Compelling evidence indicates that disruption in functional connectivity (FC) in brain networks underlies many psychiatric and developmental disorders. Current theory posits that biological (i.e., cortisol) and environmental (i.e., stress) experiences in early life are strong determinants in the development of functional brain systems and formative in the genesis of such disorders. The objective of this study was to examine the extent to which individual differences in cortisol concentrations during FC magnetic resonance imaging (MRI) would map onto variability in hippocampal to default mode network (DMN) connectivity in typically developing youth.Salivary cortisol and FC MRI data were collected concurrently in 33 scan-naive 7- to 15-year-old participants. Twenty-nine of these participants previously completed the Trier Social Stress Test. Hippocampal to DMN FC and endogenous cortisol variability during MRI were examined. A possible association between MRI cortisol and cortisol response to the Trier Social Stress Test during the preceding visit or a participant's ratings of anxiety during MRI was tested.There were significant positive relations between MRI cortisol levels and measurements in the following 3 areas: hippocampal to DMN FC during the resting state, cortisol levels during the Trier Social Stress Test, and fear/anxiety ratings during MRI. Fear/anxiety ratings during MRI also related to self-reported anxiety on standardized measurements.This study shows for the first time that FC of the hippocampus is altered with changing cortisol responsivity in youth. Altered FC during the resting state may represent altered alertness or monitoring resulting from variation in glucocorticoid function in youth, which carries implications for the effect of stress on response monitoring and decision making.

Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity.A total of 21 psychotropic medication-free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level-dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons.Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity.Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia. Findings support the incorporation of both categorical and dimensional approaches in neuropsychiatric research.

The effects of Israeli adolescents' exposure to rocket attacks over time were examined, focusing on anxiety, depression, aggression, and violence commission.A sample of 362 adolescents from southern Israel was followed from 2008 through 2011 with four annual assessments. Measures included exposure to rocket attacks (gauging whether children were affected by rocket attacks, both directly and indirectly, through friends and family), anxiety (items from the State Anxiety Inventory), depression (the Center for Epidemiological Studies Child Depression Scale), aggression (the Orpinas Aggression Scale), and violence commission (from the Social and Health Assessment).Concurrent and longitudinal findings differed. Wave 1 exposure to rockets attacks was associated with Wave 1 anxiety, depression, and aggression. Longitudinal results evinced only modest effects of exposure on anxiety and depression, no effects on aggression, but robust effects on violence commission. Exposure to terror attacks before the study predicted increased odds of violence commission at the fourth and final wave, controlling for violence commission at the first, second, and third wave. Exposure to rocket attacks in the second wave predicted increased odds of violence commission at the third wave.This is the first longitudinal study attesting to the prospective longitudinal effect of exposure to terrorism on adolescent violence. Findings should serve as a red flag for health care practitioners working in civil areas afflicted by terrorism and political violence.

To assess whether being bullied between 7 and 10 years of age is directly associated with self-harm in late adolescence when controlling for previous exposure to an adverse family environment (domestic violence, maladaptive parenting); concurrent internalizing and externalizing behavior; and subsequent psychopathology (borderline personality disorder and depression symptoms).A total of 4,810 children and adolescents in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort were assessed to ascertain bullying exposure (between 7 and 10 years of age) and self-harm at 16 to 17 years.A total of 16.5% of 16- to 17-year-olds reported self-harm in the previous year. Being bullied was associated with an increased risk of self-harm directly, and indirectly via depression symptoms in early adolescence. The association between an adverse family environment (exposure to maladaptive parenting and domestic violence) and self-harm was partially mediated by being bullied.Being bullied during childhood increases the risk of self-harm in late adolescence via several distinct pathways, for example, by increasing the risk of depression and by exacerbating the effects of exposure to an adverse family environment; as well as in the absence of these risk exposures. Health practitioners evaluating self-harm should be aware that being bullied is an important potential risk factor.

Children with prolonged grief reactions (PGR) have been found to be at increased risk for depression and functional impairment. Identifying and diagnosing PGR in children is challenging, as there are no available dimensional measures with established thresholds and no diagnostic criteria in the DSM-IV. We examine thresholds for the Inventory for Complicated Grief-Revised for Children (ICG-RC) and compare this dimensional approach to the proposed DSM-5 criteria for Persistent Complex Bereavement-Related Disorder. We also identify a screening tool for PGR.Parentally bereaved children and adolescents, 8 through 17 years of age, were assessed at 9, 21, and 33 months after parental death. Receiver operating characteristics were used to establish the "best threshold" that would identify youth with PGR and evaluate the proposed DSM-5 criteria cross-sectionally and longitudinally.A score of 68 or higher on the ICG-RC was found to have high sensitivity (0.942) and specificity (0.965) in differentiating cases of PGR from noncases at 9 months. We also identified a 6-item screening tool that consists of longing and yearning for the deceased, inability to accept the death, shock, disbelief, loneliness, and a changed world view. The proposed DSM-5 criteria correctly identified only 20% to 41.7% of cases with PGR at different time points.For the identification of youth at risk for PGR, the dimensional approach outperformed the proposed categorical diagnostic criteria. We propose a brief screening scale that, if validated, can help clinicians to identify bereaved children and adolescents at risk for PGR, and guide the development of prevention and intervention strategies.

To examine whether early menarche is associated with depressive symptoms from adolescence to young adulthood.The study is based on 3,648 girls from a large UK birth cohort (Avon Longitudinal Study of Parents and Children) who provided data on age at onset of menarche and at least 1 measure of depressive symptoms assessed using the Short Mood and Feelings Questionnaire at ages 13, 14, 16.5, 18, and 19 years. Depressive symptoms were examined as binary outcomes (sum score ≥11) and continuous latent traits (using confirmatory factor analysis). Results were adjusted for socioeconomic disadvantage, paternal absence, and body mass index (BMI).In early to midadolescence, there was strong evidence for increased odds of depressive symptoms in girls with early compared with late menarche. Differences remained after adjusting for confounders (adjusted odds ratio [OR] = 2.07, 95% confidence interval [CI] = 1.28-3.35 at 13 years; OR = 2.09, 95% CI = 1.41-3.09 at 14 years). At the later time points there was weak evidence for an association between early menarche and depressive symptoms in the unadjusted models. Adjusting for confounders explained a moderate amount of the effect (adjusted OR = 1.26, 95% CI = 0.86-1.85 at 16.5 years; OR = 1.33, 95% CI = 0.91-1.95 at 18 years; and OR = 1.40, 95% CI = 0.93-2.13 at 19 years). Findings were similar when we repeated the analysis using continuous depressive symptom latent traits.Girls who experience earlier menarche than their peers have increased levels of depressive symptoms in early to midadolescence, but there is little evidence for an effect of early menarche on depressive symptoms in later adolescence and young adulthood.

To examine the factors associated with the persistence of childhood gender dysphoria (GD), and to assess the feelings of GD, body image, and sexual orientation in adolescence.The sample consisted of 127 adolescents (79 boys, 48 girls), who were referred for GD in childhood (<12 years of age) and followed up in adolescence. We examined childhood differences among persisters and desisters in demographics, psychological functioning, quality of peer relations and childhood GD, and adolescent reports of GD, body image, and sexual orientation. We examined contributions of childhood factors on the probability of persistence of GD into adolescence.We found a link between the intensity of GD in childhood and persistence of GD, as well as a higher probability of persistence among natal girls. Psychological functioning and the quality of peer relations did not predict the persistence of childhood GD. Formerly nonsignificant (age at childhood assessment) and unstudied factors (a cognitive and/or affective cross-gender identification and a social role transition) were associated with the persistence of childhood GD, and varied among natal boys and girls.Intensity of early GD appears to be an important predictor of persistence of GD. Clinical recommendations for the support of children with GD may need to be developed independently for natal boys and for girls, as the presentation of boys and girls with GD is different, and different factors are predictive for the persistence of GD.

To describe current social functioning in a clinical sample of 60 adults with autism (mean age = 44 years) who were all of average nonverbal IQ (70+) when first diagnosed (mean age = 6.75 years).Outcome measures included standardized diagnostic and cognitive assessments and questionnaires on social functioning. Child and adult variables related to current outcomes were explored.All individuals continued to meet criteria for autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R), but severity of autism symptoms declined over time. Nevertheless, only 10 individuals (17%) were rated as having a "good" or "very good" outcome; the majority (60%) were assessed as having "poor" or "very poor" outcomes. The strongest predictor of adult outcome was the Reciprocal Social Interaction domain score on the ADI at diagnostic confirmation. Change over time was further examined in a subgroup (n = 44) previously assessed 20 years ago earlier (mean age = 26 years). Although severity of autism had continued to decrease during the adult period, social outcomes were poorer than in younger adulthood.In this cohort of adults first diagnosed with autism, on average, 37 years previously, social inclusion remains very limited, despite general improvements in autism symptomatology with age. Whether these findings will be replicated in future generations of children with autism, who now have the benefits of earlier diagnosis and wider access to specialist provision, needs to be the focus of further longitudinal research.