeks of stimulant treatment, while changes in DA levels were more complex. Plasma DA levels decreased with treatment in the ADHD-inattentive subgroup but were elevated in the hyperactive/impulsive and combined subgroups. There were no statistically significant differences between ADHD subgroups for these variables. Endpoint NE levels were correlated with endpoint DA levels. There were no statistically significant differences between ADHD subgroups. Plasma NE levels were not related to symptom severity or treatment response. In contrast, baseline DA levels were negatively correlated with ARS total scores. Conclusions: We found no statistically significant differences between plasma levels of NE and DA in a prepubertal male sample with ADHD and controls. Plasma DA and NE levels were correlated at both baseline and the endpoint. Although there was a signal that baseline DA levels may correlate with ADHD symptoms as evaluated via ARS, this was not true for endpoint analyses. Because this negative correlation disappeared after treatment, this finding about baseline DA levels may also be evaluated as an early treatment neuromarker. The negative results could also be explained by our focus on plasma. The recent consensus is that urinary levels of NE and DA may be more informative in patients with ADHD and that concurrent evaluation of multiple neurotransmitter systems (i.e., neuropeptide Y and NE) may be more informative. Further studies may benefit from concurrent measurements of plasma and urinary levels of catecholamines and their metabolites.
  • Küçük Resim
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    Serum brain-derived neurotrophic factor levels in treatment?naïve boys with attention-deficit/hyperactivity disorder treated with methylphenidate: an 8-week, observational pretest-posttest study
    (Springer, 2018) Akay, Aynur Pekcanlar; Resmi, Halil; Güney, Sevay Alsen; Erkuran, Handan Özek; Özyurt, Gonca; Sargın, Enis; Topuzoğlu, Ahmet; Tufan, Ali Evren
    Brain-derived neurotrophic factor (BDNF) is an important neurotrophin in the brain that modulates dopaminergic neurons. In this study, we aimed to investigate the changes in serum BDNF levels of children with attention-deficit/hyperactivity disorder (ADHD) in response to OROS methylphenidate treatment. We also aimed to determine whether there were any pre-post-differences between ADHD subtypes and comorbid psychiatric disorders in serum BDNF levels. Fifty male children with ADHD and 50 male healthy controls within the age range of 6-12 years were recruited to the study. The psychiatric diagnoses were determined by applying a structured interview with Kiddie schedule for affective disorders and schizophrenia for school-age children-present and lifetime version. The symptom severity of ADHD was measured using the Clinical Global Impression ADHD Severity Scale (CGI-S). Physicians completed Du Paul ADHD questionnaires. The levels of serum BDNF were assessed before and after 8 weeks of treatment with effective dosages of OROS methylphenidate. In the present study, the mean serum BDNF levels of boys with ADHD and of the healthy controls were 2626.33 +/- 1528.05 and 2989.11 +/- 1420.08 pg/mL, respectively. Although there were no statistically significant difference between the ADHD group and healthy controls at baseline (p = 0.22), the increase of serum BDNF was statistically significant from baseline to endpoint in the ADHD group (p = 0.04). The mean serum BDNF levels at baseline and endpoint of the ADHD group were 2626.33 +/- 1528.05 and 3255.80 +/- 1908.79 pg/mL, respectively. The serum BDNF levels of ADHD-inattentive subtype were significantly lower at baseline (p = 0.02), whereas BDNF levels post-treatment showed no significant difference. The increase of serum BDNF levels with methylphenidate treatment after 8 weeks was significantly higher in the inattentive group (p = 0.005). The increase of serum BDNF levels with methylphenidate treatment after 8 weeks in boys with ADHD may support the potential role of BDNF in the pathophysiology of ADHD. The role of BDNF in ADHD subtypes in particular should be evaluated with further, larger studies.