Increased risk of attention-deficit/hyperactivity disorder in adolescents with high salivary levels of copper, manganese, and zinc.

Exposure to toxic heavy metals has been associated with the development of attention-deficit/hyperactivity disorder (ADHD). However, fewer studies have examined the associations between abnormal levels of essential trace metals and ADHD, and none have done so using saliva. We investigated whether salivary metals were associated with ADHD in adolescents aged 12 from the Family Life Project (FLP) using a nested case-control study design that included 110 adolescents who met diagnostic criteria for inattentive (ADHD-I), hyperactive-impulsive (ADHD-H), or combined type ADHD (ADHD-C) (cases) and 173 children who did not (controls). We used inductively coupled plasma optical emission spectrophotometry to measure chromium, copper, manganese, and zinc in saliva samples. We employed logistic regression models to examine associations between quartile levels of individual metals and ADHD outcomes by subtype. Salivary copper levels were significantly associated with increased odds of any ADHD diagnosis (OR = 3.31, 95% CI: 1.08-10.12; p = 0.04) and with increased odds of ADHD-C diagnosis (OR = 8.44, 95% CI: 1.58-45.12; p = 0.01). Salivary zinc levels were significantly associated with increased odds of ADHD-C diagnosis (OR = 4.06, 95% CI: 1.21-13.69; p = 0.02). Salivary manganese levels were also significantly associated with increased odds of ADHD-C diagnosis (OR = 5.43, 95% CI: 1.08-27.27, p = 0.04). This is the first study using saliva to assess metal exposure and provide a potential link between salivary levels of copper, manganese, and zinc and ADHD diagnoses in adolescents. Public health interventions focused on metal exposures might reduce ADHD incidence in low-income, minority communities.

Peridontitis as a Risk Factor for Attention Deficit Hyperactivity Disorder: Possible Neuro-inflammatory Mechanisms.

Periodontitis is a condition caused mostly by the creation of a biofilm by the bacterium P. gingivalis, which releases toxins and damages the tooth structure. Recent research studies have reported association between dental health and neuropsychiatric illnesses. Neuroinflammation triggered by the first systemic inflammation caused by the bacterium present in the oral cavities is a plausible explanation for such a relationship. Substantial amount of evidence supports the role of neuroinflammation and dysfunction of the dopaminergic system in the pathology of ADHD (Attention deficit hyperactivity disorders). Recent epidemiological, microbiological and inflammatory findings strengthen that, periodontal bacteria, which cause systemic inflammation can contribute to neuroinflammation and finally ADHD. Although both diseases are characterized by inflammation, the specific pathways and crosslink's between periodontitis and ADHD remain unknown. Here, the authors describe the inflammatory elements of periodontitis, how this dental illness causes systemic inflammation, and how this systemic inflammation contributes to deteriorating neuroinflammation in the evolution of ADHD. Therefore, the aim of this review is to present possible links and mechanisms that could confirm the evidence of this association.

Interindividual and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients With Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Therapeutic drug monitoring is becoming increasingly important in psychiatric therapy, especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, noninvasive procedures, blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects and to analyze intraindividual variation of serum concentration. METHODS: Thirty-six patients with ADHD (27 children and 9 adults) on MPH medication were included for drug analysis. MPH and its major metabolite ritalinic acid were quantified using liquid chromatography-tandem mass spectrometry measurements. The following correlations were investigated: (1) between drug concentrations in serum and saliva, and (2) between pH value and saliva to serum concentration ratio. Furthermore, the mean intraindividual MPH-concentration fluctuation in saliva under constant frame conditions was analyzed. RESULTS: After quantification, MPH concentrations were approximately 5 times higher in the saliva than in the serum, whereas the concentrations of ritalinic acid were much lower in saliva. We found significant correlations between concentrations of MPH in serum and saliva (r = 0.51, P < 0.05). Saliva MPH measures, compared with serum, were pH-dependent (r = -0.56, P < 0.01). Daily coefficient of variance of saliva concentration in children taking constant medication was 27.3% (11%-42%), whereas the coefficient of variance for the ratio of saliva to serum was 122% (2%-2060%). CONCLUSIONS: Our data indicate that the interindividual variation in saliva to serum concentrations is rather high, whereas the intraindividual variation is fairly low, as already shown in the literature for repeated citalopram serum measurements. Saliva may well serve as an alternative matrix for therapeutic drug monitoring of MPH in patients with ADHD, especially for follow-up examinations. Future research should focus on analyzing the relationship between drug levels in saliva and clinical effects as well as on understanding the mechanisms that generate saliva drug concentrations. These are essential steps before potential clinical use.

Child sex moderates the relationship between cortisol stress reactivity and symptoms over time.

BACKGROUND: Past work suggests that individual differences in stress reactivity have implications for the development of psychopathology; in particular, females' stress reactivity appears more closely tied to internalizing symptoms than males' reactivity. Conversely, males who are under-reactive to threat may be at risk for externalizing problems. However, little is known about when such differences may emerge, although this knowledge could have implications for early prevention. METHODS: Cortisol reactivity to a laboratory stressor was assessed in 409 three-year-old children (201 boys), along with parent-reported children's internalizing (anxiety and depression) and externalizing (oppositional-defiant and attention problems and hyperactivity) symptoms. Parent-reported symptoms were re-collected at child ages 5 (N = 379) and 8 (N = 364). Multilevel modelling was used to investigate whether the relationship between cortisol reactivity and symptoms differed between boys and girls over time. RESULTS: Girls with lower cortisol reactivity showed a negative association between depressive symptoms and time, while girls with higher reactivity showed no such association. No interaction between sex and cortisol reactivity was found for anxious symptoms. Boys with higher cortisol reactivity showed a negative association between symptoms and time, while boys with lower cortisol reactivity showed no such association. Time and ADHD symptoms were unrelated for boys, regardless of their cortisol reactivity. CONCLUSIONS: Findings suggest that the implications of stress reactivity indexed via cortisol vary for boys and girls, as well as for different symptom manifestations.

Does Methylphenidate Reduce Testosterone Levels in Humans? A Prospective Study in Children with Attention-Deficit/Hyperactivity Disorder.

Background: Animal studies and case reports have suggested that methylphenidate exerts adverse effects on gonadal hormones. This study aimed to determine whether methylphenidate alters testosterone levels in children with attention-deficit/hyperactivity disorder through comparison of those with or without methylphenidate treatment. Methods: This 4-week, nonrandomized, prospective study conducted in Taiwan included 203 attention-deficit/hyperactivity disorder patients with a mean age of 8.7 years (boys: 75.8%). After the initial recruitment, 137 received daily methylphenidate treatment (medicated group) and 66 were assessed through naturalistic observation (nonmedicated group). The saliva samples of attention-deficit/hyperactivity disorder patients were used to quantify testosterone levels at baseline and the endpoint by using the chemiluminescence immunoassay. At the 4th week, 86 patients in the medicated group and 46 patients in the nonmedicated group were eligible for statistical analyses. Results: During the study period, salivary testosterone levels did not significantly change in the medicated group (P=.389) or in the nonmedicated group (P=.488). After correction for the potential confounding effects of age and sex, salivary testosterone levels still remained unchanged in the medicated and nonmedicated groups during the 4-week follow-up. In the medicated group, changes in salivary testosterone levels over 4 weeks were not significantly correlated with the methylphenidate daily dose (mean daily dose: 18.1 mg). Conclusions: Findings suggest that short-term treatment with methylphenidate at usual doses does not significantly alter salivary testosterone levels in attention-deficit/hyperactivity disorder patients. Future studies should clarify whether long-term methylphenidate treatment disrupts testosterone production as well as the function of the reproductive system.

The aetiological association between the dynamics of cortisol productivity and ADHD.

Attention-deficit/hyperactivity disorder (ADHD) has been linked to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, indexed by salivary cortisol. The phenotypic and aetiological association of cortisol productivity with ADHD was investigated. A selected twin design using 68 male twin-pairs aged 12-15, concordant or discordant for high ADHD symptom scores, or control twin-pairs with low ADHD symptoms, based on developmentally stable parental ADHD ratings. A genetic growth curve model was applied to cortisol samples obtained across three points during a cognitive-electroencephalography assessment, to examine the aetiological overlap of ADHD affection status (high versus low ADHD symptom scores) with latent intercept and slope factors. A significant phenotypic correlation emerged between ADHD and the slope factor, with cortisol levels dropping faster for the group with high ADHD symptom scores. The analyses further suggested this overlap was mostly driven by correlated genetic effects. We identified change in cortisol activity over time as significantly associated with ADHD affection status, primarily explained by shared genetic effects, suggesting that blunted cortisol productivity can be a marker of genetic risk in ADHD.

Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2.

BACKGROUND: Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene-environment interactions. We conducted an initial examination of CpG methylation variation in children with or without attention-deficit/hyperactivity disorder (ADHD). METHODS: Children age 7-12 were recruited, screened, evaluated and assigned to ADHD or non-ADHD groups by defined research criteria. Two independent age-matched samples were examined, a discovery set (n = 92, all boys, half control, half ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5-methylcytosine levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation array. Genes for which multiple probes were nominally significant and had a beta difference of at least 2% were evaluated for biological relevance and prioritized for confirmation and sequence validation. Gene pathways were explored and described. RESULTS: Two genes met the criteria for confirmation testing, VIPR2 and MYT1L; both had multiple probes meeting cutoffs and strong biological relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were confirmed through bisulfite sequencing. Enrichment analysis suggested involvement of gene sets or pathways related to inflammatory processes and modulation of monoamine and cholinergic neurotransmission. CONCLUSIONS: Although it is unknown to what extent CpG methylation seen in peripheral tissue reflect transcriptomic changes in the brain, these initial results indicate that peripheral DNA methylation markers in ADHD may be promising and suggest targeted hypotheses for future study in larger samples.

Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder.

BACKGROUND: Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. METHODS: Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. RESULTS: No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). CONCLUSIONS: Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life.

Polymorphisms in the FK506 binding protein 5 gene are associated with attention deficit hyperactivity disorder and diurnal cortisol levels.

AIM: Previous studies have shown an association between childhood attention deficit hyperactivity disorder (ADHD) and a down-regulated hypothalamus-pituitary-adrenal axis (HPA axis) with low diurnal cortisol levels. Given the role of the FK506 binding protein 5 (FKBP5) as an important regulator of the negative feedback system of the HPA axis, we set out to investigate possible associations between single nucleotide polymorphisms (SNPs) in FKBP5 in relation to ADHD and diurnal cortisol levels. METHODS: Children with ADHD (n = 81) and healthy comparisons (n = 88) collected saliva four times during a regular school day for radioimmunoassay analysis of cortisol and for genotyping of five SNPs in FKBP5 (rs9296158, rs1360780, rs9470080, rs7748266 and rs9394309). RESULTS: We found associations between SNP genotypes and ADHD as well as between genotypes and diurnal cortisol levels. One of these SNPs, rs9470080, was significantly associated with both ADHD and lower cortisol levels. CONCLUSION: This study contributes to previous findings on a down-regulated HPA axis in children with ADHD by demonstrating an association between ADHD, lower cortisol levels and SNPs of the FKBP5-gene. The relevance of these findings for the development and shaping of ADHD symptoms needs to be approached in larger samples, preferably also taking stress reactivity into consideration.

The Pressure-Activation-Stress scale in relation to ADHD and cortisol.

The Pressure-Activation-Stress (PAS) scale is a self-report questionnaire for children concerning perceived stress. To explore behavioral and physiological correlates, we investigated if scores discriminate between a group prone to perceive high levels of stress [children with attention-deficit/hyperactivity disorder (ADHD)] and a healthy school sample, and if they are associated with diurnal cortisol levels. The PAS scale was filled in at home by children (11-17 years) with clinically confirmed ADHD (n = 102) and non-affected comparisons (n = 146). Saliva samples were collected four times during a regular school day for radioimmunoassay analysis of cortisol. Subtypes and severity of ADHD symptoms were determined using parental rating scales. Children with ADHD scored higher on the PAS scale than a school sample. The PAS scores were similar over ages in the ADHD group while they increased with age in the healthy group. Female sex was associated with higher stress in both groups but no gender interaction was found. No association was found between PAS scores and cortisol levels in neither group. Children in the ADHD group had a lower ratio of cortisol levels/perceived stress on all sampling occasions, built up both by the higher PAS scores and the lower cortisol levels in children with ADHD. The higher PAS scores in children with ADHD support the validity of the scale. The lack of association between PAS scores and diurnal cortisol levels is intriguing and illustrates the complexity of the stress concept. Stress-related fragility seems to accompany ADHD during childhood.

Functional Gastrointestinal Symptoms in Children with Autism and ADHD: Profiles of Hair and Salivary Cortisol, Serum Leptin Concentrations and Externalizing/Internalizing Problems.

BACKGROUND: Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut-Brain axis (GBA) may mediate these relations. We aimed to assess the prevalence and profile of FGIDs in a clinical sample of children with Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) compared to typically developing children (TD) as well as to investigate possible relations between stress-related biomarkers and internalizing/externalizing problems in children with NDDS. METHODS: In total, 120 children, aged between 4 and 12 years old, formed three groups (N = 40, each): ADHD, ASD and TD. Salivary cortisol, hair cortisol and serum leptin were measured. RESULTS: The ASD group had more FGID problems than the TD group (p = 0.001). The ADHD and ASD groups had higher total internalizing/externalizing problems than the TD group (p < 0.0001, p < 0.0001, p = 0.005, respectively). Children with FGIDs showed more total, internalizing and externalizing problems compared to children without FGIDs (p < 0.0001, p < 0.0001, p = 0.041, respectively). The ADHD group showed lower AUCg values (p < 0.0001), while the hair cortisol was higher for the TD group (p < 0.0001). CONCLUSION: In conclusion, children with NDDs had more FGID symptoms and present higher internalizing and externalizing problems. Children with ADHD and FGIDs had more internalizing problems compared to those without FGIDs. No differences in stress-related biomarkers were shown to differentiate children with NDDs with and without FGIDs. Future prospective studies including a greater number of children may elucidate the biological pathways linking these comorbidities.

Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels.

Attention-deficit hyperactivity disorder (ADHD) in adults is associated with impaired sleep, and it has been postulated that this impairment may contribute to the psychopathology of this common condition. One key driver of sleep/wake cycles is the circadian system, which at the molecular level consists of a series of transcriptional feedback loops of clock genes, which in turn produce endocrine, physiological and behavioural outputs with a near 24 h periodicity. We set out to examine circadian rhythms at the behavioural, endocrine and molecular levels in ADHD. Adults with ADHD as well as age- and sex-matched controls were recruited. Circadian rhythms were measured by means of actigraphy for the determination of gross motor patterns, by self-sampling of oral mucosa for assessment of rhythmic expression of the clock genes BMAL1 and PER2, and by estimation of salivary cortisol and melatonin levels. Actigraphic analysis revealed significant diurnal and nocturnal hyperactivity in the ADHD group, as well as a significant shorter period of best fit for the locomotor circadian rhythm in ADHD. BMAL1 and PER2 showed circadian rhythmicity in controls with this being lost in the ADHD group. Cortisol rhythms were significantly phase delayed in the ADHD group. These findings indicate that adult ADHD is accompanied by significant changes in the circadian system, which in turn may lead to decreased sleep duration and quality in the condition. Further, modulation of circadian rhythms may represent a novel therapeutic avenue in the management of ADHD.

Early psychosocial adversity and cortisol levels in children with attention-deficit/hyperactivity disorder.

Previous studies suggest a different regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis) with lower diurnal cortisol levels, especially in the morning, in children with attention-deficit/hyperactivity disorder (ADHD) compared with controls. Since exposure to foetal and childhood psychosocial adversity has been associated with both ADHD and HPA-axis functioning, such exposures may explain these low cortisol levels in ADHD via early programming of the HPA-axis. Thus, our main aim was to retrospectively study foetal and early childhood exposures to psychosocial adversity in children with ADHD and to relate these exposures to cortisol levels. Saliva samples were collected during a regular weekday in children, 6-17 years old, with clinically confirmed ADHD (n = 197) and non-affected comparisons (n = 221) for radioimmunoassay analysis of cortisol. Parental rating scales were used for categorising subtypes of ADHD and degree of exposure to adversity. Children with ADHD had more reports of at least one rated foetal adversity (p = 0.041) and childhood adversity (p < 0.001) than comparisons. The association between low morning cortisol levels and ADHD-symptoms remained when analyses were adjusted for adversities, age, sex, sampling time and symptoms of oppositional defiant disorder. No relation was found between exposures to foetal/childhood adversity and cortisol levels except for a positive relation between childhood adversity and cortisol morning increase in children with ADHD. The hypothesis that early adversity may influence the HPA-axis, leading to lower cortisol levels in children with ADHD, was not supported by our findings.

Altered biochemical parameters in saliva of pediatric attention deficit hyperactivity disorder.

Oxidative stress is one of the common causes in etiopathogenesis of attention deficit hyperactivity disorder (ADHD). Hence, the salivary levels of protein thiols, ceruloplasmin, magnesium and pseudocholinesterase were estimated in children with ADHD. The symptoms of ADHD were identified using Conner's rating and DSM IV criteria. Saliva was collected and assessed for the levels of protein thiols, ceruloplasmin, magnesium and pseudocholinesterase, spectrophotometrically. It was also checked for pH and the flow rate was noted down. There was a significant increase (P < 0.001) in the salivary protein thiols and pseudocholinesterase levels in ADHD children when compared to controls. Ceruloplasmin levels did not show any significant change. Magnesium levels were significantly decreased (P < 0.001) in cases when compared to controls. Further, a receiver operating characteristic curve for validity of the biochemical parameters in saliva of ADHD children indicated a sensitivity and specificity above 90% for protein thiols and magnesium values. Our study shows that protein thiols, magnesium, and pseudocholinesterase might have a role in the pathogenesis of ADHD and saliva can be effectively used as a non-invasive tool for evaluation of such children.

Salivary cortisol responsivity to an intravenous catheter insertion in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To compare salivary cortisol baseline levels and responsivity as well as behavioral distress to intravenous (IV) catheter insertions in 4- to 10-year-old children with (n = 29) and without (n = 339) attention-deficit/hyperactivity disorder (ADHD). METHODS: This is a secondary data analysis from a sample of 542 children who participated in a multisite study on distraction. Data included were demographic variables, Pediatric Behavior Scale-30, Observational Scale of Behavioral Distress-Revised, and four salivary cortisol samples. RESULTS: Home samples from the ADHD group revealed nonsignificant but higher cortisol levels than the non-ADHD group. However, on the clinic day, the ADHD group had significantly lower cortisol levels before (0.184 vs. 0.261, p = .040) and 20-30 min after IV insertion (0.186 vs. 0.299, p = .014) compared with the non-ADHD group. CONCLUSIONS: Cortisol levels in children with and without ADHD differ in response to the stress of an IV insertion.

Circadian rhythms of saliva melatonin in ADHD, anxious and normal children.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders are the most frequent psychiatric disorders in children. Changes in rhythms of symptoms during the day may be influenced by genetic, biological and psychological factors. Some changes of melatonin rhythm may hypothetically change the activity of ADHD by changing arousal or in anxiety children by changing their emotional state. In our present study we identify one group of ADHD children combine type without comorbids, one group of anxiety children and a control group. Most changes of melatonin daily rhythm are supposed in the anxiety group, especially in sleeping time, and more prominent change in the ADHD group with prominent hyperactivity and conduct disorder symptoms. METHODS: Thirty-four ADHD and forty-three control children and eleven anxiety children, all 6-12 years old, participated in the study. The saliva specimens were collected in four different sessions during the school year, around the time of the spring and autumn equinox, when the natural light lasted 11.2 h ± 0.9 h. RESULTS AND CONCLUSIONS: In our study more symptoms of conduct disorder elevated positive or negative correlations between psychopathology and saliva level of melatonin in ADHD and anxiety samples. We hypothesize that co-morbidity of ADHD or anxiety with impulsivity and conduct disorders might have elevated correlations between psychopathology of ADHD or anxiety and plasma melatonin level.

Lack of association between severity of ADHD symptoms and salivary oxytocin levels.

Impairments in the reactivity of Oxytocin (OT) system were associated with interpersonal difficulties in children with ADHD. The current study aimed to explore the correlation between symptoms severity and salivary OT levels at different time-points in children with ADHD. Symptoms severity was assessed in 50 children with ADHD (28 males, mean age 9.42 ± 1.65) using the Swanson, Nolan and Pelham Questionnaire-IV (SNAP-IV) and the Strengths and Difficulties Questionnaire (SDQ). Salivary OT levels were measured at baseline, as well as 15 min after positive social interaction. There was no statistical correlation between severity of ADHD and salivary OT levels in each of the time points. We conclude that impairments in the reactivity of the OT system in children with ADHD, associated with interpersonal impairments, might be a distinct aspect of the clinical picture, differentiated from the levels of inattentive, hyperactive/impulsive or behavioral symptoms.

Does the cortisol response to stress mediate the link between expressed emotion and oppositional behavior in Attention-Deficit/Hyperactivity-Disorder (ADHD)?

BACKGROUND: Expressed Emotions (EE) are associated with oppositional behavior (OPB) in children with Attention Deficit/Hyperactivity Disorder (ADHD). EE has been linked to altered stress responses in some disorders, but ADHD has not been studied. We test the hypothesis that OPB in ADHD is mediated by altered stress-related cortisol reactivity to EE. METHODS: Two groups of children (with/without ADHD) and their respective parents were randomly assigned to two different conditions with/without negative emotion and participated in an emotion provocation task. Parents' EE, their ratings of their children's OPB and their children's salivary cortisol levels were measured. RESULTS: Low parental warmth was associated with OPB in ADHD. High levels of parental EE elicited a larger cortisol response. Stress-related cortisol reactivity mediated the EE-OPB link for all children. This highlights the general importance of parent-child interactions on externalizing behavior problems. CONCLUSION: High EE is a salient stressor for ADHD children that leads to increased levels of cortisol and OPB. The development of OPB might be mediated by the stress-response to high EE.

Lower strontium in two different body matrices in neurodevelopmental disorders: A preliminary report.

BACKGROUND: Environmental factors, including elemental homeostasis, have not been studied sufficiently in neurodevelopmental disorders (NDD). This study aims to compare the status of 13 elements in blood and deciduous teeth dentine of children having an autism spectrum disorder or attention deficit hyperactivity disorder with typically developing controls. METHODS: Elements including calcium, phosphorus, magnesium, iron, zinc, copper, chromium, manganese, mercury, lead, cadmium, molybdenum, and strontium in both deciduous teeth and blood were analyzed by inductively coupled plasma mass spectrometry. RESULTS: Strontium levels in both blood and teeth samples were found to be significantly lower in the NDD group. Additionally, blood cadmium and mercury levels, and copper/zinc ratio were higher in the NDD group. CONCLUSIONS: Our results warrant further investigation in a large series of NDD examining symptom levels and genetic variations associated with elemental homeostasis.

The effect of methylphenidate on social cognition and oxytocin in children with attention deficit hyperactivity disorder.

The current study aimed to explore the possible effect of stimulants on oxytocin (OT), a neuropeptide which regulates social behavior, as a mediator of the pro-social effect of methylphenidate (MPH) in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls (HCs). Utilizing a double-blind placebo-controlled design, we compared the performance of 50 children with ADHD and 40 HCs in "theory of mind" (ToM) tasks and examined the effect of a single dose of MPH/placebo on ToM and salivary OT levels in children with ADHD at baseline and following an interpersonal interaction. Children with ADHD displayed significantly poorer ToM performance; however, following MPH administration, their performance normalized and differences between children with ADHD and HC were no longer found. Salivary OT levels at baseline did not differ between children with ADHD and HCs. However, after a parent-child interaction, OT levels were significantly higher in the HC group compared to children with ADHD. Administration of MPH attenuated this difference such that after parent-child interaction differences in OT levels between children with ADHD and HC were no longer found. In the ADHD group, OT levels decreased from administration of placebo to the parent-child interaction. However, the administration of MPH to children with ADHD was associated with an increase in OT levels after the parent-child interaction. We conclude that OT might play a role as a mediator of social deficits in children with ADHD and that the reactivity of the OT system to social interaction in children with ADHD might be impaired. Stimulants may improve ToM and social functions in children with ADHD via its impact on the OT system. PRS: OT and Social Cognition in Children with ADHD: Impact of MPH.