Exploring the Link between ADHD and Obesity: A Focus on Temperament.

Multiple studies support the relationship between ADHD and overweight/obesity in youth. Different mechanisms may be involved, such as temperamental and psychopathological factors. The aim of this study was to test the hypothesis that specific temperamental and psychopathological dimensions could mediate the relationship between ADHD and obesity. The sample included 100 children and adolescents (78 males and 22 females; age range 6 to 18 years; mean age 9.90 ± 2.5 years). The assessment procedure included Conners' Parent Rating Scale-Long (CPRS-R:L) as the inclusion criterion for ADHD diagnosis, the Child Behavior Checklist (CBCL), a dimensional measure for psychopathology, and the Junior Temperament and Character Inventory, which describes four temperamental dimensions: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (P). While in the whole ADHD sample, the highest scores were found in NS and the lowest in P, ADHD with overweight/obesity, compared to ADHD with normal weight, showed higher HA and RD, lower NS, and higher CBCL Internalizing scores. These findings suggest that ADHD youth with overweight/obesity present specific temperamental and psychopathological features compared to those without overweight/obesity. If confirmed in larger samples, using a control group without ADHD, these temperamental and psychological features may be helpful for an earlier recognition of ADHD patients at higher risk for obesity, and may represent possible targets for temperament-based preventive interventions and tailored treatment programs. These features should be included in the routine assessment of children and adolescents with ADHD and/or are overweight/obese.

Parental Stress and Disability in Offspring: A Snapshot during the COVID-19 Pandemic.

Parenting a child with a disability, such as neurodevelopmental disorders and genetic syndromes, implies a high level of stress. During the COVID-19 outbreak-as a period implying additional challenges-few studies have specifically investigated caregivers' distress among neurodevelopmental disabilities. The objective of the study is to investigate whether during the COVID-19 pandemic, the level of parental stress differs between four disability groups including neurodevelopmental disorders (autism spectrum disorder (ASD), attention deficit and hyperactivity disorder (ADHD)) and genetic syndromes (Rett syndrome (RTT), Sotos syndrome (SS)) in comparison to families with typical development offspring (TD). In total, 220 Italian parents of children affected by neurodevelopmental disabilities (74 ASD, 51 ADHD, 34 SS, 21 RTT, 40 TD; age M 9.4 ± SD 4.2) underwent a standardized evaluation for stress related to parenting through the self-report questionnaire, Parental Stress Index-Short Form (PSI-SF). The main findings show greater levels of parental stress-mainly linked to child behavioral characteristics rather than parental sense of competence-in parents of children affected by a disability in comparison to children with typical development. This study highlights the need to support not only individuals with special needs but also their own caregivers: core figures in the management and outcome of children disorders.

Can melatonin prevent or improve metabolic side effects during antipsychotic treatments?

In the last two decades, second-generation antipsychotics (SGAs) were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs) can cause several sleep disorders, and circadian misalignment can influence hormones involved in the metabolic regulation, such as insulin, leptin, and ghrelin; furthermore, a relationship between obesity and sleep curtailment has been demonstrated, as well as sleep deprivation in rats has been associated with hyperphagia. Metabolic effects of melatonin, both central and peripheral, direct and indirect, target most metabolic disorders reported during and after SGA treatment in children, adolescents, and adults. Further systematic studies on psychiatric patients are needed to explore the effect of add-on melatonin on metabolic side effects of SGAs, independent of energy intake, diet, and exercise.

Might the temperament be a bias in clinical study on attention-deficit hyperactivity disorder (ADHD)?: Novelty Seeking dimension as a core feature of ADHD.

Some clinical studies on attention deficit hyperactivity disorder (ADHD) have been found to overlap those of studies on personality, particularly those on the Novelty Seeking trait (NS) as measured by the Junior Temperament and Character Inventory (JTCI). The aim of this study was to evaluate the potential role of NS in clinical research on ADHD. We enroled 146 ADHD children (125 boys; mean age=9.61, S.D.=2.50) and 223 age- and gender-matched control children (178 boys; mean age=9.41, S.D.=2.30). All the parents filled in the JTCI for the evaluation of personality according to Cloninger׳s model. An exploratory factor analysis differentiated the NS items that concern "Impulsivity" (NS1) from those that concern other features (NS2). Multivariate Analysis of Variance (MANOVAs) revealed significant differences between ADHD children and non-ADHD children in temperamental dimensions: the scores of ADHD children were higher than those of non-ADHD children in Total NS, NS1-Impulsivity and NS2. Our results show that the NS dimension of the JTCI in ADHD children is higher than in non-ADHD children, even when a correction is made for impulsivity items. This finding suggests that the NS trait plays a central role in ADHD diagnosis even when items referred to impulsivity are removed from the NS scale.

Role of ADHD symptoms as a contributing factor to obesity in patients with MC4R mutations.

Besides the crucial role of genetic susceptibility in the development of early-onset obesity, it has been shown that feeding behavior could contribute to increased body weight. A significant association between obesity/overweight and ADHD has been reported, suggesting that these two conditions, despite their heterogeneity, might share common molecular pathways. Although the co-occurrence of obesity and ADHD is increasingly supported by empirical evidence, the complex pathogenetic link between these two conditions is still unclear. Here, we focus on the relationship between MC4R gene mutations and ADHD in children with early-onset obesity. Mutations in the gene MC4R lead to the most common form of monogenic obesity. We hypothesize that dysregulated eating behavior in a subset of patients with MC4R mutation might be due to comorbid ADHD symptoms, underpinned by abnormal reward mechanisms. Therefore, we speculate that it is possible to prevent obesity in a subset of patients with MC4R mutation, even if these patients are genetically programmed to "be fat", via an appropriate treatment of ADHD symptoms. We hope that our paper will stimulate further studies testing if the early screening for ADHD symptoms and their appropriate treatment may be an effective way to prevent obesity in a subset of children with MC4R mutation.

Detection of auto-antibodies to DAT in the serum: interactions with DAT genotype and psycho-stimulant therapy for ADHD.

UNLABELLED: Interest is rising for auto-immune contribution in neuro-psychiatry. We evaluated the auto-antibodies against dopamine transporter (DAT aAbs) in 61 children (46 ADHD who met DSM-IV-TR criteria, 15 healthy controls). METHODS: ADHD patients were assigned, according to severity, either to a non-pharmacological therapy (NPT, N=32) or to a pharmacological treatment (PT, N=14) with methylphenidate (MPH). In ADHD children, blood samples were withdrawn twice, at recruitment (T0 basal) and after 6 weeks (T1); following 16 excluded subjects, DAT genotype was characterized (9-repeat or 10-repeat alleles; N=15 each). After 18 months of NPT or PT, some patients (carrying at least one 9-repeat allele) were blood sampled again (T2), for comparison with healthy controls (final n=8) RESULTS: Compared to NPT, basal DAT aAbs titers were higher within most severe patients (then assigned to PT), specifically if carrying a DAT 10/10 genotype. DAT aAbs levels of NPT group resulted highly correlated with distinct subscales of Conners' Parent/Teacher Scales (Rs>0.34), especially within DAT 10/10 genotype (Rs>0.53). While T1 titers were elevated over T0 baseline for NPT children, such an increase was not observed in PT patients carrying at least one 9-repeat allele, who also showed behavioral response to subchronic MPH. After 12-24 months of MPH exposure, DAT aAbs titers in PT subjects were comparable to those of healthy controls, while titers remained significantly elevated in NPT patients. Data warrant further research on serum DAT aAbs, which could be used to confirm ADHD diagnosis and/or to monitor therapeutic efficacy of MPH.

Reduction in retinal nerve fiber layer thickness in young adults with autism spectrum disorders.

Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism pathophysiology. All subjects underwent high-resolution spectral domain optical coherence tomography to evaluate RNFL thickness. HFA subjects presented with reduced global RNFL thickness compared both to AS subjects and controls. AS subjects showed a reduced nasal quadrant RNFL thickness compared to controls. Verbal-IQ/performance-IQ discrepancy correlated with RNFL thickness. Our data suggest that RNFL evaluation could help in the development of biological markers of autism pathophysiology.

Pharmacotherapy of autism spectrum disorders.

Although no pharmacological or behavioral therapy has currently proven effective for treating all core symptoms of autism, many dysfunctional behaviors may be treated pharmacologically. Drug treatments should always be part of a comprehensive management plan that includes behavioral and educational interventions, and should be focused on specific targets. Several classes of psychotropic medications have been used to decrease the wide range of "maladaptive" or "interfering" behaviors and associated medical problems that can interfere with relationships and physical health and hinder the implementation of various non-pharmacological interventions. Atypical neuroleptics have been shown to be useful in the treatment of behavioral symptoms in autism. Attention deficit and hyperactivity disorder medications may be effective for counteracting the additional features of hyperactivity and short attention span. Antiepileptic drugs and selective serotonin reuptake inhibitors have shown promising results, but there are no specific indications for them as of yet. With respect to potential drug targets, some clinical features are caused by a dysfunction in neurochemical signaling systems, and thus may improve with selective pharmacological interventions acting on specific abnormal neurobiological pathways. Recent animal studies can be useful models for understanding the common pathogenic pathways leading to autism spectrum disorders (ASDs), and have the potential to offer new biologically focused treatment options.

Attention-deficit hyperactivity disorder and binge eating disorder in a patient with 2q21.1-q22.2 deletion.

We report the case of a young male with attention-deficit hyperactivity disorder, oppositional defiant disorder, eating problems and overweight, and mild mental retardation. Karyotype analysis detected an apparently balanced translocation: t(1;2)(p34.1;q21.1) de novo. Array comparative genomic hybridization analysis defined a de-novo cryptic deletion of 2q21.1-q22.2 bands. The deletion, here first associated with this complex phenotype, encompasses several genes with a putative role in different domains of behavioral control and neurocognitive functions; their deregulated expression may influence metabolic pathways and the role of dopamine in reward, explaining the complex psychiatric phenotype and the pharmacotherapy response described in our patient.

Attention and executive functions profile in drug naive ADHD subtypes.

Attention deficit hyperactivity disorder (ADHD) has been associated with executive functioning and sustained and divided attention deficits. In order to clarify the questions on neurocognitive impairment in ADHD, we investigated the presence of specific executive functions (EFs) and attention deficit patterns in ADHD clinical subtypes. 50 patients with ADHD and 44 controls were evaluated. All subjects were boys and performed a clinical-psychopathological and neuropsychological battery. Five main domains of EFs and attention were studied. Executive functions-related neurocognitive abilities were used as control tasks. ADHD patients, inattentive and combined subtypes differ from controls on response inhibition, divided attention, phonological, and visual object working memory and on variability of reaction times measured with CPT. Comparison of ADHD subtypes, in five main domains of EFs, did not show evidence of different executive functioning profiles. Response inhibition can predict performance on working memory tests but it cannot predict performance on divided attention/set shifting and on sustained attention. ADHD boys exhibit a selective impairment on executive functions and attention tasks. These data suggest the involvement of partially independent neural circuits which control inhibition and divided attention in ADHD. Since right prefrontal cortex seems to be crucial in controlling response inhibition, while left dorsolateral prefrontal cortex seems important in modulating divided attention, these areas are deputated to be involved in the pathogenesis of neuropsychological deficits in ADHD subtypes. In addition, this study candidates the impairment in phonological and visual-object working memory as a possible neuropsychological trait in ADHD males with inattentive or combined subtypes.

Autism in tuberous sclerosis.

Despite considerable progress in the last few years, the neurobiologic basis of autism in tuberous sclerosis complex is still largely unknown and its clinical management represents a major challenge for child neurologists. Recent evidence suggests that early-onset refractory epilepsy and functional deficits associated with the anatomical lesions in the temporal lobes may be associated with autism. No one factor alone (cognitive impairment, tuber localization, occurrence of infantile spasms, focal EEG abnormalities), can be causally linked with the abnormal behaviour. Autism may also reflect a direct effect of the abnormal genetic program. Incidence of autism associated with Tuberous Sclerosis may be significantly higher than the rates of cardiac and renal abnormalities, for which screening is routinely conducted in this population. Hopefully, early diagnosis of autism will allow for earlier treatment and the potential for better outcome for children with Tuberous Sclerosis.