neuropeptide-y and Attention-Deficit-Disorder-with-Hyperactivity

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and characterized by inattention, hyperactivity, and impulsivity. ADHD is a neurodevelopmental disorder, and its etiology has not yet been determined precisely. Orexin A is thought to play an important role in different forms of learning, memory, and attention. Despite its importance in attention and learning, no study has investigated serum orexin levels in patients with ADHD. In the present study, we aimed to compare serum orexigenic neuropeptides such as orexin A and orexin B, neuropeptide Y, and ghrelin between drug naive children with ADHD and healthy children. Fifty-six drug-naive children with ADHD and 40 healthy controls were enrolled in the study. After comparison of serum orexin A and orexin B, neuropeptide Y, and ghrelin, we found that serum orexin A levels were significantly lower in the ADHD group (p = 0.001). Furthermore, serum orexin A levels were compared between ADHD subgroups. Orexin A levels were significantly lower in the inattentive subtype compared with the hyperactive subtype and combined subtype (p = 0.009). Our results indicate that orexin A might be a neurobiological etiological factor in ADHD, particularly associated with attention symptoms. The present study is the first to demonstrate decreased serum orexin A levels in drug-naive children with ADHD. Further studies are needed to confirm our results and to show the effects of treatments involving orexin A in patients with ADHD.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Checklist; Child; Female; Ghrelin; Humans; Male; Neuropeptide Y; Orexins; Psychiatric Status Rating Scales; Statistics, Nonparametric

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in adolescence, however, the etiology has not been described. Neuropeptide Y (NPY) is one potential factor that may be involved in the etiology of ADHD. The goal of this study was to evaluate NPY levels in children with ADHD and compare the findings to healthy controls.. Forty-eight ADHD patients and 40 healthy controls were included in this study. The age range of ADHD patients was 6 to 16 years. All patients were diagnosed according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V).. The NPY levels of children with ADHD were compared to healthy controls but were not significantly different (t (86)= -0.887,  p= 0.378). NPY levels were similar (F= 0.191, p= 0.826) between ADHD presentations, and included 8 children with predominantly hyperactive-impulsive type (14.3%), 14 children with predominantly inattentive type (30.4%), and 26 children with a combined type (55.4%). There was also no difference between ADHD patients using medical treatment, ADHD patients not using medical treatment, and control subjects in terms of NPY levels (F= 0.572, p= 0.566). There was a significant positive correlation between age and NPY levels in the ADHD group (r= 0.349, p= 0.015).. This study demonstrated that the NPY levels of ADHD subjects were not different than those of controls. Future studies with homogeneous phenotypes and a larger sample population are needed.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Case-Control Studies; Child; Child Health; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Neuropeptide Y

ADHD is one of the most common childhood psychiatric disorders. Research indicates that there is some link between obesity/overweight and ADHD, though the mechanism of this association remains uncertain. It is the aim of the present study to explore the association between ADHD, obesity, and plasma leptin, neuropeptide Y (NPY), and adiponectin levels.. Thirty-six patients diagnosed with ADHD were included in the study. The control group consisted of 40 healthy children and adolescents who had similar age and gender features with the patient group. Plasma leptin, adiponectin, NPY levels were measured, and body mass index (BMI), weight for height, and standard deviation scores (SDS) of height, weight, and BMI were calculated.. No significant difference was found between patients and healthy children in terms of BMI and BMI percentile. Participants were classified into three groups according to their weight to height values. There was no significant difference between the two groups, but 10% of the control group and 30.6% of the ADHD group were classified as overweight, which was 3 times higher than the control group. The adiponectin plasma level was significantly lower and leptin/adiponectin (L/A) ratio was significantly higher in the ADHD group. There was no significant difference between serum NPY levels. In the ADHD group, the mean leptin plasma level was high, but was not statistically significant.. We think that a low adiponectin level and high L/A ratio may be the underlying mechanism of the obesity in ADHD patients.

Topics: Adiponectin; Adolescent; Attention Deficit Disorder with Hyperactivity; Case-Control Studies; Child; Female; Humans; Leptin; Male; Neuropeptide Y; Pediatric Obesity

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 α subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a ∼3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P=0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Brain; Child; Chromosome Mapping; Chromosomes, Human, Pair 7; Cohort Studies; Comparative Genomic Hybridization; DNA Copy Number Variations; Family Health; Female; Gene Dosage; Genome-Wide Association Study; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Neuropeptide Y; Oxygen; Pedigree; Phenotype

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, i.p.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7-35. Thirty-nine days after the last MPH administration (PND 76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7-11 per group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6+/-1.2 to 126+/-1.8 mmHg; p<0.05), assessed on PND 130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND 135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6 per group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood.

Topics: Analysis of Variance; Animals; Animals, Newborn; Attention Deficit Disorder with Hyperactivity; Behavior, Animal; Blood Pressure; Brain; Catecholamines; Cell Count; Central Nervous System Stimulants; Dentate Gyrus; Disease Models, Animal; Female; Hippocampus; Immunohistochemistry; Injections, Intraperitoneal; Male; Methylphenidate; Neurons; Neuropeptide Y; Pregnancy; Rats; Rats, Sprague-Dawley; Stress, Physiological; Weight Loss

Against a background of (a) increased drinking behavior in children with attention-deficit hyperactivity disorder (ADHD); (b) the parallel between some behaviors associated with ADHD and hypertension; (c) the use of the spontaneously hypertensive rat as a model for ADHD; and (d) similarities in the changes of neuropeptide Y (NPY) and catecholamine in studies of hypertension and drinking, NPY, catecholamines and electrolyte balance were compared in the plasma and urine of healthy children and those with ADHD. Drinking was monitored during 3 h of neuropsychological tests over 2 days in 14 ADHD and nine healthy children. Patients drank four times as much water and showed twice the levels of NPY found in controls. In controls there were positive and in patients there were negative relationships for NPY with drinking and restless behavior. Patients' plasma levels of norepinephrine (NE) and epinephrine were slightly elevated, but urinary levels of NE and the serotonin metabolite were markedly increased. Urinary excretion rates for sodium (not potassium), phosphate and especially calcium were decreased in patients even after covarying for less urine production in the ADHD group. NPY levels were inversely related to calcium excretion and drinking was inversely related to circulating sodium. Increases of drinking and circulating NPY in ADHD children and decreased electrolyte excretion may reflect a common disturbance in metabolic homeostasis.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Calcium; Catecholamines; Child; Drinking; Electrolytes; Epinephrine; Female; Humans; Male; Neuropeptide Y; Norepinephrine; Phosphates; Potassium; Sodium