Probing midbrain dopamine function in pediatric obsessive-compulsive disorder via neuromelanin-sensitive magnetic resonance imaging.

Obsessive-compulsive disorder (OCD) is an impairing psychiatric condition, which often onsets in childhood. Growing research highlights dopaminergic alterations in adult OCD, yet pediatric studies are limited by methodological constraints. This is the first study to utilize neuromelanin-sensitive MRI as a proxy for dopaminergic function among children with OCD. N = 135 youth (6-14-year-olds) completed high-resolution neuromelanin-sensitive MRI across two sites; n = 64 had an OCD diagnosis. N = 47 children with OCD completed a second scan after cognitive-behavioral therapy. Voxel-wise analyses identified that neuromelanin-MRI signal was higher among children with OCD compared to those without (483 voxels, permutation-corrected p = 0.018). Effects were significant within both the substania nigra pars compacta (p = 0.004, Cohen's d = 0.51) and ventral tegmental area (p = 0.006, d = 0.50). Follow-up analyses indicated that more severe lifetime symptoms (t = -2.72, p = 0.009) and longer illness duration (t = -2.22, p = 0.03) related to lower neuromelanin-MRI signal. Despite significant symptom reduction with therapy (p < 0.001, d = 1.44), neither baseline nor change in neuromelanin-MRI signal associated with symptom improvement. Current results provide the first demonstration of the utility of neuromelanin-MRI in pediatric psychiatry, specifically highlighting in vivo evidence for midbrain dopamine alterations in treatment-seeking youth with OCD. Neuromelanin-MRI likely indexes accumulating alterations over time, herein, implicating dopamine hyperactivity in OCD. Given evidence of increased neuromelanin signal in pediatric OCD but negative association with symptom severity, additional work is needed to parse potential longitudinal or compensatory mechanisms. Future studies should explore the utility of neuromelanin-MRI biomarkers to identify early risk prior to onset, parse OCD subtypes or symptom heterogeneity, and explore prediction of pharmacotherapy response.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Altered prefrontal activation during the inhibition of eating responses in women with bulimia nervosa.

BACKGROUND: The sense of 'loss of control' (LOC), or a feeling of being unable to stop eating or control what or how much one is eating, is the most salient aspect of binge eating. However, the neural alterations that may contribute to this experience and eating behavior remain poorly understood. METHODS: We used functional near-infrared spectroscopy (fNIRS) to measure activation in the prefrontal cortices of 23 women with bulimia nervosa (BN) and 23 healthy controls (HC) during two tasks: a novel go/no-go task requiring inhibition of eating responses, and a standard go/no-go task requiring inhibition of button-pressing responses. RESULTS: Women with BN made more commission errors on both tasks. BN subgroups with the most severe LOC eating (n = 12) and those who felt most strongly that they binge ate during the task (n = 12) showed abnormally reduced bilateral ventromedial prefrontal cortex (vmPFC) and right ventrolateral prefrontal cortex (vlPFC) activation associated with eating-response inhibition. In the entire BN sample, lower eating-task activation in right vlPFC was related to more frequent and severe LOC eating, but no group differences in activation were detected on either task when this full sample was compared with HC. BN severity was unrelated to standard-task activation. CONCLUSIONS: Results provide initial evidence that diminished PFC activation may directly contribute to more severe eating-specific control deficits in BN. Our findings support vmPFC and vlPFC dysfunction as promising treatment targets, and indicate that eating-specific tasks and fNIRS may be useful tools for identifying neural mechanisms underlying dysregulated eating.

Pandemic beyond the virus: maternal COVID-related postnatal stress is associated with infant temperament.

BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Subcortical shape in pediatric and adult obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) implicates alterations in cortico-striato-thalamo-cortical and fronto-limbic circuits. Building on prior structural findings, this is the largest study to date examining subcortical surface morphometry in OCD. METHODS: Structural magnetic resonance imaging data were collected from 200 participants across development (5-55 years): 28 youth and 75 adults with OCD and 27 psychiatrically healthy youth and 70 adults. General linear models were used to assess group differences and group-by-age interactions on subcortical shape (FSL FIRST). RESULTS: Compared to healthy participants, those with OCD exhibited surface expansions on the right nucleus accumbens and inward left amygdala deformations, which were associated with greater OCD symptom severity ([Children's] Yale-Brown Obsessive-Compulsive Scale). Group-by-age interactions indicated that accumbens group differences were driven by younger participants and that right pallidum shape was associated inversely with age in healthy participants, but not in participants with OCD. No differences in the shape of other subcortical regions or in volumes (FreeSurfer) were detected in supplementary analyses. CONCLUSIONS: This study is the largest to date examining subcortical shape in OCD and the first to do so across the developmental spectrum. NAcc and amygdala shape deformation builds on extant neuroimaging findings and suggests subtle, subregional alterations beyond volumetric findings. Results shed light on morphometric alterations in OCD, informing current pathophysiological models.

Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour.

Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder.

Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD (n = 36) and healthy participants (n = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected P < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen's d = 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = -2.99; 43.61% of total effect; P = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.

Non-suicidal Self-injurious Thoughts and Behaviors Among Adolescent Inpatients.

Non-suicidal self-injury (NSSI) is a serious public health concern that typically onsets during early adolescence. Adolescents (N = 980, ages 12-19 years) admitted for acute, residential psychiatric treatment completed baseline clinical interviews assessing mental disorders and questionnaires measuring demographics, early life adversity, and symptom severity. Prevalence rates of NSSI for lifetime (thoughts: 78%; behaviors: 72%), past year (thoughts: 74%; behaviors: 65%), and past month (thoughts: 68%; behaviors: 51%) were high. Although effect sizes were modest, the presence of a lifetime depressive disorder, sexual abuse, and comorbidity (i.e., three or more current disorders) were significant correlates of experiencing NSSI thoughts and behaviors. Furthermore, lifetime depressive disorder, current anxiety disorder, and comorbidity were associated with a greater odds of persistent NSSI thoughts and/or behaviors. Longitudinal studies are needed to determine whether targeting these factors reduces the persistence of NSSI thoughts and behaviors.

Altered fronto-amygdalar functional connectivity predicts response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Based on findings from adults with obsessive-compulsive disorder (OCD), this study examined alterations in resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA-vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first-line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning-a probable mechanism of action of E/RP. METHODS: Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age- and sex-matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12-16-week E/RP intervention for OCD. Participants were rescanned after the 12-16-week period. ANCOVAs tested group differences in baseline rs-fc. Cross-lagged panel models examined relationships between BLA-vmPFC rs-fc and OCD symptoms pre- and posttreatment. All tests were adjusted for participants' age, sex, and head motion. RESULTS: Right BLA-vmPFC rs-fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA-vmPFC rs-fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to posttreatment. CONCLUSIONS: These results provide further evidence of the BLA-vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD. METHODS: Twenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix. RESULTS: Thinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness. CONCLUSIONS: The current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.

Erosive pustular dermatosis of the scalp.

Erosive pustular dermatosis of the scalp (EPDS) is a rare inflammatory condition commonly associated with antecedent iatrogenic insult. EPDS may be diagnostically challenging owing to a lack of pathognomonic histologic findings and cutaneous manifestations that overlap with alternative dermatologic conditions. Therefore, EPDS may be more common than previously recognized. We present a 60-year-old woman with a four-year history of non-healing scalp erosions, progressive skin atrophy, and scarring alopecia despite intravenous antibiotics and intraoperative debridement who improved with systemic glucocorticoids. Our report emphasizes the importance of early recognition of EPDS when delayed wound healing and erosive disease occur in the setting of iatrogenic injury to the scalp. Timely treatment with systemic anti-inflammatory agents is paramount to prevent cicatricial alopecia and mitigate further scalp insult in EPDS.

Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa.

This study aimed to determine whether functional disturbances in fronto-striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict-related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto-striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto-striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto-striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit-based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions.

Altered frontal interhemispheric and fronto-limbic structural connectivity in unmedicated adults with obsessive-compulsive disorder.

BACKGROUND: Previous diffusion tensor imaging (DTI) studies of obsessive-compulsive disorder (OCD) have primarily used voxel- or tract-based methods to assess white matter microstructure in medicated patients. This is the first probabilistic tractography study to assess the structural connectivity of all major white matter tracts in unmedicated adults with OCD without comorbid psychopathology. We hypothesized that OCD compared to healthy participants would show reduced integrity in frontal interhemispheric and fronto-limbic tracts. METHODS: DTI data from 29 unmedicated adults with OCD were compared to that of 27 matched healthy control (HC) participants. TRACULA was used to assess probabilistic tractography and compare groups in the average fractional anisotropy (FA) of 8 bilateral tracts plus forceps minor and major, and explore group differences in axial (AD), radial (RD), and mean (MD) diffusivities in tracts where FA differed across groups. RESULTS: Significantly less FA was detected in OCD compared to HC participants in forceps minor, interhemispheric fibers of the frontal cortex, and right uncinate fasciculus (UNC), association fibers connecting frontal and limbic regions (p's < .05). FA in forceps minor was inversely associated with symptom severity in the OCD participants. Exploratory analyses revealed less AD in right UNC was inversely associated with OCD symptoms. CONCLUSIONS: Structural connectivity of frontal interhemispheric and fronto-limbic circuits may be altered in unmedicated adults with OCD, especially those with the most severe symptoms. These findings suggest a microstructural basis for the abnormal function and reduced resting-state connectivity of frontal regions and fronto-limbic circuits in OCD.

A longitudinal functional magnetic resonance imaging study of task control circuits and bulimic symptoms over adolescence.

BACKGROUND: Previous cross-sectional findings from adolescents and adults with Bulimia Nervosa (BN) suggest disturbances in fronto-striatal and cingulo-opercular task control circuits that support self-regulatory processes, including the resolution of cognitive conflict. Herein, we used longitudinal data to examine the developmental trajectories of such disturbances and how the functioning of these circuits relates to changes in BN symptoms over adolescence. METHODS: Thirty-two adolescent females with BN symptoms and 28 healthy control (HC) adolescents participated in the study. Functional magnetic resonance images (fMRI) during performance of a Simon task were acquired at three time points within 2-year intervals over adolescence. From the initial sample, 70% and 30% of the participants completed the second and third time points, respectively. Participants who completed all study time points did not differ from those lost to attrition on baseline demographic characteristics or any outcome measures. Using a region-of-interest approach, growth curve models tested group differences in the trajectory of conflict-related activation in task control circuits over time. Cross-lagged panel models examined transactional relationships between conflict-related activation in the same regions and BN symptoms over time. RESULTS: Growth curve models revealed different trajectories of conflict-related activation in right task control regions across BN and HC adolescents, such that HC but not BN adolescents showed activation decreases over time. These group differences were greatest when including only the BN adolescents whose symptoms remitted over time. Cross-lagged panel models revealed that less frequent bulimic episodes at first follow-up predicted later increases in conflict-related activation in bilateral task control regions. CONCLUSIONS: These longitudinal findings suggest overengagement of task control circuits in BN adolescents, especially those most resilient to persistent illness. Such overengagement may compensate for regulatory disturbances, allowing them to regulate eating behaviors over development. Thus, task control circuits may constitute targets for early interventions that enhance self-regulatory control.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. METHODS: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. LIMITATIONS: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. CONCLUSION: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. METHODS: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. LIMITATIONS: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. CONCLUSION: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Amygdala sub-regional functional connectivity predicts anxiety in children with reading disorder.

Pediatric reading disorder (RD) is associated with an increased risk of anxiety symptoms, yet understudied are the neurobiological factors that might underlie anxiety in children with RD. Given the role of the amygdala in anxiety, we assessed resting state functional connectivity of amygdalar subregions in children with RD to identify functional correlates of anxiety and reading impairment. We collected resting state functional MRI data from 22 children with RD and 21 typically developing (TD) children, ages 7 to 13 years. We assessed group differences in resting state functional connectivity (RSFC) from amygdalar subregions. Associations of amygdalar RSFC and volume with reading impairment, reading fluency scores, and anxiety symptoms were explored. Relative to TD children, those with RD showed increased RSFC from amygdalar nuclei to medial prefrontal cortex. Across all subjects, RSFC from right centromedial amygdala to left medial prefrontal cortex positively predicted both reading impairment and self-reported anxiety, and anxiety mediated the relationship between RSFC and reading impairment. These findings are consistent with amygdalar functional abnormalities in pediatric anxiety disorders, suggesting a common neurobiological mechanism underlying anxiety and reading impairment in children. Thus, aberrant patterns of RSFC from amygdalar subregions may serve as potential targets for the treatment of anxiety symptoms that typically co-occur with RD. Our dimensional approach to studying anxiety in RD revealed how amygdalar connectivity underlies anxiety and reading impairment across a continuum from normal to abnormal.