Megan Klabunde

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.

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, Cohens 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.

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.

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.

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.

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. Hum Brain Mapp 36:4135–4143, 2015.

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

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.

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.

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.

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.