Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case-control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems.

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.

Perinatal complications, lipid peroxidation, and mental health problems in a large community pediatric sample.

Replicated evidence indicates that perinatal complications are associated with increased markers of oxidative stress and with mental health problems in children. However, there are fewer reports on the impact of perinatal complications in later phases of development. We aimed to investigate the estimated effects of perinatal complications on levels of lipid peroxidation and on psychopathology in children and adolescents. The study is part of the High Risk Cohort Study for Psychiatric Disorders; the population was composed by 554 students, 6-14 years of age. Serum levels of malondialdehyde, a product of lipid peroxidation, were measured by the TBARS method. A household interview with parents and caregivers was conducted and included inquiries about perinatal history, the Child Behavior Checklist (CBCL), and parent's evaluation, using the Mini International Psychiatric Interview (MINI). We created a cumulative risk index, conceptualized as each individual's cumulative exposure to perinatal complications. Results indicate that perinatal complications were associated with higher levels of TBARS. After adjusting for age, gender, socio-economic status, CBCL total problems score, parental psychopathology, and childhood maltreatment, children exposed to 3 or more perinatal complications had an 26.9% (95% CI 9.9%, 46.6%) increase in TBARS levels, relative to the unexposed group. Exploratory mediation analysis indicated that TBARS levels partially mediated the association between perinatal complications and externalizing problems. In conclusion, an adverse intrauterine and/or early life environment, as proxied by the cumulative exposure to perinatal complications, was independently associated with higher levels of lipid peroxidation in children and adolescents.

Epilepsy and behavioral changes, type 1 diabetes mellitus and a high titer of glutamic acid decarboxylase antibodies.

Autoantibodies to the 65 kDa isoform of glutamate acid decarboxylase (GAD65Ab) are associated with a range of clinical disorders, including type 1 diabetes (T1D) and stiff-person syndrome (SPS). In this article we describe a young girl who was diagnosed with T1D at the end of her first year of life and developed drug-resistant epilepsy 18 months later, followed by behavioral disturbances. She was admitted to our center at the age of 5 yr, at which time high GAD65Ab titers were detected in the patient's serum and cerebrospinal fluid (CSF). The titer remained elevated during 19 months of follow-up. Furthermore, GAD65Ab in both serum and CSF showed epitope binding characteristics similar to those observed for GAD65Ab in SPS patients, and GAD65Ab in the serum reduced GAD65 enzyme activity. Our results suggest an association between high GAD65Ab titers and epilepsy in children with T1D. Careful titration and characterization of GAD65Ab regarding inhibition of enzyme activity and epitope specificity may be helpful in identifying T1D patients at risk for neurological complications.

Preterm born 9-year-olds have elevated IGF-1 and low prolactin, but levels vary with behavioural and eating disorders.

AIM: This study examined the relationship between hypothalamic-associated hormones and behavioural and eating disorders in children with low birthweight. METHODS: We included 100 children (mean age 9.7 years): 39 were born preterm at <32 gestational weeks, 28 were full-term, but small for gestational age, and 33 were full-term controls. Behavioural histories were analysed, together with fasting blood samples of leptin, insulin, insulin-like growth factor-1 (IGF-I), prolactin, glucagon and cortisol. RESULTS: Preterm children had lower prolactin (p = 0.01) and higher IGF-I than controls (p < 0.05, adjusted for confounders), despite being significantly shorter than the predicted target height (p < 0.001). More preterm children displayed behavioural disorders (38% versus 10%, p < 0.001) and eating disorders (26% versus 8%, p < 0.05) than full-term children. These disorders were associated with lower leptin (p < 0.01), insulin (p < 0.05) and IGF-I (p < 0.05), but correlations between these hormones and leptin were similar among the groups. Combined behavioural and eating disorders were only observed in preterm children, who were also the shortest in height. CONCLUSION: Behavioural and eating disorders among preterm children were associated with low leptin, insulin and IGF-1. Low prolactin in all preterm children indicated an increased dopaminergic tonus, which might inhibit body weight incrementation. This raises speculation about IGF-I receptor insensitivity.

Increased anti-phospholipid antibodies in autism spectrum disorders.

Autism spectrum disorders (ASD) are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD) controls and children with developmental delays (DD) other than ASD. We found that levels of anti-cardiolipin, ß 2-glycoprotein 1, and anti-phosphoserine antibodies were elevated in children with ASD compared with age-matched TD and DD controls. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD.

Cortisol predicts behavioral dysregulation and length of stay among children admitted for psychiatric inpatient treatment.

Individual differences in behavioral regulation system (BRS) and stress response system (SRS) functioning may reflect greater biological sensitivity to context. The current study tested whether children's cortisol, a measure of the SRS, was related to observed dysregulated behavior, an indicator of the BRS, in a sample of children admitted for acute psychiatric inpatient care. In addition, cortisol and dysregulated behavior were tested as unique predictors of length of hospitalization over and above demographic factors, prior treatment history, and caretaker-reported psychiatric symptoms. The latter variables were tested as potential moderators of the relations of BRS and SRS functioning to length of hospitalization. Plasma cortisol was collected on the morning following hospital admission for 544 children (ages 6-12; 73% boys; 61% ethnic minority). Dysregulated behavior was operationalized as the mean number of timeouts administered by staff for noncompliant behavior per day of hospitalization. Caretakers reported on youth internalizing and externalizing symptomatology. Higher cortisol was modestly associated with greater dysregulated behavior. In a model including both cortisol and dysregulated behavior, each predicted longer hospitalization. Cortisol was positively related to length of stay only for children previously hospitalized, and the relation of dysregulated behavior to length of stay was stronger for older children. Dysregulated behavior and cortisol are related but independent predictors of acute psychiatric hospitalization duration. Direct measures of the SRS can add to the clinical picture regarding hospitalization in ways that observed behavior and caretaker report alone cannot.

Iron, Lead, and Children's Behavior and Cognition.

Iron deficiency (ID) is the most common micronutrient deficiency in the world, with consequences of ID and ID anemia (IDA) in young children including behavioral and cognitive deficits. In turn, lead exposure is one of the most common environmental toxicants affecting children. Elevated blood lead levels (BLLs) in young children are also associated with behavioral and cognitive deficits. The metabolic and physiological connections between iron and lead, including a common route of entry into the body and similar neural targets, suggest a considerable overlap in their effects on functional outcomes. Very few studies have examined the existence of increased susceptibility to lead neurotoxicity in children with ID, but there is evidence that ID and BLL are independently associated with cognition and behavior. Children's susceptibility to both ID and elevated BLLs will likely depend on the timing and severity of both exposures, something that should be investigated systematically.

Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome.

Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. A potential role for immune dysfunction has been suggested in ASD. To test this hypothesis, we investigated evidence of differential cytokine release in plasma samples obtained from 2 to 5 year-old children with ASD compared with age-matched typically developing (TD) children and children with developmental disabilities other than autism (DD). Participants were recruited as part of the population based case-control CHARGE (Childhood Autism Risks from Genetics and Environment) study and included: 97 participants with a confirmed diagnosis of ASD using standard assessments (DSM IV criteria and ADOS, ADI-R), 87 confirmed TD controls, and 39 confirmed DD controls. Plasma was isolated and cytokine production was assessed by multiplex Luminex™ analysis. Observations indicate significant increases in plasma levels of a number of cytokines, including IL-1ß, IL-6, IL-8 and IL-12p40 in the ASD group compared with TD controls (p<0.04). Moreover, when the ASD group was separated based on the onset of symptoms, it was noted that the increased cytokine levels were predominantly in children who had a regressive form of ASD. In addition, increasing cytokine levels were associated with more impaired communication and aberrant behaviors. In conclusion, using larger number of participants than previous studies, we report significantly shifted cytokine profiles in ASD. These findings suggest that ongoing inflammatory responses may be linked to disturbances in behavior and require confirmation in larger replication studies. The characterization of immunological parameters in ASD has important implications for diagnosis, and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of ASD.

Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders.

Autism spectrum disorders (ASDs) are characterized by impaired language and social skills, often with restricted interests and stereotyped behaviors. A previous investigation of blood plasma from children with ASDs (mean age=5½ years) demonstrated that 21% of samples contained autoantibodies that reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al., 2009). In order to characterize the clinical features of children positive for these autoantibodies, we analyzed plasma samples from children enrolled in the Autism Phenome Project, a multidisciplinary project aimed at identifying subtypes of ASD. Plasma from male and female children (mean age=3.2 years) was analyzed immunohistochemically for the presence of autoantibodies using histological sections of macaque monkey brain. Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers. Staining of neurons, punctate profiles in the molecular layer of the dentate gyrus, and neuronal nuclei were also observed. Taken together, 42% of controls and subjects with ASD demonstrated immunoreactivity to some neural element. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems. Children whose plasma was immunoreactive with neuronal cell bodies scored higher on multiple CBCL scales. These studies indicate that additional research into the genesis and prevalence of brain-directed autoantibodies is warranted.

The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior.

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.

Negative association between plasma cortisol levels and aggression in a high-risk community sample of adolescents.

In this study, the association of aggressive behavior and personality traits with plasma cortisol levels was investigated in a high-risk community sample of adolescents. Plasma cortisol levels were collected in 245 fifteen-year-olds (118 males, 127 females) from an epidemiological cohort study of children at risk for psychopathology. Additionally, measures of reactive and proactive aggression, externalizing behavior and callous-unemotional together with impulsive personality features were assessed. Both subtypes of aggression as well as delinquent behavior and impulsive personality traits showed significant negative correlations with plasma cortisol levels. This association was observed in males, but not in females. In both gender groups, callous-unemotional traits were unrelated to plasma cortisol levels. This result suggests that the association between cortisol levels and aggression in adolescents is mediated rather by impulsivity than by unemotional or psychopathic traits.

Serum concentrations, therapeutic response and side effects in children and adolescents with impulsive-aggressive symptoms during risperidone therapy.

INTRODUCTION: The aim of this prospective naturalistic study was to examine for the first time the relationship between dosage, serum concentration and clinical outcome in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. METHODS: Steady state trough serum concentrations of risperidone and 9-hydroxyrisperidone (the active moiety) were measured in 103 subjects. The therapeutic effect was assessed by the clinical global impression improvement subscale and side effects by the Udvalg for Kliniske Undersogelser-side effect rating scale. RESULTS: We found a linear relationship between the risperidone dose and the serum concentration of the active moiety (Spearman rho=0.53) and no correlation between the serum concentration and either the therapeutic effect or side effects. There was no effect of gender and co-medication. DISCUSSION: This study has the typical limitations of naturalistic studies, therefore our results should be interpreted with caution. Based on the serum concentrations at the therapeutically effective dose range (0.25-1.5 mg/day) we obtained first information on a possibly appropriate therapeutic serum range for the risperidone treatment of children and adolescents with impulsive-aggressive symptoms. Further studies with greater sample sizes are needed to validate our results and to examine the influence of genetic polymorphisms on the serum concentration of risperidone.

Trajectories of internalising and externalising symptoms and inflammation in the general child population.

BACKGROUND: Elevations in inflammatory marker levels have been shown to precede internalising and externalising problems in the general child population. One study has found the reverse, that elevations in inflammatory marker levels in childhood follow internalising and externalising problems. However, the authors did not explore the role of the course of these problems in childhood or adjust for a number of potential confounders including psychosocial stressors and prenatal and perinatal exposures. AIMS: To investigate the association in childhood between the growth of internalising and externalising symptoms and levels of inflammatory markers, while accounting for potential confounders. METHODS: Using data from the Avon Longitudinal Study of Parents and Children, we tested the association between the trajectories of internalising (emotional and social) and externalising (hyperactivity and conduct) problems, at ages 4, 6, 8 and 9 years, and levels of C-reactive protein (CRP) and interleukin 6 (IL-6) at age 9 years. We analysed data (n = 4525) using latent growth curve modelling and linear regression. RESULTS: Children who had increasing levels of internalising symptoms over childhood were more likely to have higher levels of CRP and IL-6 at 9 years of age, even after adjustment for confounders. A one-unit increase in the rate of annual change of internalising symptoms was related to an increase of 12% and 8% in the level of CRP and IL-6, respectively. However, there was no evidence for an association between externalising symptoms and either inflammatory marker. CONCLUSIONS: This study is the first step towards identifying a robust pathway, via increases in emotional and social difficulties, to elevated inflammation in healthy children. This association, if causal, suggests that effective interventions for children experiencing chronic emotional and social difficulties could also have physical health benefits.

Association between prolonged separation from parents and allostatic load among children in China.

OBJECTIVE: To capture the association of exposure to prolonged separation from both parents early in life and allostatic load (AL), a measure of biological multi-system dysregulation. METHODS: We used data from 557 7-12-year-old children enrolled in rural area of Chizhou city, Anhui Province, China. We computed an AL score based on eleven biomarkers representing four regulatory systems: immune/inflammatory system (high sensitivity C-reactive protein); metabolic system (body mass index; high density lipoprotein; low density lipoprotein, total cholesterol; triglycerides; fasting glucose; glycated hemoglobin; insulin) and cardiovascular system (systolic and diastolic blood pressure). Child's experiences of parent-child separation were collected a brief online questionnaire by parents of children. RESULTS: More than 1 in 3 of our participants separated with both parents at age 6 or younger and nearly 1 in 10 persistently separated from both parents after birth. The AL score was significantly higher among children separated from both parents during early childhood (3.25 ± 1.98) or persistently since birth (3.48 ± 1.92), compared with those who did not separated from both parents (2.34 ± 1.53, F = 12.992, P<0.001). After adjustment of demographic covariates, body mass index as well as parent frequency of communication and parental warmth, children who separated from both parents in early childhood (ß = 0.84, 95%CI:0.40, 1.28, P < 0.001) or persistently into adolescence (ß = 1.27, 95%CI:0.43, 2.12, P = 0.003) evinced the highest levels of AL. CONCLUSION: This study is the first to show an association between prolonged parent-child separation and physiological wear-and-tear as measured by AL, which provides potential insights into the biological mechanisms underpinning long-term health outcomes in contexts of parent-child separation.

Ghrelin and leptin levels in children with anxiety disorders.

Background Anxiety disorders are common psychiatric disorders in childhood and an important health problem that is associated with the risk of serious mental, educational and economical problems. Researchers have mentioned many different mechanisms in the etiopathology of anxiety disorders. This study aimed to investigate ghrelin and leptin levels in children with anxiety disorders and thus to contribute to the clarification of anxiety in children. Methods Forty-three children aged 6-12 years with a diagnosis of the Anxiety Disorder according to DSM 5 and 21 healthy children age- and gender-matched to the study group were included. All the subjects were assessed with Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and State-Trait Anxiety Inventory for Children (STAI-C) scale. Blood samples were obtained in the morning and serum ghrelin and leptin levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. Results In the anxiety group the ghrelin levels were higher than the control group (p = 0.037) but there was no significant difference between the leptin levels (p = 0.430). Also, when the girls in the anxiety group and the girls in the control group were compared, ghrelin levels were higher in the anxiety group (p < 0.01). Conclusions These findings suggest that ghrelin may play a significant role in the etiologic mechanisms of anxiety disorders. However, more detailed studies are needed to explain the linkage between anxiety disorders and neuropeptides.

Elevated Gestational IL-13 During Fetal Development Is Associated With Hyperactivity and Inattention in Eight-Year-Old Children.

Maternal immune activation (MIA) during fetal development leads to behavioral and psychological disorders in the offspring. Concomitantly, insufficient supply of polyunsaturated fatty acids (PUFAs) is suspected to contribute to early neuronal maldevelopment due to the immune modulatory capabilities of PUFAs. However, human data are missing considering both of these aspects and their impact on children's behavioral outcomes. In line, this study aimed to elucidate the influence of gestational cytokines and PUFA-containing lipids during late pregnancy on behavioral sequelae in childhood, particularly focusing on an immune activation shaped by a history of maternal atopic diseases instead of a pathogen-mediated immune response. Based on the prospective mother-child cohort LINA we assessed the unstimulated blood cytokine profiles and concentrations of PUFA-containing lipids of 293 mothers at the 34th week of pregnancy. Maternal history of atopic diseases was obtained from questionnaires and behavior in eight-year-old children was assessed by the standardized Strength and Difficulties Questionnaires (SDQ) generating scores for hyperactivity/inattention, emotional symptoms, conduct problems, and peer relationship problems. Elevated IL-13 increased the risk for the child to show behavioral difficulties, in particular, hyperactive/inattentive behavior [adj. OR (95% CI): 2.47 (1.51-4.02), n = 255 vs. 38] at the age of eight years. Although the presence of maternal atopic dermatitis (AD) was associated with increased gestational IL-13 concentrations [adj. MR (95% CI): 1.17 (1.04-1.32)], no effect on children's behavioral difficulties was observed. However, a decrease in the PUFA containing lipid species PC aa C38:6 was not only associated with an increased gestational IL-13 concentration but also mediated the indirect effect of low PC aa C38:6 concentrations on children's abnormal behavior independent of maternal AD. We additionally assessed whether maternal IL-13 and PC aa C38:6 concentrations translate their effect by altering children's cord blood PC aa C38:6 and IL-13. While also the children's cord blood IL-13 was related to children's behavior, no effect of children's PC aa C38:6 was observed. This is the first study demonstrating that elevated gestational IL-13 increases the risk for children to develop behavioral difficulties. Analyses suggest that a reduced supply of gestational PC aa C38:6 contributes to elevated gestational IL-13 leading to behavioral sequelae in the offspring.

Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes.

Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. There is evidence of both immune dysregulation and autoimmune phenomena in autism. We examined the regulatory cytokine transforming growth factor beta-1 (TGF beta 1) because of its role in controlling immune responses. Plasma levels of active TGF beta 1 were evaluated in 75 children with ASD compared with 68 controls. Children with ASD had significantly lower plasma TGF beta 1 levels compared with typically developing controls (p=0.0017) and compared with children with developmental disabilities other than ASD (p=0.0037), after adjusting for age and gender. In addition, there were significant correlations between psychological measures and TGF beta 1 levels, such that lower TGF beta 1 levels were associated with lower adaptive behaviors and worse behavioral symptoms. The data suggest that immune responses in autism may be inappropriately regulated due to reductions in TGF beta 1. Such immune dysregulation may predispose to the development of possible autoimmune responses and/or adverse neuroimmune interactions during critical windows in development.

Early deprivation and home basal cortisol levels: a study of internationally adopted children.

Animal studies reveal that early deprivation impairs regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, potentially increasing vulnerability to stressors throughout life. To examine early deprivation effects on basal HPA axis activity in humans, basal cortisol levels were examined in 164 internationally adopted children who had experienced varying degrees of preadoption deprivation. Duration of institutional care, age at adoption, and parent ratings of preadoption neglect indexed a latent factor of Deprived Care. Adoption measures of height and weight standardized to World Health Organisation norms indexed a latent factor of Growth Delay that was viewed as another reflection of deprivation. Cortisol samples were collected 3.3-11.6 years postadoption (Md = 7.3 years) at home on 3 days approximately 30 min after wakeup and before bedtime. Both early a.m. levels and the decrease in cortisol across the day were examined. A structural equation model revealed that preadoption Deprived Care predicted Growth Delay at adoption and Growth Delay predicted higher morning cortisol levels and a larger diurnal cortisol decrease.

Cortisol and externalizing behavior in children and adolescents: mixed meta-analytic evidence for the inverse relation of basal cortisol and cortisol reactivity with externalizing behavior.

An inverse relation between cortisol (re)activity and externalizing behavior has been hypothesized, but research findings seem equivocal. We tested this hypo(re)activity hypothesis in two meta-analyses, one for basal cortisol (k = 72 studies, N = 5,480) and one for cortisol reactivity to a stressor (k = 29 studies, N = 2,601). No association was found between cortisol reactivity and externalizing behaviors (r = -.04, 95% CI = -.11, .02). However, the relation between basal cortisol and externalizing behavior was significant but small (r = -.05, 95% CI = -.10, -.002). The age of the children significantly moderated this relation: Externalizing behavior was associated with higher basal cortisol (hyperactivity) in preschoolers (r = .09, 95% CI = .002, .17), and with lower basal cortisol (hypoactivity) in elementary school-aged children (r = -.14, 95% CI = -.19, -.08). There was no significant relation between cortisol and externalizing behavior in adolescents.