Diverse patterns of vulnerability to visual illusions in children with neurodevelopmental disorders.

Research on how children with neurodevelopmental disorders perceive, process, and interpret visual illusions (VIs) has been extensively focused on children with autism spectrum disorder providing controversial findings. In this study, we investigated the patterns of vulnerability to a wide set of VIs comprising 23 standard text book VIs and their variations in a clinical sample of children with neurodevelopmental disorders compared to typically developing children (TD). A total of 176 children, aged between 4.6 and 13.8 years old, were distributed into four groups: high-functioning autism (HFA; N = 23), attention-deficit/hyperactivity disorder (ADHD; N = 42), specific learning disorder (SLD; N = 70), and TD (N = 41). Regression models, adjusted for sex, age, and non-verbal IQ, showed that HFA was associated with greater responses accuracy than TD children to the full battery of VIs, to the cognitive illusions, to the distortions, and to both geometrical illusions of size/shape (cognitive distortions) and lightness contrast effects (physical distortions). The susceptibility of ADHD children was found attenuated for illusory contours and greater for paradoxical illusions in comparison with TD children. No significant differences were shown between the SLD group and the TD children. Our findings, which were adjusted for the same duration of visual working memory across groups, showed that there is a potential specific tendency of HFA children to failure of processing visual information in context. Contrarily, children with ADHD showed in general normal global processing such as children diagnosed with SLD.

Early Life Stress, Hormones, and Neurodevelopmental Disorders.

BACKGROUND: Early life stress (ELS) describes a broad spectrum of adverse and stressful prenatal events, namely, prenatal maternal stress (PMS), or early postnatal events, which can have detrimental long-term influences on the physiology, cognition, and behavior of an individual. There is abundant evidence indicating that ELS exerts its lasting effects on the physical and mental health of the individual, likely acting through a number of mediating mechanisms, including the disruption of developmental programming of the fetus. Neurodevelopmental disorders (NDDs), for example, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are a group of conditions that typically manifest during infancy, childhood, or adolescence and are characterized by developmental deficits in various domains. SUMMARY: The scope of the current mini-review is to provide an up-to-date summary of the findings regarding the association of ELS and NDDs and the possible hormonal mechanisms through which PMS exerts its impact on neurodevelopment. We focus on the available evidence regarding children and adolescents diagnosed with ADHD or ASD. ELS exposure during developmental vulnerability windows may increase the risk for either subclinical neuropsychological alterations or clinical conditions, such as NDDs. In fact, a large body of evidence underlies the association of ELS exposure and increased risk for NDDs in the offspring. KEY MESSAGES: The majority of data suggest that ELS, including PMS, may be associated with ADHD and ASD in the offspring, although there is no consensus regarding the critical developmental periods. Carefully controlled prospective studies are needed to determine the possible causal processes and mechanisms underlying the association of ELS and NDDs.

Psychometric Validation of the Greek Version of the Scale "Temper Loss" of the Questionnaire "Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB)".

It has become increasingly evident that vulnerability to psychopathology is identifiable early in life. A body of evidence suggests that the recognition and prevention of a spectrum of typical/atypical behaviors in preschoolers can lead to earlier diagnosis and treatment. The Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB) is a parent-completed instrument that has been developed recently to differentiate normative misbehaviors in early childhood from markers of clinical risk. The aim of the present study was to validate the "Temper Loss" Subscale in the Greek language and to assess its psychometric properties in healthy children. An on-print parent-report survey was conducted among Greek children, aged between 3 and 5.5 years. The survey included the MAP-DB and the Child Behavior Checklist (CBCL). A total of 400 respondents participated in the study. The analysis suggested that the Greek version of the MAP-DB's "Temper Loss" scale has good psychometric properties. The results of the Exploratory Factor Analysis (EFA) of the 22 items were able to explain 64.4% of the total variance. Internal consistency for the one subscale was satisfactory, with Cronbach's alpha at 0.970. This scale can be used by researchers and practitioners for the evaluation of dimensional phenotypes in early childhood.

Evaluating the Modulation of the Acoustic Startle Reflex in Children and Adolescents via Vertical EOG and EEG: Sex, Age, and Behavioral Effects.

Acoustic startle reflex (ASR) constitutes a reliable, cross-species indicator of sensorimotor and inhibitory mechanisms, showing distinct signature in cognitive aging, sex, and psychopathological characterization. ASR can be modulated by the prepulse inhibition (PPI) paradigm, which comprises the suppression of reactivity to a startling stimulus (pulse) following a weak prepulse (30- to 500-ms time difference), being widely linked to inhibitory capabilities of the sensorimotor system. If the prepulse-pulse tones are more clearly separated (500-2,000 ms), ASR amplitude is enhanced, termed as prepulse facilitation (PPF), reflecting sustained or selective attention. Our study aimed to investigate early-life sensorimotor sex/age differences using Electroencephalographic recordings to measure muscular and neural ASR in a healthy young population. Sixty-three children and adolescents aged 6.2-16.7 years (31 females) took part in the experiment. Neural ASR was assessed by two different analyses, namely, event-related potentials (ERPs) and first-derivative potentials (FDPs). As expected, PPF showed enhanced responses compared with PPI, as indicated by eyeblink, ERP and FDP measures, confirming the gating effect hypothesis. Sex-related differences were reflected in FDPs, with females showing higher ASR than males, suggesting increased levels of poststartle excitability. Intragroup age effects were evaluated via multipredictor regression models, noticing positive correlation between age versus eyeblink and ERP responses. Attention-related ERPs (N100 and P200) showed distinct patterns in PPI versus PPF, potentially indicative for alternative attentional allocation and block-out of sensory overload. Screening measures of participants' neurodevelopmental (assessed by Wechsler Intelligence Scale for Children) and behavioral (assessed by Child Behavior Checklist) markers were also associated with increased N100/P200 responses, presumably indexing synergy between perceptual consistency, personality profiling, and inhibitory performance. Conclusively, modulation of ASR by PPI and PPF is associated with biological sex and internal/external personality traits in childhood and adolescence, potentially useful to guide symptomatology and prevention of psychopathology.

Circadian cortisol profiles and hair cortisol concentration in patients with psoriasis: associations with anxiety, depressive symptomatology and disease severity

Background: There is evidence that stress and psoriasis interact bidirectionally. Specifically, stress is not only induced by psoriasis, but it is also considered a precipitating factor for onset or exacerbation of the disease. Neuroendocrine alterations of the stress system have been implicated in this association. Objectives: To assess the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis and hair cortisol levels in patients with psoriasis compared to healthy controls, and further explore whether suggested alterations in HPA axis activity are related to anthropometric, psychological, and disease activity/severity indices. Materials & Methods: We assessed stress levels quantified by questionnaires, psoriasis severity, and stress system activity based on HPA axis biomarkers. The sample comprised 18 adult patients with exacerbation of non-pustular psoriasis compared to 18 healthy controls (18-65 years old). In particular, salivary cortisol diurnal profiles and hair cortisol concentration were evaluated in both groups. Five distinct salivary samples were collected during a day of rest and 3-cm hair segments were cut. Results: A higher prevalence of self-reported anxiety, stress, and depressive symptoms was reported among psoriatic patients compared to healthy controls. Also, blunted salivary cortisol diurnal rhythm in psoriatic patients and a positive correlation of salivary cortisol concentration with state anxiety and psoriasis severity were revealed. No associations were shown between hair cortisol concentrations and disease presence/severity. Conclusion: We provide preliminary evidence that psoriasis patients may demonstrate a hypofunctional HPA axis, while our findings also suggest a complex interaction between HPA axis activity, psychosocial status and pathophysiological processes in psoriasis.

Stress System Activation in Children and Adolescents With Autism Spectrum Disorder.

The mission of the human stress system is the maintenance of homeostasis in the presence of real or perceived, acute or chronic stressors. The hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are the stress system-related neuroendocrine pathways. There is abundant evidence that children and adolescents with autism spectrum disorder (ASD) may exhibit atypical function within the HPA axis and the ANS both at the resting state and during the presence of social and/or non-social stressors. The aim of this review is to provide an up-to-date summary of the findings regarding stress system alterations in children and adolescents with ASD. We focus on the variations of stress hormones circadian rhythms, specifically cortisol and alpha-amylase (i.e., a surrogate index of epinephrine/norepinephrine secretion), and on the alterations of stress system responsivity to different stressors. Also, we present imaging and immunological findings that have been associated with stress system dysregulation in children and adolescents with ASD. Finally, we review the pivotal role of HPA axis-ANS coordination, the developmental trajectory of the stress system in ASD, and the possible role of early life stress in the dysregulation of the stress system demonstrated in children and adolescents with ASD. This synthesis will hopefully provide researchers with a foundation for an integrated approach to future research into stress system variations in children and adolescents with ASD.

Increased Serum Concentrations of High Mobility Group Box 1 (HMGB1) Protein in Children with Autism Spectrum Disorder.

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, p = 0.039). The Spearman's rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, p = 0.045) and with the SQ total score (rs = 0.42, p = 0.04) in the ASD group. These results show that HMGB1 serum concentrations are altered in ASD children, and suggest that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features observed in ASD.

Salivary cortisol and alpha-amylase daily profiles and stress responses to an academic performance test and a moral cognition task in children with neurodevelopmental disorders.

There is evidence that children with neurodevelopmental disorders may exhibit atypical responses to stress and alterations in concentrations and diurnal secretion of stress hormones. We assessed diurnal profiles and stress responses of salivary cortisol and alpha-amylase (sAA) in children with attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and specific learning disorder (SLD) compared to typically developing children (TD). A total of 157 children of both sexes, aged between 6 and 12 years old, took part in the study distributed into four groups: ADHD (N = 34), ASD (N = 56), SLD (N = 43) and TD (N = 24). Salivary samples were collected at three time points during a day, as well as before and 5 min after an academic performance test and a moral cognition task. ADHD children had lower evening and diurnal sAA levels, adjusted for age. Also, ASD children showed lower diurnal sAA secretion, adjusted for age. The mean percentage change for salivary cortisol and sAA after both tests did not differ between the groups. In conclusion, we demonstrated alterations in diurnal autonomic functioning in children with ADHD and ASD, while hypothalamic-pituitary-adrenal axis functioning did not differ between the clinical and the comparison groups.

Early Life Stress and Pediatric Posttraumatic Stress Disorder.

Traumatic stress exposure during critical periods of development may have essential and long-lasting effects on the physical and mental health of individuals. Two thirds of youth are exposed to potentially traumatic experiences by the age of 17, and approximately 5% of adolescents meet lifetime criteria for posttraumatic stress disorder (PTSD). The role of the stress system is the maintenance of homeostasis in the presence of real/perceived and acute/chronic stressors. Early-life stress (ELS) has an impact on neuronal brain networks involved in stress reactions, and could exert a programming effect on glucocorticoid signaling. Studies on pediatric PTSD reveal diverse neuroendocrine responses to adverse events and related long-term neuroendocrine and epigenetic alterations. Neuroendocrine, neuroimaging, and genetic studies in children with PTSD and ELS experiences are crucial in understanding risk and resilience factors, and also the natural history of PTSD.

Gender-dependent variations in optical illusions: evidence from N400 waveforms.

OBJECTIVE: The cognitive mechanisms (especially the gender-related ones) underlying optical illusion processing remain elusive. Since the N400 component of event-related potentials (ERPs) is an index of the semantic integration of information processing tasks, the present study focuses on gender-related differences in N400 waveforms elicited during the reasoning process applied to reach a valid conclusion of optical illusions engaging working memory (WM). APPROACH: Fifty-one healthy participants (28 males, age = 34.25 years ± 10.25, years of education = 16.00 years ± 1.78; and 23 females, age = 33.43 ± 7.93, years of education = 15.56 ± 1.82) were measured. The N400 ERP component was evoked by 39 optical illusions adjusted to induce WM. We compared brain activation patterns while participants maintained conclusions of the optical illusions in WM. The N400 of ERPs was recorded during the WM phase, during which participants were required to draw a logical conclusion regarding the correctness of the optical illusions. MAIN RESULTS: Analysis revealed that females compared to males exhibited significantly increased N400 amplitudes located at parietal and occipital sites, whereas males exhibited significantly higher N400 amplitudes located at frontal areas. Furthermore, females compared to males demonstrated significantly prolonged latencies of the N400 component located at right frontotemporal abductions. SIGNIFICANCE: These results suggest that coupling of optical illusions with WM engages distinct gender-related variations of brain semantic processing as reflected by the N400 ERP component. Based on the dual process account, our study gives support to the notion that women tend to employ a more deliberate and slower semantic reasoning than the men who tend to employ an automatic and fast one. Topographically, within the network sub-serving the semantic operation, the posterior brain areas responsible for sensorimotor integration-related processes elicit a greater brain activation among females while the anterior brain areas responsible for control and storage/retrieval operation elicit a greater brain activation among males.

Validation of the Patient Empowerment Strategies Questionnaire (PES-Q) in Greek adult patients with chronic insomnia: a pilot study on basic psychometric values.

AIM: The objectives of this study were to validate the Patient Empowerment Strategies Questionnaire (PES-Q) in a Greek sample and to study its psychometric properties in a sample of patients diagnosed with chronic insomnia. BACKGROUND: This is a validation of the PES-Q in Attikon General Hospital, School of Medicine, National and Kapodistrian University of Athens. The questionnaire was administered to 93 subjects aged between 18 and 85 years (mean age ± SD: 54.7 ± 15.2, 28% males). METHODS: The criterion validity of the questionnaire was tested with the use of four specific criteria: the Athens Insomnia Scale, the Pittsburg questionnaire (Pittsburg Sleep Quality Index), the Depression, Anxiety and Stress Scale, and the Self-Esteem Scale. FINDINGS: According to factor analysis results, the structure of the original scale was confirmed by the presence of one main factor in the Greek sample, explaining 40.1% of the variance of PES-Q queries. The questionnaire showed satisfactory reliability (Cronbach's α = 0.887). The results of the current study suggest that the PES-Q may be used as an accurate psychometric instrument for the purposes of chronic insomnia. Future research should examine the psychometric qualities of the PES-Q Greek version in a larger sample.

Serum concentrations and detection rates of selected organochlorine pesticides in a sample of Greek school-aged children with neurodevelopmental disorders.

Prospective studies indicate that the exposure to organochlorine pesticides (OCPs) during fetal life, infancy, and early childhood may be associated with features of neurodevelopmental disorders in children. However, few studies have investigated the concentrations of serum OCPs in children with categorically diagnosed neurodevelopmental disorders. The aim of this study was to assess the concentrations and detection rates of dichlorodiphenyltrichloroethane (DDT) metabolites, hexachlorocyclohexane (HCH) isomers, cyclodienes, and methoxychlor in serum samples of children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and specific learning disorder (SLD), all of normal intelligence, compared to typically developing controls (TD). In total, 114 schoolchildren, aged 6-13 years old, were assessed and distributed into four groups: ASD (n = 39), ADHD (n = 21), SLD (n = 32), and TD (n = 18). Each clinical group was compared to the TD group. Concentrations of serum OCPs were determined by gas chromatography and are presented as ng/g lipid. Concentrations of ß-HCH, the sum of HCH isomers, and o,p'-DDD were significantly higher in ASD children: ASD vs. TD (mean ± SD): 10.5 ± 7.7 vs. 6.1 ± 4.0, (p = 0.049); 12.0 ± 10.3 vs. 6.6 ± 4.0, (p = 0.025); 7.4 ± 6.5 vs. 2.8 ± 2.3, (p = 0.0019), respectively. The detection rates of p,p'-DDT, at least one substance from DDTs detected, and the cyclodiene heptachlor epoxide, were significantly lower in the ASD group: ASD vs. TD: 12.8% vs. 38.9%, (p = 0.037); 69.2% vs. 94.4%, (p = 0.044); 10.3% vs. 38.9%, (p = 0.026), respectively. No significant differences between the ADHD or SLD groups and the TD group were observed. We demonstrated higher serum concentrations and lower detection rates of selected OCPs in ASD than TD children. Our results add to potential neurodevelopmental concerns surrounding OCPs and provide evidence of specificity in the relations between HCHs and ASD.

Quetiapine and clarithromycin-induced neuroleptic malignant syndrome.

We report a case of neuroleptic malignant syndrome possibly caused by the combined administration of quetiapine and clarithromycin in a 75-year-old male patient. He was receiving quetiapine regularly. Two days before his admission to the hospital, he had been feverish and started receiving clarithromycin without consulting a doctor. Clarithromycin administration was interrupted 3 days after his admission because it was ineffective and because his clinical state was deteriorating. The patient presented altered level of consciousness and excessive muscular rigidity on his limbs, while he remained feverish (38.7 °C). Laboratory abnormalities included elevated serum creatine phosphokinase level (5.387 U/L), leukocytosis, and low serum iron. The patient was diagnosed with neuroleptic malignant syndrome, and quetiapine was immediately discontinued. After the following days, his muscle rigidity and mental status ameliorated, his fever withdrew, and his laboratory findings improved. The various features of the case are discussed in view of the fact that the concomitant administration of cytochrome 3A4 inhibitors, such as clarithromycin, is suggested to cause an increase of plasma concentrations of quetiapine. Thus, physicians should have a high index of suspicion of the interactions of commonly administered medications.