Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Deviations from a typical development of the cerebellum in youth are associated with psychopathology, executive functions and educational outcomes.

BACKGROUND: Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. METHODS: Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. RESULTS: Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. CONCLUSIONS: Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Replication of a predictive model for youth ADHD in an independent sample from a developing country.

BACKGROUND: Very few predictive models in Psychiatry had their performance validated in independent external samples. A previously developed multivariable demographic model for attention-deficit/hyperactivity disorder (ADHD) accurately predicted young adulthood ADHD using clinical and demographical information collected in childhood in three samples from developed countries, but failed to replicate its performance in a sample from a developing country. Furthermore, consolidated risk factors for ADHD were not included among its predictors. METHODS: Participants were 1905 children and adolescents from a community-based sample and followed from ages 6 to 14 years at baseline to ages 14 to 23 years (mean age 18) at follow-up. We applied the intercept and weights of the original model to the data, calculating the predicted probability of each participant according to the set of predictors collected in childhood, and compared the estimates with the actual outcome (ADHD) collected during adolescence and young adulthood. We explored the performance of the original model, and of models including novel predictors (prematurity, family history of ADHD, and polygenic risk score for ADHD). RESULTS: The observed area under the curve of the original model was .76 (95% Confidence Interval .70 to .82). The multivariable demographical model outperformed single variable models using only prematurity, family history, or the ADHD PRS. Adding either of these variables, or all at once, did not improve the performance of the original demographical model. CONCLUSIONS: Our findings suggest that the originally developed ADHD predictive model is suitable for use in different settings for clinical and research purposes.

Disentangling the influences of parental genetics on offspring's cognition, education, and psychopathology via genetic and phenotypic pathways.

BACKGROUND: Specific pathways of intergenerational transmission of behavioral traits remain unclear. Here, we aim to investigate how parental genetics influence offspring cognition, educational attainment, and psychopathology in youth. METHODS: Participants for the discovery sample were 2,189 offspring (aged 6-14 years), 1898 mothers and 1,017 fathers who underwent genotyping, psychiatric, and cognitive assessments. We calculated polygenic scores (PGS) for cognition, educational attainment, attention-deficit hyperactivity disorder (ADHD), and schizophrenia for the trios. Phenotypes studied included educational and cognitive measures, ADHD and psychotic symptoms. We used a stepwise approach and multiple mediation models to analyze the effect of parental PGS on offspring traits via offspring PGS and parental phenotype. Significant results were replicated in a sample of 1,029 adolescents, 363 mothers, and 307 fathers. RESULTS: Maternal and paternal PGS for cognition influenced offspring general intelligence and executive function via offspring PGS (genetic pathway) and parental education (phenotypic pathway). Similar results were found for parental PGS for educational attainment and offspring reading and writing skills. These pathways fully explained associations between parental PGS and offspring phenotypes, without residual direct association. Associations with maternal, but not paternal, PGS were replicated. No associations were found between parental PGS for psychopathology and offspring specific symptoms. CONCLUSIONS: Our findings indicate that parental genetics influences offspring cognition and educational attainment by genetic and phenotypic pathways, suggesting the expression of parental phenotypes partially explain the association between parental genetic risk and offspring outcomes. Multiple mediations might represent an effective approach to disentangle distinct pathways for intergenerational transmission of behavioral traits.

Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth.

Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain Cognitive Development Study® (ABCD). Across both discovery and replication sub-samples, we found that child reports of caregiver monitoring (supervision or regular knowledge of the child's whereabouts) were positively associated with general cognition abilities, after covarying for age, sex, household income, neighborhood deprivation, and parental education. This association was specific to the type of caregiving behavior (caregiver monitoring, but not caregiver warmth), and was most strongly associated with a broad domain of general cognition (but not executive function or learning/memory). Additionally, we found that caregiver monitoring partially mediated the association between household income and cognition, furthering our understanding of how socioeconomic disparities may contribute to disadvantages in cognitive development. Together, these findings underscore the influence of differences in caregiving behavior in shaping youth cognition. RESEARCH HIGHLIGHTS: Caregiver monitoring, but not caregiver warmth, is associated with cognitive performance in youth Caregiver monitoring partially mediates the association between household income and cognition Results replicated across two large matched samples from the Adolescent Brain Cognitive Development Study® (ABCD).

Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

Diminished insulin sensitivity is associated with altered brain activation to food cues and with risk for obesity - Implications for individuals born small for gestational age.

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.

A computational network perspective on pediatric anxiety symptoms.

BACKGROUND: While taxonomy segregates anxiety symptoms into diagnoses, patients typically present with multiple diagnoses; this poses major challenges, particularly for youth, where mixed presentation is particularly common. Anxiety comorbidity could reflect multivariate, cross-domain interactions insufficiently emphasized in current taxonomy. We utilize network analytic approaches that model these interactions by characterizing pediatric anxiety as involving distinct, inter-connected, symptom domains. Quantifying this network structure could inform views of pediatric anxiety that shape clinical practice and research. METHODS: Participants were 4964 youths (ages 5-17 years) from seven international sites. Participants completed standard symptom inventory assessing severity along distinct domains that follow pediatric anxiety diagnostic categories. We first applied network analytic tools to quantify the anxiety domain network structure. We then examined whether variation in the network structure related to age (3-year longitudinal assessments) and sex, key moderators of pediatric anxiety expression. RESULTS: The anxiety network featured a highly inter-connected structure; all domains correlated positively but to varying degrees. Anxiety patients and healthy youth differed in severity but demonstrated a comparable network structure. We noted specific sex differences in the network structure; longitudinal data indicated additional structural changes during childhood. Generalized-anxiety and panic symptoms consistently emerged as central domains. CONCLUSIONS: Pediatric anxiety manifests along multiple, inter-connected symptom domains. By quantifying cross-domain associations and related moderation effects, the current study might shape views on the diagnosis, treatment, and study of pediatric anxiety.

Measuring strengths and weaknesses in dimensional psychiatry.

BACKGROUND: The Extended Strengths and Weaknesses Assessment of Normal Behavior (E-SWAN) reconceptualizes each diagnostic criterion for selected DSM-5 disorders as a behavior, which can range from high (strengths) to low (weaknesses). Initial development focused on Panic Disorder, Social Anxiety, Major Depression, and Disruptive Mood Dysregulation Disorder. METHODS: Data were collected from 523 participants (ages 6-17). Parents completed each of the four E-SWAN scales and traditional unidirectional scales addressing the same disorders. Distributional properties, Item Response Theory Analysis (IRT), and Receiver Operating Characteristic (ROC) curves were used to assess and compare the performance of E-SWAN and traditional scales. RESULTS: In contrast to the traditional scales, which exhibited truncated distributions, all four E-SWAN scales had symmetric distributions. IRT analyses indicate the E-SWAN subscales provided reliable information about respondents throughout the population distribution; traditional scales only provided reliable information about respondents at the high end of the distribution. Predictive value for DSM-5 diagnoses was comparable to prior scales. CONCLUSIONS: E-SWAN bidirectional scales can capture the full spectrum of the population distribution of behavior underlying DSM disorders. The additional information provided can better inform examination of inter-individual variation in population studies, as well as facilitate the identification of factors related to resiliency in clinical samples.

Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

OBJECTIVE: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Problematic internet use in children and adolescents: associations with psychiatric disorders and impairment.

BACKGROUND: Problematic internet use (PIU) is an increasingly worrisome issue, as youth population studies are establishing links with internalizing and externalizing problems. There is a need for a better understanding of psychiatric diagnostic profiles associated with this issue, as well as its unique contributions to impairment. Here, we leveraged the ongoing, large-scale Child Mind Institute Healthy Brain Network, a transdiagnostic self-referred, community sample of children and adolescents (ages 5-21), to examine the associations between PIU and psychopathology, general impairment, physical health and sleep disturbances. METHODS: A total sample of 564 (190 female) participants between the ages of 7-15 (mean = 10.80, SD = 2.16), along with their parents/guardians, completed diagnostic interviews with clinicians, answered a wide range of self-report (SR) and parent-report (PR) questionnaires, including the Internet Addiction Test (IAT) and underwent physical testing as part of the Healthy Brain Network protocol. RESULTS: PIU was positively associated with depressive disorders (SR: aOR = 2.43, CI: 1.22-4.74, p = .01; PR: aOR = 2.56, CI: 1.31-5.05, p = .01), the combined presentation of ADHD (SR: aOR = 1.91, CI: 1.14-3.22, p = .01; PR: n.s.), Autism Spectrum Disorder (SR: n.s.; PR: aOR = 2.24, CI: 1.34-3.73, p < .001), greater levels of impairment (SR: Standardized Beta = 4.63, CI: 3.06-6.20, p < .001; PR: Standardized Beta = 5.05, CI: 3.67-6.42, p < .001) and increased sleep disturbances (SR: Standardized Beta = 3.15, CI: 0.71-5.59, p = .01; PR: Standardized Beta = 3.55, CI: 1.34-5.75, p < .001), even when accounting for demographic covariates and psychiatric comorbidity. CONCLUSIONS: The association between PIU and psychopathology, as well as its impact on impairment and sleep disturbances, highlight the urgent need to gain an understanding of mechanisms in order to inform public health recommendations on internet use in U.S. youth.

From positive psychology to psychopathology: the continuum of attention-deficit hyperactivity disorder.

BACKGROUND: Integration of positive psychology into clinical research and treatment has been slow. This integration can be facilitated by the conceptualisation of mental disorders as the high, symptomatic extreme of continuous normal variation. This assumes that there is also a low, positive extreme, which is, however, unchartered territory. This study aims to examine how well current measures capture the low extreme of mental disorder continua, using attention-deficit hyperactivity disorder (ADHD) as an example. METHODS: The ability of three validated scales to capture ADHD as a continuous trait was examined using Item Response Theory in a sample of 9,882 adolescents from the UK population-representative Twins Early Development Study. These scales were: the Strengths and Weakness of ADHD Symptoms and Normal behaviour scale (SWAN), Strength and Difficulties Questionnaire (SDQ - hyperactivity subscale), and Conners' Parent Rating Scale (Conners). RESULTS: Only the SWAN reliably differentiated interindividual differences between participants lying at any level of the continuous ADHD latent trait, including the extreme low, positive end (z-scores from -3 to +3). The SDQ showed low reliability across the ADHD latent trait. In contrast, the Conners performed best at differentiating individuals scoring at or above the mean to the high symptomatic range (z-scores from 0 to +3). The SWAN was the only measure to provide indicators of 'positive mental health', endorsed in the presence of particularly good attentive abilities. CONCLUSIONS: Scales such as the SWAN that reliably capture ADHD as a continuous trait, including the positive end, are important for not missing meaningful variation in population-based studies. Indicators of positive mental health may be helpful in clinical practice, as positive attributes have been shown to directly influence as well as buffer negative effects of psychiatric symptoms.

Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder.

BACKGROUND: Although severe irritability is a predictor of future depression according to recent meta-analytic evidence, other mechanisms for this developmental transition remain unclear. In this study, we test whether deficits in emotion recognition may partially explain this specific association in youth with severe irritability, defined as disruptive mood dysregulation disorder (DMDD). METHODS: Participants aged 8-20 years (M = 13.3, SD = 2.8) included youth with DMDD, split by low depressive (DMDD/LD; n = 52) and high depressive (DMDD/HD; n = 25) symptoms, and healthy controls (HC; n = 39). A standardized computer task assessed emotion recognition of faces and voices of adults and children expressing happiness, fear, sadness, and anger. A Group (3) × Emotion (4) × Actor (2) × Modality (2) repeated measures analysis of covariance examined the number of errors and misidentification of emotions. Linear regression was then used to assess whether deficits in emotion recognition were predictive of depressive symptoms at a 1 year follow-up. RESULTS: DMDD/HD youth were more likely to interpret happy stimuli as angry and fearful compared to DMDD/LD (happy as angry: p = 0.018; happy as fearful: p = 0.008) and HC (happy as angry: p = 0.014; happy as fearful: p = 0.024). In youth with DMDD, the misidentification of happy stimuli as fearful was associated with higher depressive symptoms at follow-up (ß = 0.43, p = 0.017), independent of baseline depressive and irritability symptoms. CONCLUSIONS: Deficits in emotion recognition are associated, cross-sectionally and longitudinally, with depressive symptoms in youth with severe irritability. Future studies should examine the neural correlates that contribute to these associations.

Association between attention bias to threat and anxiety symptoms in children and adolescents.

BACKGROUND: Considerable research links threat-related attention biases to anxiety symptoms in adults, whereas extant findings on threat biases in youth are limited and mixed. Inconsistent findings may arise due to substantial methodological variability and limited sample sizes, emphasizing the need for systematic research on large samples. The aim of this report is to examine the association between threat bias and pediatric anxiety symptoms using standardized measures in a large, international, multi-site youth sample. METHODS: A total of 1,291 children and adolescents from seven research sites worldwide completed standardized attention bias assessment task (dot-probe task) and child anxiety symptoms measure (Screen for Child Anxiety Related Emotional Disorders). Using a dimensional approach to symptomatology, we conducted regression analyses predicting overall, and disorder-specific, anxiety symptoms severity, based on threat bias scores. RESULTS: Threat bias correlated positively with overall anxiety symptoms severity (ß = 0.078, P = .004). Furthermore, threat bias was positively associated specifically with social anxiety (ß = 0.072, P = .008) and school phobia (ß = 0.076, P = .006) symptoms severity, but not with panic, generalized anxiety, or separation anxiety symptoms. These associations were not moderated by age or gender. CONCLUSIONS: These findings indicate associations between threat bias and pediatric anxiety symptoms, and suggest that vigilance to external threats manifests more prominently in symptoms of social anxiety and school phobia, regardless of age and gender. These findings point to the role of attention bias to threat in anxiety, with implications for translational clinical research. The significance of applying standardized methods in multi-site collaborations for overcoming challenges inherent to clinical research is discussed.

Association between irritability and bias in attention orienting to threat in children and adolescents.

BACKGROUND: Irritability, a frequent complaint in children with psychiatric disorders, reflects increased predisposition to anger. Preliminary work in pediatric clinical samples links irritability to attention bias to threat, and the current study examines this association in a large population-based sample. METHODS: We studied 1,872 children (ages 6-14) using the Development and Well-Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL), and dot-probe tasks. Irritability was defined using CBCL items that assessed temper tantrums and hot temper. The dot-probe task assessed attention biases for threat-related (angry face) stimuli. Multiple regression analysis was used to assess specificity of associations to irritability when adjusting for demographic variables and co-occurring psychiatric traits. Propensity score matching analysis was used to increase causal inference when matching for demographic variables and co-occurring psychiatric traits. RESULTS: Irritability was associated with increased attention bias toward threat-related cues. Multiple regression analysis suggests associations between irritability and threat bias are independent from demographic variables, anxiety, and externalizing traits (attention-deficit/hyperactivity, conduct, and headstrong/hurtful), but not from broad internalizing symptoms. Propensity score matching analysis indicated that this association was found for irritable versus nonirritable groups matched on demographic and co-occurring traits including internalizing symptoms. CONCLUSIONS: Irritability in children is associated with biased attention toward threatening information. This finding, if replicated, warrants further investigation to examine the extent to which it contributes to chronic irritability and to explore possible treatment implications.

Psychopathology and friendship in children and adolescents: disentangling the role of co-occurring symptom domains with serial mediation models.

The consolidation of social friendship groups is a vital part of human development. The objective of this study is to understand the direct and indirect influences of three major symptomatic domains-emotional, hyperkinetic, and conduct-on friendship. Specifically, we aim to study if the associations of one domain with friendship may be mediated by co-occurring symptoms from another domain. A total of 2512 subjects aged 6-14 years participated in this study. Friendship was evaluated by the Development and Well-Being Assessment's friendship section. We evaluated two main constructs as outcomes: (1) social isolation and (2) friendship latent construct. Emotional, hyperkinetic, and conduct symptomatic domains were evaluated with the Strengths and Difficulties Questionnaire (SDQ). All SDQ domains were positively associated with social isolation and negatively associated with friendship latent construct in univariate analysis. However, serial mediation models showed that the association between conduct domains with social isolation was mediated by emotion and hyperkinetic domains. Moreover, the associations between emotional and hyperkinetic domains with friendship latent construct in non-isolated children were mediated by the conduct domain. Emotion and hyperkinetic domains were directly and indirectly associated with social isolation, whereas conduct was directly and indirectly associated with overall friendship in non-isolated children. Results suggest that interventions aimed to improve social life in childhood and adolescence may have stronger effects if directed towards the treatment of emotion and hyperkinetic symptoms in socially isolated children and directed towards the treatment of conduct symptoms in children with fragile social connections.

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.

Serum copeptin in children exposed to maltreatment.

AIM: Childhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation; however, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. METHODS: This study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. RESULTS: Children exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. CONCLUSION: CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect.

Attentional bias to threat in children at-risk for emotional disorders: role of gender and type of maternal emotional disorder.

Previous studies suggested that threat biases underlie familial risk for emotional disorders in children. However, major questions remain concerning the moderating role of the offspring gender and the type of parental emotional disorder on this association. This study addresses these questions in a large sample of boys and girls. Participants were 6-12 years old (at screening) typically developing children participating in the High Risk Cohort Study for Psychiatric Disorders (n = 1280; 606 girls, 674 boys). Children were stratified according to maternal emotional disorder (none; mood disorder; anxiety disorder; comorbid anxiety/mood disorder) and gender. Attention biases were assessed using a dot-probe paradigm with threat, happy and neutral faces. A significant gender-by-parental emotional disorder interaction predicted threat bias, independent of anxiety and depression symptoms in children. Daughters of mothers with an emotional disorder showed increased attention to threat compared with daughters of disorder-free mothers, irrespective of the type of maternal emotion disorder. In contrast, attention bias to threat in boys only occurred in mothers with a non-comorbid mood disorder. No group differences were found for biases for happy-face cues. Gender and type of maternal emotional disorder predict attention bias in disorder-free children. This highlights the need for longitudinal research to clarify whether this pattern of threat-attention bias in children relates to the risk of developing anxiety and mood disorders later in life.