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Background: Human scalp hair is a validated bio-substrate for monitoring various exposures in childhood including contextual stressors, environmental toxins, prescription or non-prescription drugs. Linear hair growth rates (HGR) are required to accurately interpret hair biomarker concentrations., Methods: We measured HGR in a prospective cohort of preschool children (N = 266) aged 9-72 months and assessed demographic factors, anthropometrics, and hair protein content (HPC). We examined HGR differences by age, sex, race, height, hair pigment, and season, and used univariable and multivariable linear regression models to identify HGR-related factors., Results: Infants below 1 year (288 ± 61 μm/day) had slower HGR than children aged 2-5 years (p = 0.0073). Dark-haired children (352 ± 52 μm/day) had higher HGR than light-haired children (325 ± 50 μm/day; p = 0.0019). Asian subjects had the highest HGR overall (p = 0.016). Younger children had higher HPC (p = 0.0014) and their HPC-adjusted HGRs were slower than older children (p = 0.0073). Age, height, hair pigmentation, and HPC were related to HGR in multivariable regression models., Conclusions: We identified age, height, hair pigment, and hair protein concentration as significant determinants of linear HGRs. These findings help explain the known hair biomarker differences between children and adults and aid accurate interpretation of hair biomarker results in preschool children., Impact: Discovery of hair biomarkers in the past few decades has transformed scientific disciplines like toxicology, pharmacology, epidemiology, forensics, healthcare, and developmental psychology. Identifying determinants of hair growth in children is essential for accurate interpretation of hair biomarker results in pediatric clinical studies. Childhood hair growth rates define the time-periods of biomarker incorporation into growing hair, essential for interpreting the biomarkers associated with environmental exposures and the mind-brain-body connectome. Our study describes age-, sex-, and height-based distributions of linear hair growth rates and provides determinants of linear hair growth rates in a large population of children. Age, height, hair pigmentation, and hair protein content are determinants of hair growth rates and should be accounted for in child hair biomarkers studies. Our findings on hair protein content and linear hair growth rates may provide physiological explanations for differences in hair growth rates and biomarkers in preschool children as compared to adults., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Early life stress has enduring effects on physical and mental health. Hair cortisol concentrations (HCCs) reflect exposures to contextual stressors in early life, but are understudied in preschool children., Methods: Hair samples from children (N = 693) during clinic visits (CVs) scheduled at 1-4 years (CV1-CV4) were measured using validated assay methods for HCC., Results: HCCs were highest at CV1 and decreased at CV2-CV4, with no sex differences. Black children had higher HCC than White/other children; these differences persisted even after adjusting for socioeconomic factors. Bivariable analyses showed significant effects on HCC for Black race, with specific demographic and psychosocial factors at different ages. Multivariable analyses showed that higher HCC at CV1 were associated with Black race and male sex; at CV2 with Black race, lower maternal self-esteem, socioeconomic adversity, and the child's risk for developmental delay; at CV3 with Black race; at CV4 with maternal depression and the child's prior HCC values., Conclusions: HCCs were higher in Black children than White/other races; differences were related to maternal factors, socioeconomic adversity, and the child's risk for developmental delay. Public health measures to reduce disparities between Blacks and other races must also consider the long-term effects of chronic stress in early life.

Little research has investigated the use of electrophysiological biomarkers in childhood and adolescence to distinguish early onset psychosis and the clinical high risk state. The P300 evoked potential is a robust neurophysiological marker of schizophrenia that is dampened in patients with schizophrenia and, less consistently, in those with affective psychoses and those at clinical high risk for psychosis (CHR). How it may differ between patients with psychotic disorders (PS) and CHR is less studied, especially in youth. The current study compared P300 activity among children and adolescents, aged 5-18 years, at CHR (n = 43), with PS (n = 28), and healthy controls (HC; n = 24). Participants engaged in an auditory event-related potential (ERP) task to elicit a P300 response and completed clinical interviews to verify symptoms and diagnoses. Linear regression analyses revealed a decrease in P300 amplitude with increased severity of psychotic symptoms. PS participants showed a diminished P300 response compared to those at CHR and HC, particularly among adolescents aged 13-18. This response was most evident at centroparietal and parietal locations in the right hemisphere. The findings suggest that high risk and psychotic symptomatology is linked to attenuated parietal P300 activity in youth as young as 13 years. Further exploration of the P300 as a biomarker for psychosis in very young patients could inform tailored, appropriate interventions at early stages of disease progression. Future research should evaluate whether specific phenotypic and genotypic characteristics are differentially associated with neurophysiological biomarkers and whether P300 attenuation in CHR youth can predict later symptom severity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: Previous research has demonstrated a strong association between early trauma exposure and the development of psychotic symptoms. However, few of these studies have included young adolescents and children. This study investigated rates and number of potentially traumatic experiences (PTEs) among typically developing youth (TD; n = 21), youth at clinical high risk for psychosis (CHR; n = 38), and youth with a psychotic disorder (PD; n = 28) between 7 and 18 years of age. CHR participants were further evaluated to determine whether a history of PTEs was associated with prodromal symptom severity., Methods: Study group inclusion was determined by structured interviews. Trauma history was assessed using the post-traumatic stress disorder module of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. CHR participants with vs without a history of PTEs were compared on severity of prodromal symptoms., Results: CHR and PD participants reported significantly higher rates and numbers of PTEs than TD participants. Contrary to expectations and prior research, CHR participants with vs without a history of PTEs did not differ in prodromal symptom severity. Explanations and implications for the findings are discussed., Conclusions: These findings suggest that the relationship between trauma and the development of psychotic symptoms extends to children and adolescents as young as 7 years of age. This study underscores the importance of screening for trauma exposure among youth seeking treatment for psychotic symptoms., (© 2018 John Wiley & Sons Australia, Ltd.)

Aim: Early life adversity leads to enduring effects on physical and mental health, school performance and other outcomes. We sought to identify potentially modifiable factors associated with socioeconomic adversity in early life., Methods: We enrolled 1503 pregnant women aged 16-40 years, without pregnancy complications or pre-existing conditions from Shelby County, Tennessee. Social, familial and economic variables were analysed using principal components (PCs) analyses to generate the Socioeconomic Adversity Index (SAI). This was replicated using the National Survey of Children's Health (NSCH). Health and social outcomes were compared across the quintile groups defined by SAI values at the county, state and national levels., Results: Significant differences occurred across the SAI Quintile-1 to Quintile-5 groups in marital status, household structure, annual income, education and health insurance. Significantly worse health and social outcomes occurred in the lower versus higher SAI quintiles, including maternal depression, parental incarceration, child's birthweight and potential for child abuse. Maternal age and race also differed significantly across the SAI quintiles., Conclusion: Modifiable factors contributing to socioeconomic adversity in early life included marital status, household structure, annual income, education and health insurance. Those exposed to greater socioeconomic adversity as defined by SAI values had significantly worse maternal and child outcomes., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Intro: One of the more debilitating functional outcomes of schizophrenia-spectrum disorders is social impairment. Previous studies have identified impaired social functioning both in the prodromal phase of psychosis and after acute symptoms abate, suggesting that social impairment represents a core deficit in psychosis not directly linked to psychotic episodes or symptom severity. To date, research in this area has focused primarily on adult populations rather than children, and has not directly assessed social language in individuals across the psychosis continuum., Methods: 81 youth ages 7-18 (N = 24 Typically Developing [TD], N = 36 Clinical High Risk [CHR], N = 21 Psychotic Disorder [PD]) were recruited. Youth participants were administered the Social Language Development Test (SLDT), and parent(s)/guardian(s) completed the Social Responsiveness Scale-II (SRS-II)., Results: Social language ability was not associated with social impairment. PD participants performed significantly worse on the SLDT than TD participants. CHR and PD participants were both rated as having experienced significantly greater social impairment than TD participants on every subscale of the SRS-II., Discussion: Deficits in social language ability and social functioning are strong candidates for phenotypic markers of psychosis, and may be evident earlier in development than previous work has demonstrated. Additionally, the severity of social impairment did not differ between CHR and PD participants, further supporting that social cognitive deficits and social impairment, while related to symptom severity, are discrete deficits in individuals with and at risk for psychosis. These results highlight the importance of addressing social skills for individuals presenting in clinical settings with psychotic symptoms, including children., (Copyright © 2018. Published by Elsevier B.V.)

Background: TRRAP encodes a multidomain protein kinase that works as a genetic cofactor to influence DNA methylation patterns, DNA damage repair, and chromatin remodeling. TRRAP protein is vital to early neural developmental processes, and variants in this gene have been associated with schizophrenia and childhood disintegrative disorder., Case Presentation: Here, we report on a patient with a de novo nonsynonymous TRRAP single-nucleotide variant (EST00000355540.3:c.5957G > A, p.Arg1986Gln) and early onset major depression accompanied by a psychotic episode (before age 10) that occurred in the context of longer standing nonverbal learning disability and a past history of obsessions and compulsions., Conclusions: The de novo variant and presentation of very early onset psychosis indicate a rare Mendelian disorder inheritance model. The genotype and behavioral abnormalities of this patient are reviewed.

Objective: Suicidal thoughts and behaviors (STBs) are prevalent among youth with psychotic disorders (PD) relative to the general population. Recent research now suggests that STBs may present during the prodromal phase of the disease, or the clinical high risk (CHR) state. While this knowledge is important for the development of suicide prevention strategies in adolescent and adult populations, it remains unclear whether risk for suicide extends to children with or at risk for psychosis. The current study is an extension of previous work assessing STBs in youth across the psychosis continuum. We examine STBs in 37 CHR and PD children ages 7-13 years old, and further explore the prodromal symptom correlates of STB severity among CHR children., Results: CHR and PD children endorsed STBs with a frequency and severity similar to what is observed in older CHR and PD populations. A number of children had never previously vocalized their suicidal plans or intent. Among CHR children, Social Anhedonia and Odd Behavior or Appearance were significantly correlated with STB severity. These findings underscore the importance of screening for STBs even in young children presenting with psychotic symptoms.

Background: Previous research has demonstrated elevated rates of suicide attempts and ideation in individuals with psychosis. This study investigated rates and severity of suicidal behavior in youth with and at clinical high risk for psychosis, and examined the positive, negative, and disorganized symptoms associated with suicidal behaviors among the clinical high risk group., Methods: Eighty-six youth ages 7-18 (n=21 non-clinical controls [NCC], n=40 clinical high risk [CHR], n=25 diagnosed psychotic disorder [PD]) were recruited. CHR and PD participants were identified using the Structured Interview for Prodromal Symptoms (SIPS) and Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL). All participants completed the Suicide Behaviors Questionnaire-Revised (SBQ-R)., Results: Findings indicated significantly higher levels of suicidal behavior among CHR and PD relative to NCC participants (F=7.64, p=0.001). 17.5% of CHR participants had previously attempted suicide. Dysphoric Mood and Odd Behavior or Appearance were significantly correlated with suicidal behavior severity among CHR youth., Conclusion: Suicidal behavior was observed with greater frequency and severity in the CHR and PD groups than in the NCC group. CHR suicidal behavior severity was correlated most strongly with Dysphoric Mood and Odd Behavior or Appearance, a relationship which warrants further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Suicide is the leading cause of premature death in individuals with psychotic disorders. Risk for onset of suicidal behaviors tends to begin in adolescence, remaining high into young adulthood. The present study aims to evaluate the interplay of early onset psychosis and suicide risk by examining suicidal behaviors (ideation, planning, and attempts) in children and adolescents with psychotic disorders (PD) compared to typically developing peers (TD). Twenty five youths were recruited and were diagnostically evaluated for psychosis. We found that the PD children exhibited significantly higher levels of suicidal behaviors than TD children, even when parsed into individual at-risk behaviors., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis., (© 2016 Wiley Periodicals, Inc.)

Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.

Background: The N100 is a negative deflection in the surface EEG approximately 100 ms after an auditory signal. It has been shown to be reduced in individuals with schizophrenia and those at clinical high risk (CHR). N100 blunting may index neural network dysfunction underlying psychotic symptoms. This phenomenon has received little attention in pediatric populations., Method: This cross-sectional study compared the N100 response measured via the average EEG response at the left medial frontal position FC1 to 150 sinusoidal tones in participants ages 5 to 17 years with a CHR syndrome (n=29), a psychotic disorder (n=22), or healthy controls (n=17)., Results: Linear regression analyses that considered potential covariates (age, gender, handedness, family mental health history, medication usage) revealed decreasing N100 amplitude with increasing severity of psychotic symptomatology from healthy to CHR to psychotic level., Conclusions: Longitudinal assessment of the N100 in CHR children who do and do not develop psychosis will inform whether it predicts transition to psychosis and if its response to treatment predicts symptom change., (Copyright © 2015 Elsevier B.V. All rights reserved.)