Quantitative susceptibility mapping shows lower brain iron content in children with attention-deficit hyperactivity disorder.

To investigate the feasibility of quantitative susceptibility mapping in children with attention-deficit hyperactivity disorder (ADHD), 53 children with ADHD aged 5-16 years were prospectively selected as the study group and 49 healthy children matched with age and gender were selected as the control group. All children underwent magnetic resonance imaging conventional sequence, 3D-T1, and enhanced T2*-weighted magnetic resonance angiography (ESWAN) sequence scanning. The iron content of brain regions was obtained through software postprocessing, and the iron content of brain regions of children with ADHD and healthy children was compared and analyzed to find out the characteristics of the iron content of brain regions of children with ADHD. The iron content in frontal lobe, globus pallidus, caudate nucleus, substantia nigra, putamen, and hippocampus of children with ADHD was lower than that of healthy children (p < .05). There was no significant difference in the content of iron in the left and right brain regions of children with ADHD (p > .05). The volume of frontal lobe and hippocampus of children with ADHD was lower than that of healthy children (p < .05). Iron content in brain areas such as globus pallidus, caudate nucleus, hippocampus, and putamen could distinguish children with ADHD (Area under curve [AUC] > 0.5, p < .05). Quantitative susceptibility mapping showed decreased iron content in some brain regions of children with ADHD.

Early detection and treatment of attention deficits in preterm and at term infants with risk factors for brain damage.

Cognitive deficits in infants born preterm and infants at term with risk factors for brain damage are a common outcome. Attention deficits in preterm infants are related to the development of attention-deficit/hyperactivity disorder (ADHD), and therefore, there is a need for earlier evaluations and treatment procedures that are implemented before the presence of signs of ADHD. METHODS: We studied preterm (74%) and term infants with the Infant Scale of Selective Attention (ISSA, Escala de Evaluación de la Atención Selectiva (EEAS), in Spanish). This scale evaluates both visual- and auditory-orienting attention. Two groups participated, one with attention deficits (n = 26) and another with regular performance (n = 36). An early attention-stimulation program (EASP) was implemented in the infant group with attention deficits from three to eight months of age. All infants underwent magnetic resonance imaging (MRI), and visual and auditory evoked responses were assessed. RESULTS: All infants had prenatal and perinatal risk factors for brain damage and abnormal MRI findings, and the majority had abnormalities compatible with white matter injury. However, there were four infants with porencephalic cysts; 3 of them were in the treated group. At the beginning of the treatment, ISSA values showed differences between groups. These differences persisted for five months in the visual test and up to the sixth month in the auditory evaluation. Afterward, there were no significant differences, indicating that infants with attention deficits had satisfactorily responded to the treatment. CONCLUSIONS: The ISSA is helpful for the early evaluation of visual and auditory attention. Infants with attention deficits react well enough after six months of EASP.

Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD).

Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1-8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults-the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.

Alternations in nuclear factor kappa beta activity (NF-kB) in the rat brain due to long-term use of atomoxetine for treating ADHD: In vivo and in silico studies.

Attention Deficit Hyperactivity Disorder (ADHD) is the most common psychiatric disorder reported particularly in children. Long-term use of antipsychotic drugs used in the treatment of ADHD has been shown to exert toxic effects on the brain. However, not enough research has been carried out on the neurotoxic effects of these drugs on the brain tissue. Atomoxetine (ATX) is the most widely used antipsychotic drug that has gained approval for ADHD treatment. The present study aims to determine the damage induced by long-term use of three different doses of ATX in the brain tissue of experimental rats. 24 rats were divided into Control group (0.5 mL saline), Group 2 (0.5 mg/mL ATX), Group 3 (1.0 mg/mL ATX), and Group 4 (2.0 mg/mL ATX), each group having 6 members. Their brain tissues were taken for stereological, histological, and nuclear factor kappa-B (NF-kB) protein expression analysis. ATX was determined to have caused a few alterations in the brain tissue, such as disruption in the endothelial epithelium of capillaries, a couple of large astrocyte nuclei, and mitotic astrocytes. Moreover, a significant difference was observed in Group 4 compared to Control Group in terms of astrocyte counts in the brain sections. As for Groups 3 and 4, there were differences in terms of oligodendrocyte counts in the incisions cultivated from the brain tissues of the animals. On the other hand, NF-kB positive astrocytes of Groups 3 and 4 differed significantly from those of Control and Group 2. The results of molecular dockings of the present study are in line with the in-vivo results. Therefore, it was concluded that the higher the dose of ATX was, the more damage the brain tissue sustained.

Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD. METHODS: We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework. RESULTS: Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration. CONCLUSIONS: Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs. REGISTRATION: PROSPERO no. CRD 42015026049.

Assessment of intraocular pressure, macular thickness, retinal nerve fiber layer, and ganglion cell layer thicknesses: ocular parameters and optical coherence tomography findings in attention-deficit/hyperactivity disorder

Objective: To compare intraocular pressure (IOP) and macular, retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thicknesses in treatment-naive children with attention-deficit/hyperactivity disorder (ADHD), children with ADHD on regular methylphenidate (MPH) treatment for at least 3 months, and healthy controls. Methods: A total of 58 treatment-naive children with ADHD, 45 children with ADHD on regular MPH treatment, and 44 healthy controls were enrolled in this study. All participants underwent a comprehensive eye examination. Optical coherence tomography (OCT) was used to assess global RNFL thickness, central macular thickness, and GCL thickness in both eyes. Results: Separate univariate analysis of covariance (ANCOVA) on the outcome variables revealed a significant difference among the research groups with respect to IOP in the left eye. Post-hoc univariate analyses indicated that left IOP was significantly higher in children with ADHD under MPH treatment than among healthy controls. However, global RNFL thickness, central macular thickness, and GCL thickness of both eyes, as well as IOP in the right eye, were not significantly different across groups. Conclusion: Further longitudinal follow-up studies are needed to determine whether MPH treatment has any effect on IOP or OCT findings.

Caffeine and adenosine A2A receptors rescue neuronal development in vitro of frontal cortical neurons in a rat model of attention deficit and hyperactivity disorder.

Although some studies have supported the effects of caffeine for treatment of Attention deficit and hyperactivity disorder (ADHD), there were no evidences about its effects at the neuronal level. In this study, we sought to find morphological alterations during in vitro development of frontal cortical neurons from Spontaneoulsy hypertensive rats (SHR, an ADHD rat model) and Wistar-Kyoto rats (WKY, control strain). Further, we investigated the effects of caffeine and adenosine A1 and A2A receptors (A1R and A2AR) signaling. Cultured cortical neurons from WKY and SHR were analyzed by immunostaining of microtubule-associated protein 2 (MAP-2) and tau protein after treatment with either caffeine, or A1R and A2AR agonists or antagonists. Besides, the involvement of PI3K and not PKA signaling was also assessed. Neurons from ADHD model displayed less neurite branching, shorter maximal neurite length and decreased axonal outgrowth. While caffeine recovered neurite branching and elongation from ADHD neurons via both PKA and PI3K signaling, A2AR agonist (CGS 21680) promoted more neurite branching via PKA signaling. The selective A2AR antagonist (SCH 58261) was efficient in recovering axonal outgrowth from ADHD neurons through PI3K and not PKA signaling. For the first time, frontal cortical neurons were isolated from ADHD model and they presented disturbances in the differentiation and outgrowth. By showing that caffeine and A2AR may act at neuronal level rescuing ADHD neurons outgrowth, our findings strengthen the potential of caffeine and A2AR receptors as an adjuvant for ADHD treatment.

Cingulate impairments in ADHD: Comorbidities, connections, and treatment.

The entire cingulate cortex is engaged in the structure/function abnormalities found in attention-deficit/hyperactivity disorder (ADHD). In ADHD, which is the most common developmental disease, impaired impulse control and cognition often trace to anterior midcingulate cortex (aMCC) in Go/No-go tests, decoding and reading, the Stroop Color and Word Test, and the Wisconsin Card Sorting Test (WCST), with volume deficits in anterior cingulate cortex (ACC) and posterior midcingulate cortex (pMCC). Volumes in pMCC correlate positively with the WCST and negatively with total and nonperseverative errors on the WCST. Activation and connectivity on N-back tests show connections for high and low spatial working memory, but patients have increased activation in PCC and decreased connectivity between MCC and PCC for high load. Students struggle in class due to malfunctioning aMCC, pregenual anterior cingulate cortex (pACC), and dorsal posterior cingulate cortex (dPCC), and to core deficits in response/task switching in aMCC. Gene mutations are found in the DA transporter and DA4 and DA5 receptors. Methylphenidate decreases hyperactivity in aMCC. The DA system is controlled by cholinergic receptors in the daMCC and genetics show nAChR mutations in alpha 3, 4, and 7 receptors. At 25 years, a modified Eriksen flanker/No-go task and voxel-based morphometry (VBM) show prenatal smoking, lifetime smoking at 13 years, and novelty seeking. Prenatal exposure to nicotine exhibits weaker responses in aMCC during cognitive tasks for hyperactivity/impulsiveness but not inattention. AZD1446 (ɑ4ß2 nAChR agonist) improves the Groton Maze task due to high nAChR in dPCC/RSC engaged in spatial orientation. Environmental factors associated with childhood ADHD relate to pesticides, organochlorine, and air pollutants. Network connection segregation shows increased amygdala local nodal, but decreased ACC and PCC connections, reflecting emphasis on local periamygdala connections at the expense of cortical connections. Thus, ADHD children/adolescents respond impulsively to the significance of stimuli without having cortical inhibition. Finally, controls show negative relationships between aMCC and the default mode network, and ADHD compromises this relationship, showing decreased connectivity between ACC and precuneus/PCC.

Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. METHODS: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection. Neurocognitive testing included measures of attention and executive function. fMRI was obtained during completion of two tasks, the continuous performance task (CPT) and the attention network task (ANT). Image analysis was performed using Statistical Parametric Mapping software, with contrasts targeting sustained attention, alerting, orienting, and conflict. All statistical tests were two-sided. RESULTS: Compared with population norms, survivors demonstrated impairment on number-letter switching (P < .001, a measure of cognitive flexibility), which was associated with treatment intensity (P = .048). Task performance during fMRI was associated with neurocognitive dysfunction across multiple tasks. Regional brain activation was lower in survivors diagnosed at younger ages for the CPT (bilateral parietal and temporal lobes) and the ANT (left parietal and right hippocampus). With higher serum methotrexate exposure, CPT activation decreased in the right temporal and bilateral frontal and parietal lobes, but ANT alerting activation increased in the ventral frontal, insula, caudate, and anterior cingulate. CONCLUSIONS: Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors.

The KCNH3 inhibitor ASP2905 shows potential in the treatment of attention deficit/hyperactivity disorder.

N-(4-fluorophenyl)-N'-phenyl-N"-(pyrimidin-2-ylmethyl)-1,3,5-triazine-2,4,6-triamine [ASP2905] is a potent and selective inhibitor of the potassium voltage-gated channel subfamily H member 3 (KCNH3) that was originally identified in our laboratory. KCNH3 is concentrated in the forebrain, and its overexpression in mice leads to cognitive deficits. In contrast, Kcnh3 knockout mice exhibit enhanced performance in cognitive tasks such as attention. These data suggest that KCNH3 plays important roles in cognition. Here we investigated the neurochemical and neurophysiological profiles of ASP2905 as well as its effects on cognitive function, focusing on attention. ASP2905 (0.0313 and 0.0625 mg/kg, po) improved the latent learning ability of mice, which reflects attention. Microdialysis assays in rats revealed that ASP2905 increased the efflux of dopamine and acetylcholine in the medial prefrontal cortex (0.03, 0.1 mg/kg, po; 0.1, 1 mg/kg, po, respectively). The activities of these neurotransmitters are closely associated with attention. We used a multiple-trial passive avoidance task to investigate the effects of ASP2905 on inattention and impulsivity in juvenile stroke-prone spontaneously hypertensive rats. ASP2905 (0.1 and 0.3 mg/kg, po) significantly prolonged cumulative latency as effectively as methylphenidate (0.1 and 0.3 mg/kg, sc), which is the gold standard for treating ADHD. Further, ASP2905, amphetamine, and methylphenidate significantly increased the alpha-band power of rats, suggesting that ASP2905 increases arousal, which is a pharmacologically important activity for treating ADHD. In contrast, atomoxetine and guanfacine did not significantly affect power. Together, these findings suggest that ASP2905, which acts through a novel mechanism, is as effective for treating ADHD as currently available drugs such as methylphenidate.

Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics.

PURPOSE: The aim of this study was to evaluate maternal, prenatal, perinatal, and postpartum parameters as risk factors for the later development of an attention deficit hyperactivity disorder (ADHD) in the child. METHODS: Women who had given birth at Erlangen University Hospital between 1996 and 1999 were sent a questionnaire in 2009. The results of the questionnaire were correlated with the prospectively collected data for the births in 1996-1999. RESULTS: A total of 573 mother and child pairs were analyzed. Forty-four of the mothers reported that their child had ADHD (7.7%). No significant associations were found for the following parameters: mother's age; mother's educational level; number of the pregnancy; maternal weight before and at the end of pregnancy; mother's height; alcohol consumption during pregnancy; mode of delivery; gestational week; birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower than 7 after 1 min were significantly associated with a risk for later development of ADHD. CONCLUSIONS: This analysis of maternal, prenatal, perinatal, and postnatal parameters found that smoking in pregnancy and a low Apgar score 1 min after birth are associated with a significantly greater risk for the development of ADHD. Beyond the question of the causal mechanism involved, this is a relevant finding, since smoking during pregnancy is a preventable risk factor.

Attention and working memory deficits in a perinatal nicotine exposure mouse model.

BACKGROUND: Cigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. Here we describe behavioral phenotypes resulting from perinatal nicotine exposure in a mouse model, and discuss our findings in the context of findings from previously published studies using preclinical models of developmental nicotine exposure. METHODOLOGY/PRINCIPAL FINDINGS: Female C57Bl/6 mice received drinking water containing nicotine (100µg/ml) + saccharin (2%) starting 3 weeks prior to breeding and continuing throughout pregnancy, and until 3 weeks postpartum. Over the same period, female mice in two control groups received drinking water containing saccharin (2%) or plain drinking water. Offspring from each group were weaned at 3-weeks of age and subjected to behavioral analyses at 3 months of age. We examined spontaneous locomotor activity, anxiety-like behavior, spatial working memory, object based attention, recognition memory and impulsive-like behavior. We found significant deficits in attention and working memory only in male mice, and no significant changes in the other behavioral phenotypes in male or female mice. Exposure to saccharin alone did not produce significant changes in either sex. CONCLUSION/SIGNIFICANCE: The perinatal nicotine exposure produced significant deficits in attention and working memory in a sex-dependent manner in that the male but not female offspring displayed these behaviors. These behavioral phenotypes are associated with attention deficit hyperactivity disorder (ADHD) and have been reported in other studies that used pre- or perinatal nicotine exposure. Therefore, we suggest that preclinical models of developmental nicotine exposure could be useful tools for modeling ADHD and related disorders.

Generation of a human induced pluripotent stem cell (iPSC) line from a 51-year-old female with attention-deficit/hyperactivity disorder (ADHD) carrying a duplication of SLC2A3.

Fibroblasts were isolated from a skin biopsy of a clinically diagnosed 51-year-old female attention-deficit/hyperactivity disorder (ADHD) patient carrying a duplication of SLC2A3, a gene encoding neuronal glucose transporter-3 (GLUT3). Patient fibroblasts were infected with Sendai virus, a single-stranded RNA virus, to generate transgene-free human induced pluripotent stem cells (iPSCs). SLC2A3-D2-iPSCs showed expression of pluripotency-associated markers, were able to differentiate into cells of the three germ layers in vitro and had a normal female karyotype. This in vitro cellular model can be used to study the role of risk genes in the pathogenesis of ADHD, in a patient-specific manner.

Peripheral iron levels in children with attention-deficit hyperactivity disorder: a systematic review and meta-analysis.

There is growing recognition that the risk of attention-deficit hyperactivity disorder (ADHD) in children may be influenced by micronutrient deficiencies, including iron. We conducted this meta-analysis to examine the association between ADHD and iron levels/iron deficiency (ID). We searched for the databases of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to August 9th, 2017. Primary outcomes were differences in peripheral iron levels in children with ADHD versus healthy controls (HCs) and the severity of ADHD symptoms in children with/without ID (Hedges' g) and the pooled adjusted odds ratio (OR) of the association between ADHD and ID. Overall, seventeen articles met the inclusion criteria. Peripheral serum ferritin levels were significantly lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges' g = -0.246, p = 0.013), but no significant difference in serum iron or transferrin levels. In addition, the severity of ADHD was significantly higher in the children with ID than those without ID (with ID = 79, without ID = 76, Hedges' g = 0.888, p = 0.002), and there was a significant association between ADHD and ID (OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower serum ferritin levels and ID. Future longitudinal studies are required to confirm these associations and to elucidate potential mechanisms.

Thalamic and basal ganglia regions are involved in attentional processing of behaviorally significant events: evidence from simultaneous depth and scalp EEG.

Extensive descriptions exist on cortical responses to change in the acoustic environment. However, the involvement of subcortical regions is not well understood. Here we present simultaneous recordings of cortical and subcortical event-related potentials (ERPs) to different pure tones in patients undergoing surgery for deep brain stimulation (DBS). These patients had externalized electrodes in the subthalamic nucleus (STN), the ventrolateral posterior thalamus (VLp) or the globus pallidus internus (GPi). Subcortical and cortical ERPs were analyzed upon presentation of one frequent non-target stimulus and two infrequent stimuli, either being a target or a distractor stimulus. The results revealed that amplitudes of scalp-recorded P3 and subcortical late attention-modulated responses (AMR) were largest upon presentation of target stimuli compared with distractor stimuli. This suggests that thalamic and basal ganglia regions are sensitive to behaviorally relevant auditory events. Comparison of the subcortical structures showed that responses in VLp have shorter latency than in GPi and STN. Further, the subcortical responses in VLp and STN emerged significantly prior to the cortical P3 response. Our findings point to higher-order cognitive functions already at a subcortical level. Auditory events are categorized as behaviorally relevant in subcortical loops involving basal ganglia and thalamic regions. This label is then distributed to cortical regions by ascending projections.

Deficiency of tumor suppressor NDRG2 leads to attention deficit and hyperactive behavior.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children. Although an imbalance of excitatory and inhibitory inputs has been proposed as contributing to this disorder, the mechanisms underlying this highly heterogeneous disease remain largely unknown. Here, we show that N-myc downstream-regulated gene 2 (NDRG2) deficiency is involved in the development of ADHD in both mice and humans. Ndrg2-knockout (Ndrg2-/-) mice exhibited ADHD-like symptoms characterized by attention deficits, hyperactivity, impulsivity, and impaired memory. Furthermore, interstitial glutamate levels and excitatory transmission were markedly increased in the brains of Ndrg2-/- mice due to reduced astroglial glutamate clearance. We developed an NDRG2 peptide that rescued astroglial glutamate clearance and reduced excitatory glutamate transmission in NDRG2-deficient astrocytes. Additionally, NDRG2 peptide treatment rescued ADHD-like hyperactivity in the Ndrg2-/- mice, while routine methylphenidate treatment had no effect on hyperactivity in these animals. Finally, children who were heterozygous for rs1998848, a SNP in NDRG2, had a higher risk of ADHD than children who were homozygous for rs1998848. Our results indicate that NDRG2 deficiency leads to ADHD phenotypes and that impaired astroglial glutamate clearance, a mechanism distinct from the well-established dopamine deficit hypothesis for ADHD, underlies the resultant behavioral abnormalities.

Effect of tobacco smoking on frontal cortical thickness development: A longitudinal study in a mixed cohort of ADHD-affected and -unaffected youth.

Smoking rates are particularly high during adolescence and young adulthood, when the brain is still undergoing significant developmental changes. Cross-sectional studies have revealed altered brain structure in smokers, such as thinner frontal cortical areas. Attention-deficit/hyperactivity disorder (ADHD) increases the risk of becoming nicotine-dependent, and has also been associated with abnormalities in frontal gray matter structure. The present study examines the relationships between smoking, cortical thickness and ADHD symptoms in a longitudinal design that compares adolescent and young adult smokers (n=44; 35 ADHD-affected) and non-smokers (n=45; 32 ADHD-affected) on frontal cortical thickness. Average frontal cortical thickness was estimated through structural magnetic resonance imaging (MRI) at two time points (mean ages 17.7 and 21.1 years), on average 3.4 years apart. Smokers had a 2.6% thinner frontal cortex than non-smokers and this difference was not explained by ADHD or other confounding factors. The rate of cortical thinning across the 3.4-year MRI measurement interval was similar in the total group of smokers compared to non-smokers. However, speeded thinning did occur in smokers who had started regular smoking more recently, in between the two measurements. These novel regular smokers did not differ significantly from the non-smokers at baseline. This suggests that the thinner frontal cortex was not a predisposing factor but rather a consequence of smoking. Although smokers had more ADHD symptoms overall, smoking did not influence the developmental course of ADHD symptoms.

Response inhibition in Attention deficit disorder and neurofibromatosis type 1 - clinically similar, neurophysiologically different.

There are large overlaps in cognitive deficits occurring in attention deficit disorder (ADD) and neurodevelopmental disorders like neurofibromatosis type 1 (NF1). This overlap is mostly based on clinical measures and not on in-depth analyses of neuronal mechanisms. However, the consideration of such neuronal underpinnings is crucial when aiming to integrate measures that can lead to a better understanding of the underlying mechanisms. Inhibitory control deficits, for example, are a hallmark in ADD, but it is unclear how far there are similar deficits in NF1. We thus compared adolescent ADD and NF1 patients to healthy controls in a Go/Nogo task using behavioural and neurophysiological measures. Clinical measures of ADD-symptoms were not different between ADD and NF1. Only patients with ADD showed increased Nogo errors and reductions in components reflecting response inhibition (i.e. Nogo-P3). Early perceptual processes (P1) were changed in ADD and NF1. Clinically, patients with ADD and NF1 thus show strong similarities. This is not the case in regard to underlying cognitive control processes. This shows that in-depth analyses of neurophysiological processes are needed to determine whether the overlap between ADD and NF1 is as strong as assumed and to develop appropriate treatment strategies.

Effect of adenotonsillectomy on attention deficit-hyperactivity disorder in children with adenotonsillar hypertrophy: A prospective cohort study.

BACKGROUND: This study was conducted to explore the effect of adenotonsillectomy on the improvement of attention deficit hyperactivity disorder (ADHD) symptoms in children with adenotonsillar hypertrophy. METHODS: This prospective cohort study was conducted on 59 children aged 6-12 years with adenotonsillar hypertrophy and ADHD who were candidates for adenotonsillectomy at Besat Hospital, Hamadan University of Medical Sciences, in 2014. The status of ADHD was evaluated at baseline and one and three months after surgery using Conners' Rating Scales. RESULTS: Of 59 children with ADHD (35 boys and 24 girls), 41 improved one month after surgery and 51 after three months. Only 8 children had no improvement. The Conners' score decreased significantly from 71.37 at baseline to 61.31 (P = 0.001) and 49.14 (P = 0.001) one and three months after surgery, respectively. The score of attention deficit and hyperactivity decreased from 1.76 and 2.10 at baseline to 1.52 and 1.83 after one month (P = 0.001) and to 1.24 and 1.52 after three months (P = 0.001), respectively. The results were statistically significant for both boys and girls. CONCLUSION: This study indicated that adenotonsillectomy can significantly improve ADHD in children with adenotonsillar hypertrophy and help them return to normal life.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

BACKGROUND: Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. METHODS: Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. RESULTS: After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. DISCUSSION: Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD.