A Functional Magnetic Resonance Imaging Meta-Analysis of Childhood Trauma.

BACKGROUND: Traumatic experiences during childhood significantly impact the developing brain and contribute to the development of numerous physical and mental health problems. To date, however, a comprehensive understanding of the functional impairments within the brain associated with childhood trauma histories does not exist. Previous functional magnetic resonance imaging (fMRI) meta-analytical tools required homogeneity of task types and the clinical populations studied, thus preventing the comprehensive pooling of brain-based deficits present in children who have trauma histories. We hypothesized that the use of the novel, data-driven Bayesian author-topic model approach to fMRI meta-analyses would reveal deficits in brain networks that span fMRI task types in children with trauma histories. METHODS: To our knowledge, this is the first study to use the Bayesian author-topic model approach to fMRI meta-analyses within a clinical population. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we present data-driven results obtained by combining activation patterns across heterogeneous tasks from 1428 initially screened studies and combining data from 14 studies that met study criteria (285 children with trauma histories, 297 healthy control children). RESULTS: Altered brain activity was revealed within 2 clusters in children with trauma histories compared to control children: the default mode/affective network/posterior insula and the central executive network. Our identified clusters were associated with tasks pertaining to cognitive processing, emotional/social stress, self-referential thought, memory, unexpected stimuli, and avoidance behaviors in youths who have experienced childhood trauma. CONCLUSIONS: Our results reveal disturbances in children with trauma histories within the modulation of the default mode and central executive networks-but not the salience network-regardless of whether children also presented with posttraumatic stress symptoms.

Do verbal coaching cues and analogies affect motor skill performance in youth populations?

PURPOSE: The way coaching cues are worded can impact on the quality with which a subsequent motor skill is executed. However, there have been few investigations on the effect of coaching cues on basic motor skill performance in youths. METHOD: Across several international locations, a series of experiments were undertaken to determine the effect of external coaching cues (EC), internal coaching cues (IC), analogies with a directional component (ADC) and neutral control cues on sprint time (20 m) and vertical jump height in youth performers. These data were combined using internal meta-analytical techniques to pool results across each test location. This approach was amalgamated with a repeated-measures analysis to determine if there were any differences between the ECs, ICs and ADCs within the different experiments. RESULTS: 173 participants took part. There were no differences between the neutral control and experimental cues in any of the internal meta-analyses except where the control was superior to the IC for vertical jump (d = -0.30, [-0.54, -0.05], p = 0.02). Just three of eleven repeated-measures analyses showed significant differences between the cues at each experimental location. Where significant differences were noted, the control cue was most effective with some limited evidence supporting the use of ADCs (d = 0.32 to 0.62). CONCLUSION: These results suggest the type of cue or analogy provided to a youth performer has little subsequent effect on sprint or jump performance. Accordingly, coaches might take a more specific approach that is suited to the level or preferences of a particular individual.

Longitudinal investigation of cognition, social competence, and anxiety in children and adolescents with Turner syndrome.

Turner syndrome (TS), a common neurogenetic disorder caused by complete or partial absence of an X chromosome in females, is characterized by distinct physical, cognitive, and social-emotional features. Girls with TS typically display average overall intellectual functioning with relative strength in verbal abilities and weaknesses in visuospatial processing, executive function (EF), and social cognition. This study was designed to better understand longitudinal trajectories of cognitive and social-emotional domains commonly affected in TS. Participants included 57 girls with monosomic 45,X TS and 55 age- and verbal-IQ matched girls who completed behavioral, child-report, and parent-report measures across four timepoints. Group differences in visuospatial processing, EF, social cognition, and anxiety were assessed longitudinally. Potential effects of estrogen replacement therapy (ERT) were assessed cross-sectionally on an exploratory basis. The TS group showed poorer performance on measures of visuospatial processing, EF, and social cognition, but not anxiety, compared to controls throughout childhood and adolescence. There were no significant group differences in the trajectory of skill development over time. Exploratory analyses within the TS group revealed that girls who were receiving ERT showed better performance on measures of overall IQ, expressive vocabulary, and visuospatial processing compared to those not receiving ERT. Consistent with existing literature, weaknesses in visuospatial processing, EF, and social competence among girls with TS persisted throughout childhood and adolescence. Exploratory analyses suggest that ERT may help improve some aspects of cognitive function in TS, although other pre-existing, nonhormonal differences between the two TS subgroups may alternatively explain these findings, given our study design. Future studies are needed to examine potential impacts of ERT on cognitive and social-emotional development in TS.

How effective are external cues and analogies in enhancing sprint and jump performance in academy soccer players?

This study investigated the effect of external (EC) and internal coaching cues (IC), analogies with a directional component (ADC) on sprint (20 m) and vertical jump performance in academy soccer players (n = 20). A repeated-measures analysis, with post-hoc comparisons, was used to identify any differences between these cues and a neutral (control) cue. Significant differences were found for both sprint (p < 0.001) and jump (p = 0.022) comparisons among cue types. In post-hoc analyses for the 20 m sprint, significant differences were observed between the EC and the IC, favouring the EC (p < 0.01, ES = 1.27 [CI: 0.24, 2.30]), and "away" ADC and the IC, favouring the "away" ADC (p < 0.01, ES = 1.21 [CI: 0.19, 2.22]). No other cues showed significant differences. For vertical jump, there was just one significant difference between comparisons, that being for the "away" ADC vs. the neutral cue, favouring the latter (p = 0.023, ES = 0.4 [CI: -0.04 to 0.84]). It appears that ECs and ADCs are most effective when coaching sprinting performance in academy soccer players. However, simply encouraging maximal effort from a youth athlete also appears to be a reasonable cueing strategy to drive performance in youth athletes.

Effect of sex chromosome number variation on attention-deficit/hyperactivity disorder symptoms, executive function, and processing speed.

AIM: To study sex differences in attention-deficit/hyperactivity disorder (ADHD) symptoms, we explored whether X chromosome absence or excess is independently associated with deficits in attention and hyperactivity, executive function, and processing speed. METHOD: We assessed 116 children (ages 3y 10mo-11y 11mo, mean 8y 5mo, SD 1y 11mo) with a variable number of sex chromosomes: 36 females with Turner syndrome (45, X0), 20 males with Klinefelter syndrome (47, XXY), 37 typically developing females (XX), and 23 typically developing males (XY). RESULTS: X chromosome absence was associated with increased attention problems, hyperactivity, and deficits in inhibitory control, compared with female children with XX (all p<0.003). Conversely, X chromosome excess was associated with weakness in working memory (p=0.018) and approached significance for attention problems (p=0.071) but not with hyperactivity, or weakness in inhibitory control relative to male children with XY. Using non-parametric effect size to quantify the clinical effect revealed that X chromosome absence affected attention, hyperactivity, executive function, and processing speed (all r>0.4), while X excess affected in-laboratory as well as parent-reported working memory (all r>0.4). INTERPRETATION: Our observations provide compelling evidence that the absence or excess of an X chromosome distinctly affects cognition and behaviors associated with ADHD.

On the relationship between mathematics and visuospatial processing in Turner syndrome.

A common neurocognitive phenotype of Turner syndrome (TS) includes coincident deficits in math and visuospatial reasoning while overall IQ remains intact. However, research has highlighted disparities in the relationship between these properties in women with TS, suggesting that not all visuospatial domains are equally related to mathematics in this group. Here, we present findings from a longitudinal investigation of visuospatial processing and its relationship to math performance in adolescent girls with TS and age-matched healthy controls. Participants completed a standardized battery of math and visuospatial tests once a year for 4 years. Linear mixed effects modeling was used to examine the relationship between mathematics and each visuospatial domain over time. Our results indicate that math performance was related to visual tracking, visual-motor coordination, and figure-ground processing. Such visuospatial domains appear to be uniquely affected by TS and could contribute to their deficits in math performance. Furthermore, differences in math and visuospatial test performance between girls with TS and healthy controls remain stable over time. Our results have important implications for the role of visuospatial processing in early math performance and may inform the development of effective interventions aimed at improving math education in children with TS.

An interoceptive model of bulimia nervosa: A neurobiological systematic review.

The objective of our study was to examine the neurobiological support for an interoceptive sensory processing model of bulimia nervosa (BN). To do so, we conducted a systematic review of interoceptive sensory processing in BN, using the PRISMA guidelines. We searched PsychInfo, Pubmed, and Web of Knowledge databases to identify biological and behavioral studies that examine interoceptive detection in BN. After screening 390 articles for inclusion and conducting a quality assessment of articles that met inclusion criteria, we reviewed 41 articles. We found that global interoceptive sensory processing deficits may be present in BN. Specifically there is evidence of abnormal brain function, structure and connectivity in the interoceptive neural network, in addition to gastric and pain processing disturbances. These results suggest that there may be a neurobiological basis for global interoceptive sensory processing deficits in BN that remain after recovery. Data from taste and heart beat detection studies were inconclusive; some studies suggest interoceptive disturbances in these sensory domains. Discrepancies in findings appear to be due to methodological differences. In conclusion, interoceptive sensory processing deficits may directly contribute to and explain a variety of symptoms present in those with BN. Further examination of interoceptive sensory processing deficits could inform the development of treatments for those with BN.

The moderating effects of sex on insula subdivision structure in youth with posttraumatic stress symptoms.

BACKGROUND: The insula is involved in interoceptive processing, emotion awareness, and attention to salient stimuli. Research suggests that these functions are specific-albeit overlapping-within insula subdivisions. Additional studies also imply that sexual dimorphism and different rates of development occur within these subdivisions in youth. The purpose of this study was to examine potential insula subdivision structure differences in youth with PTSD symptoms as compared to controls and test sex as a moderator of these differences. METHODS: Insula structure (volume, surface area, and thickness) was measured with structural magnetic resonance imaging (sMRI) and calculated using Freesurfer software. We compared insula structure across age- and sex-matched boys and girls with (30 with and 29 without) PTSD symptoms while also controlling for age and whole brain measurements. RESULTS: Differences were specific to the insula's anterior circular sulcus. Within this subregion, boys with PTSD symptoms demonstrated larger volume and surface area than control boys, while girls with PTSD symptoms demonstrated smaller volume and surface area than control girls. DISCUSSION: Findings indicate a potential neurobiological explanation for sex differences in youth with PTSD symptoms.

Examining the neural correlates of emergent equivalence relations in fragile X syndrome.

The neural mechanisms underlying the formation of stimulus equivalence relations are poorly understood, particularly in individuals with specific learning impairments. As part of a larger study, we used functional magnetic resonance imaging (fMRI) while participants with fragile X syndrome (FXS), and age- and IQ-matched controls with intellectual disability, were required to form new equivalence relations in the scanner. Following intensive training on matching fractions to pie charts (A=B relations) and pie charts to decimals (B=C relations) outside the scanner over a 2-day period, participants were tested on the trained (A=B, B=C) relations, as well as emergent symmetry (i.e., B=A and C=B) and transitivity/equivalence (i.e., A=C and C=A) relations inside the scanner. Eight participants with FXS (6 female, 2 male) and 10 controls, aged 10-23 years, were able to obtain at least 66.7% correct on the trained relations in the scanner and were included in the fMRI analyses. Across both groups, results showed that the emergence of symmetry relations was correlated with increased brain activation in the left inferior parietal lobule, left postcentral gyrus, and left insula, broadly supporting previous investigations of stimulus equivalence research in neurotypical populations. On the test of emergent transitivity/equivalence relations, activation was significantly greater in individuals with FXS compared with controls in the right middle temporal gyrus, left superior frontal gyrus and left precuneus. These data indicate that neural execution was significantly different in individuals with FXS than in age- and IQ-matched controls during stimulus equivalence formation. Further research concerning how gene-brain-behavior interactions may influence the emergence of stimulus equivalence in individuals with intellectual disabilities is needed.

Neural correlates of self-injurious behavior in Prader-Willi syndrome.

Individuals with Prader-Willi syndrome (PWS), a genetic disorder caused by mutations to the q11-13 region on chromosome 15, commonly show severe skin-picking behaviors that can cause open wounds and sores on the body. To our knowledge, however, no studies have examined the potential neural mechanisms underlying these behaviors. Seventeen individuals with PWS, aged 6-25 years, who showed severe skin-picking behaviors, were recruited and scanned on a 3T scanner. We used functional magnetic resonance imaging (fMRI) while episodes of skin picking were recorded on an MRI-safe video camera. Three participants displayed skin picking continuously throughout the scan, three participants did not display skin picking, and the data for one participant evidenced significant B0 inhomogeneity that could not be corrected. The data for the remaining 10 participants (six male, four female) who displayed a sufficient number of picking and nonpicking episodes were subjected to fMRI analysis. Results showed that regions involved in interoceptive, motor, attention, and somatosensory processing were activated during episodes of skin-picking behavior compared with nonpicking episodes. Scores obtained on the Self-Injury Trauma scale were significantly negatively correlated with mean activation within the right insula and left precentral gyrus. These data indicate that itch and pain processes appear to underlie skin-picking behaviors in PWS, suggesting that interoceptive disturbance may contribute to the severity and maintenance of abnormal skin-picking behaviors in PWS. Implications for treatments are discussed.

Post-traumatic stress and age variation in amygdala volumes among youth exposed to trauma.

Theoretically, normal developmental variation in amygdala volumes may be altered under conditions of severe stress. The purpose of this article was to examine whether posttraumatic stress moderates the association between age and amygdala volumes in youth exposed to traumatic events who are experiencing symptoms of post-traumatic stress disorder (PTSD). Volumetric imaging was conducted on two groups of youth aged 9-17 years: 28 with exposure to trauma and PTSD symptoms (boys = 15, girls = 13) and 26 matched (age, IQ) comparison youth (Controls; boys = 12, girls = 14). There was a significant group by age interaction in predicting right amygdala volumes. A positive association between age and right amygdala volumes was observed, but only in PTSD youth. These associations with age remained when controlling for IQ, total brain volumes and sex. Moreover, older youth with PTSD symptoms had relatively larger right amygdala volumes than controls. Findings provide evidence that severe stress may influence age-related variation in amygdala volumes. Results further highlight the importance of utilizing age as an interactive variable in pediatric neuroimaging research, in so far as age may act as an important moderator of group differences.

Second-Generation Antipsychotic Drugs in Anorexia Nervosa: A Meta-Analysis of Randomized Controlled Trials.

Background: Second-generation antipsychotic drugs (SGAs) are increasingly administered to achieve weight gain in anorexia nervosa. In this meta-analysis, we aimed to determine if any evidence for this treatment option can be derived from randomized controlled trials (RCTs). Methods: Based on the 'World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders', a systematic update literature search was applied to identify all RCTs investigating the efficacy, acceptability, and tolerability of SGAs in anorexia nervosa in comparison to placebo/no treatment. The primary outcome was weight gain measured by mean change in body mass index (BMI). Secondary outcomes were mean changes in Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS) total score and Eating Disorders Inventory (EDI) total score and premature discontinuation of treatment. Employing a random-effects model standardized mean differences based on Hedges's g and Mantel-Haenszel risk ratios were calculated. Results: Seven RCTs (n = 201) investigating olanzapine (N = 4), quetiapine (N = 2), and risperidone (N = 1) were included. We found no statistically significant between-group differences for mean BMI change when pooling the SGAs (N = 7, n = 161; Hedges's g = 0.13, 95% CI: -0.17 to 0.43; p = 0.4) and when examining the individual drugs. Furthermore, the SGAs failed to differentiate statistically significantly from placebo/no treatment for all secondary outcomes. Conclusions: Based on the current evidence, pharmacological treatment of anorexia nervosa with SGAs cannot be generally recommended although some individuals or subgroups of patients might benefit from an antipsychotic medication. Further research is required to identify which patients will likely benefit from such a treatment option. © 2015 S. Karger AG, Basel.

Central coherence in adolescents with bulimia nervosa spectrum eating disorders.

BACKGROUND: Weak central coherence-a tendency to process details at the expense of the gestalt-has been observed among adults with bulimia nervosa (BN) and is a potential candidate endophenotype for eating disorders (EDs). However, as BN behaviors typically onset during adolescence it is important to assess central coherence in this younger age group to determine whether the findings in adults are likely a result of BN or present earlier in the evolution of the disorder. This study examines whether the detail-oriented and fragmented cognitive inefficiency observed among adults with BN is observable among adolescents with shorter illness duration, relative to healthy controls. METHOD: The Rey-Osterrieth Complex Figure Test (RCFT) was administered to a total of 47 adolescents with DSM5 BN, 42 with purging disorder (PD), and 25 healthy controls (HC). Performance on this measure was compared across the three groups. RESULTS: Those with BN and PD demonstrated significantly worse accuracy scores compared to controls in the copy and delayed recall condition with a moderate effect size. These findings were exacerbated when symptoms of BN increased. DISCUSSION: Poorer accuracy scores reflect a fragmented and piecemeal strategy that interferes with visual-spatial integration in BN spectrum disorders. This cognitive inefficiency likely contributes to broad difficulties in executive functioning in this population especially in the context of worsening bulimic symptoms. The findings of this study support the hypothesis that poor global integration may constitute a cognitive endophenotype for BN.

Interoceptive sensitivity deficits in women recovered from bulimia nervosa.

Self-report studies suggest that patients with bulimia nervosa (BN) evidence difficulties with interoceptive awareness. Indeed, interoceptive deficits may persist after recovery of BN and may be a biological trait that predisposes symptom development in BN. However, no studies to date have directly assessed interoceptive sensitivity, or accuracy in detecting and perceiving internal body cues, in patients with or recovered from BN. Nine women who had recovered from BN and 10 healthy control women completed the Heart Beat Perception Task (HBPT) in which individuals were required to estimate the number of heartbeats between intervals of time. Accuracy scores were compared between groups. Significant differences were found between the groups on the HBPT ((F1,19) = 7.78, p = .013, Cohen's d = 1.16) when controlling for age. These results suggest that deficits in interoceptive sensitivity are present in individuals recovered from BN. Thus interoceptive deficits may be one factor that bridges the gap between brain dysfunction and symptom presentation in BN.

Altered insula activation during pain anticipation in individuals recovered from anorexia nervosa: evidence of interoceptive dysregulation.

OBJECTIVE: Recent evidence raises the possibility that symptoms of anorexia nervosa (AN) could be related to impaired interoception. Pain is an interoceptive process with well-characterized neuroanatomical pathways that may overlap to a large degree with neural systems that may be dysregulated in individuals with AN, such as the insula. METHOD: Functional magnetic resonance imaging (fMRI) was used to assess neural substrates of pain anticipation and processing in 10 healthy control women (CW) and 12 individuals recovered from AN (REC AN) in order to avoid the confounding effects of malnutrition. Painful heat stimuli were applied while different colors signaled the intensity of the upcoming stimuli. RESULTS: REC AN compared with CW showed greater activation within right anterior insula (rAI), dorsolateral prefrontal cortex (dlPFC) and cingulate during pain anticipation, and greater activation within dlPFC and decreased activation within posterior insula during painful stimulation. Greater anticipatory rAI activation correlated positively with alexithymic feelings in REC AN participants. DISCUSSION: REC AN showed a mismatch between anticipation and objective responses, suggesting altered integration and, possibly, disconnection between reported and actual interoceptive state. Alexithymia assessment provided additional evidence of an altered ability to accurately perceive bodily signals in women recovered from AN.

Double-blind placebo-controlled trial of quetiapine in anorexia nervosa.

OBJECTIVE: Our objective is to determine whether quetiapine was superior to placebo in increasing weight or reducing core symptoms of anorexia nervosa as assessed by the Yale-Brown-Cornell Eating Disorder Scale and the Eating Disorder Inventory-2. METHOD: Participants were randomised to 8 weeks of quetiapine or placebo. RESULTS: There are 21 participants who signed informed consent, 15 were randomised, 14 returned for at least one visit after receiving drug and 10 completed the study. There were no differences between drug and placebo in questionnaire scores, weight or measures of anxiety or depression. DISCUSSION: There was no difference between quetiapine and placebo on weight gain or core symptoms. Small effect sizes suggest that a higher number of participants would not increase significant differences between groups.

Differential weight restoration on olanzapine versus fluoxetine in identical twins with anorexia nervosa.

OBJECTIVE: No studies have compared the response to selective serotonin reuptake inhibitors and atypical antipsychotics in anorexia nervosa. This case study examines such a comparison. METHOD: This report describes a case of 12-year-old identical twins with anorexia nervosa, one of whom was treated with olanzapine and the other with fluoxetine, while undergoing family therapy. RESULTS: Twin A treated with fluoxetine went from 75 to 84.4% ideal body weight, while Twin B treated with olanzapine went from 72 to 99.9% ideal body weight over the course of 9 months. DISCUSSION: This case supports the need for adequately powered, controlled clinical trials to test the efficacy of olanzapine in adolescents presenting with anorexia nervosa.