Alterations in Neural Activation During Facial Emotion Processing in Adolescent Male Participants With Klinefelter Syndrome.

OBJECTIVE: Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy (47,XXY), affecting 1 in 500 male participants. The phenotype of male participants with KS includes both physical features, such as tall stature and testicular insufficiency, and behavioral alterations, including difficulties in social functioning, anxiety, and depression. Studies examining underlying neural alterations associated with the behavioral phenotype, however, are sparse. We aimed to address this gap in knowledge using functional magnetic resonance imaging in conjunction with an emotion processing paradigm. METHOD: Functional magnetic resonance imaging was conducted on 38 children and adolescents with KS (Mage = 12.85, SD = 2.45) and 47 typical developing (control) boys (Mage = 12.04, SD = 1.82) as they completed a facial emotion processing task. Group differences in activation occurring during the processing of angry versus neutral faces were examined while controlling for age. RESULTS: The results indicated that relative to typically developing boys, boys with KS exhibited anomalous increases in activation of frontal, temporal, and occipital cortices. Within the KS group, secondary analyses indicated that greater activation in these regions was associated with more internalizing symptoms (e.g., anxiety, depression, withdrawn behaviors) and greater social impairments (e.g., social cognition, social communication, social motivation, social communication and interaction, functional communication). CONCLUSION: The findings from this study indicate a possible neural correlation for difficulties in social and emotional function in KS and add to a growing body of research aimed at increasing our understanding of neural biomarkers in this condition. Future studies that examine the influence of testosterone-replacement therapy on these differences are warranted.

Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder.

Postinfectious neuroinflammation has been implicated in multiple models of acute-onset obsessive-compulsive disorder including Sydenham chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.

Physiology and emotions: Within individual associations during caregiver-adolescent conflict.

Concordance between physiological and emotional responses is central to models of emotion and has been shown to correspond to effective responses and well-being in adults. A deeper understanding of physiological-emotional concordance during ecologically relevant scenarios is essential to then determine if these associations predict mental health problems or can serve as a helpful biomarker of risk or resilience in adults and youth. The present study assessed the minute-to-minute associations between sympathetic (i.e., skin conductance level [SCL]) and parasympathetic (i.e., respiratory sinus arrhythmia [RSA]) nervous system activity and self-reported emotions, assessed via video-mediated recall procedures, during a parent-adolescent conflict discussion task. Associations between emotion ratings and physiological activity were assessed in adolescents (N = 97; ages 10-15) and their adult caregivers (N = 97). Utilizing a multilevel modeling approach, findings demonstrated a significant positive association between SCL and emotion ratings for youth, suggesting that increased engagement and alertness contributed to more positive emotion. RSA was unrelated to emotion ratings. The presence of significant variability in associations indicated the presence of potential moderators. This could include clinically relevant processes (e.g., emotion regulation, relationship quality, and mental health). Future research should continue to build on findings to determine if, when, and for whom, physiological-emotional concordance occurs, and whether the degree of concordance predicts risk for mental and physical health problems.

Racial/ethnic differences in parenting behaviors among depressed parents.

Low parental warmth and high control are associated with parental depression and with the development of depression in children. The majority of this research, however, has focused on non-Hispanic White (NHW) parents. The present study tested whether parenting behaviors differed by race/ethnicity in a sample (N = 169) of parents with a history of depression. Participants were drawn from a randomized trial designed to prevent depression in at-risk adolescents (ages 9-15 years old). All participating parents had a current or past depressive episode within the youth's lifetime. Parents self-classified as 67.5% NHW, 17.2% Latinx (LA), and 15.4% Black (BL). Youths and parents completed standardized positive and negative interaction tasks; trained raters coded the videotaped interactions for parental warmth and control. Analyses examined the impact of race/ethnicity, current parent depression symptoms, context of the discussion (positive/negative task), and demographic covariates on observed parenting behaviors. Results revealed significant interactions among race/ethnicity, depression, and task type. Differences in warmth and control between racial/ethnic groups were more likely to be observed in negative interactions and when parents' depression symptoms were lower. In these circumstances, BL parents were rated as higher in control and lower in warmth than NHW parents. Results add to the literature on racial/ethnic differences in parenting among parents with a history of depression and highlight the importance of assessing parenting in context to capture more subtle patterns of interactions between parents and offspring. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neuroinflammation in Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome.

Sydenham chorea (SC), pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are postinfectious neuroinflammatory diseases that involve the basal ganglia and have obsessive-compulsive disorder as a major manifestation. As is true for many childhood rheumatological diseases and neuroinflammatory diseases, SC, PANDAS and PANS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. Research on the treatment of these disorders depend on three complementary modes of intervention including: treating the symptoms, treating the source of inflammation, and treating disturbances of the immune system. Future studies should aim to integrate neuroimaging, inflammation, immunogenetic, and clinical data (noting the stage in the clinical course) to increase our understanding and treatment of SC, PANDAS, PANS, and all other postinfectious/immune-mediated behavioral disorders.

Mean-level correspondence and moment-to-moment synchrony in adolescent and parent affect: Exploring associations with adolescent age and internalizing and externalizing symptoms.

Interactions with parents are integral in shaping the development of children's emotional processes. Important aspects of these interactions are overall (mean level) affective experience and affective synchrony (linkages between parent and child affect across time). Respectively, mean-level affect and affective synchrony reflect aspects of the content and structure of dyadic interactions. Most research on parent-child affect during dyadic interactions has focused on infancy and early childhood; adolescence, however, is a key period for both normative emotional development and the emergence of emotional disorders. We examined affect in early to mid-adolescents (N = 55, Mage = 12.27) and their parents using a video-mediated recall task of 10-min conflict-topic discussions. Using multilevel modeling, we found evidence of significant level-2 effects (mean affect) and level-1 effects (affective synchrony) for parents and their adolescents. Level-2 and level-1 associations were differentially moderated by adolescent age and adolescent internalizing and externalizing symptoms. More specifically, parent-adolescent synchrony was stronger when adolescents were older and had more internalizing problems. Further, more positive adolescent mean affect was associated with more positive parent affect (and vice versa), but only for dyads with low adolescent externalizing problems. Results underscore the importance of additional research examining parent-child affect in adolescence.

Resting State Psychophysiology in Youth with OCD and Their Caregivers: Preliminary Evidence for Trend Synchrony and Links to Family Functioning.

The burden of OCD in children and adolescents extends to their caregivers. Prior work in other disorders and unaffected youth has found synchrony in psychophysiological arousal for youth-caregiver dyads. This preliminary study explored whether psychophysiological trend synchrony in youth-caregiver dyads (N = 48) occurred and was moderated by youth OCD diagnosis. We also explored whether psychophysiological indices (i.e., electrodermal activity, heart rate, respiratory sinus arrhythmia) were correlated with reported family functioning in the OCD subsample (n = 25). Youth with OCD had higher resting heart rate than unaffected peers; this was not replicated in caregivers. Trend synchrony was found across the full sample of dyads for electrodermal activity and heart rate, with no moderation by diagnostic group. In the OCD group, youth heart rate was correlated with family conflict and caregiver heart rate with expressiveness. Findings provide preliminary support for further examination of heart rate and family factors in OCD-affected youth and their caregivers.

Adverse childhood experiences, parenting, and socioeconomic status: Associations with internalizing and externalizing symptoms in adolescence.

BACKGROUND: Adverse childhood experiences (ACEs), low socioeconomic status (SES), and harsh parenting practices each represent well-established risk factors for mental health problems. However, research supporting these links has often focused on only one of these predictors and psychopathology, and interactions among these variables in association with symptoms are not well understood. OBJECTIVE: The current study utilized a cross-sectional, multi-informant, and multi-method design to investigate the associations of ACEs, SES, parenting, and concurrent internalizing and externalizing problems in adolescents. PARTICIPANTS AND SETTING: Data are from a volunteer sample of 97 adolescents and their caregivers recruited from 2018 to 2021 in a southern U.S. metropolitan area to sample a range of exposure to ACEs. METHODS: Multiple linear regression models were used to assess associations among adolescents' ACEs exposure, SES, observed parenting practices, and symptoms of internalizing and externalizing psychopathology. RESULTS: Lower SES was associated with higher levels of internalizing and externalizing symptoms, while higher ACEs exposure and observed parenting were related to externalizing but not internalizing symptoms. Associations of adolescents' exposure to physical abuse and perceived financial insecurity with externalizing symptoms were moderated by warm and supportive parenting behaviors. Conversely, harsh parenting was linked to increased levels of externalizing symptoms, particularly in the context of low income. CONCLUSIONS: Findings suggest that the presence of multiple risk factors may incur greater vulnerability to externalizing problems, while warm and supportive parenting practices may provide a buffer against externalizing problems for adolescents exposed to physical abuse. Links between ACEs, SES, parenting, and youth adjustment should continue to be explored, highlighting parenting as a potentially important and malleable intervention target.

Does Parenting Explain the Link Between Cumulative SES Risk and Child Problems in the Context of Parental Depression?

The accumulation of socioeconomic stressors, such as being a single parent and having a limited income, is associated with childhood maladjustment and prospective poor health. Evidence suggests both positive and negative parenting strategies (e.g., warmth and praise; criticism and neglect) may account for the relationship between socioeconomic adversity and child outcomes. However, despite the common co-occurrence of parental depression and socioeconomic stress, models of cumulative socioeconomic risk and parenting have yet to be tested in parents who are also coping with depression. In a sample of children whose parents have a history of depression, this study extends findings from a previous report (i.e., Sullivan et al. in J Fam Psychol 33:883-893, 2019) to test whether behavioral observations of parenting account for the association between a cumulative risk index of socioeconomic stress and child psychological problems in the same sample of 179 children (Mage = 11.46 years, SDage = 2.00) of parents with depression. Both positive and negative parenting accounted for the relationship between socioeconomic risk and both child- and parent-reported externalizing problems, whereas no evidence emerged for parenting accounting for the relation between cumulative risk and internalizing problems. This study highlights the central role socioeconomic stress plays in child maladjustment among parents coping with depression, as well as how parenting may be a critical mechanism linking socioeconomic stress and child externalizing problems.

Shared and unique neural mechanisms underlying pediatric trichotillomania and obsessive compulsive disorder.

BACKGROUND: Little is known about the neural underpinnings of pediatric trichotillomania (TTM). We examined error-related negativity (ERN)-amplitude and theta-EEG power differences among youth with TTM, OCD, and healthy controls (HC). METHODS: Forty channel EEG was recorded from 63 pediatric participants (22 with TTM, 22 with OCD, and 19 HC) during the Eriksen Flanker Task. EEG data from inhibitory control were used to derive estimates of ERN amplitude and event-related spectral power associated with motor inhibition. RESULTS: TTM and HC were similar in brain activity patterns in frontal and central regions and TTM and OCD were similar in the parietal region. Frontal ERN-amplitude was significantly larger in OCD relative to TTM and HC, who did not differ from each other. The TTM group had higher theta power compared to OCD in frontal and central regions, and higher theta than both comparison groups in right motor cortex and superior parietal regions. Within TTM, flanker task performance was correlated with EEG activity in frontal, central, and motor cortices whereas global functioning and impairment were associated with EEG power in bilateral motor and parietal cortices. CONCLUSIONS: Findings are discussed in terms of shared and unique neural mechanisms in TTM and OCD and treatment implications.

Comparison of three models of adverse childhood experiences: Associations with child and adolescent internalizing and externalizing symptoms.

Exposure to adverse childhood experiences (ACEs) is prevalent and confers risk for psychopathology later in life. Approaches to understanding the impact of ACEs on development include the independent risk approach, the Dimensional Model of Adversity and Psychopathology (DMAP) distinguishing between threat and deprivation events, and the cumulative risk approach. The present research provides an empirical confirmation of DMAP and a comparison of these three approaches in predicting internalizing and externalizing symptoms in youth. In Study 1, mental health professionals (N = 57) rated ACEs as threat or deprivation events. These ratings were used to create composites to represent the DMAP approach in Study 2. With cross-sectional and longitudinal data from children and adolescents in state custody (N = 23,850), hierarchical linear regression analyses examined independent risk, DMAP, and cumulative risk models in predicting internalizing symptoms, disinhibited externalizing symptoms, and antagonistic externalizing symptoms. All three approaches produced significant models and revealed associations between exposure to ACEs and symptoms. Individual risk accounted for significantly more variance in symptoms than cumulative risk and DMAP. Cumulative risk masked differential associations between ACEs and psychological symptoms found in the individual risk and DMAP approaches. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neurochemical correlates of behavioral treatment of pediatric trichotillomania.

BACKGROUND: Trichotillomania (TTM) is a chronic and impairing psychiatric disorder with suspected dysfunctional cortico-striato-thalamo-cortical (CSTC) circuit activity reflecting excitatory/inhibitory signaling imbalance. TTM neurochemistry is understudied, with no prior research using magnetic resonance spectroscopy (MRS). This pilot investigation examined associations between TTM diagnosis, symptom severity, and response to behavioral treatment with MRS neurometabolites glutamate (Glu) and γ-aminobutyric acid (GABA) in CSTC structures. METHODS: Proton echo-planar spectroscopic imaging (PEPSI) MRS was acquired from bilateral pregenual anterior cingulate cortex (pACC), caudate, putamen, globus pallidus, thalamus, and proximal white matter in 10 unmedicated girls with TTM, ages 9-17 years, before and after treatment, and from 13 age- and sex-matched healthy controls. RESULTS: Nine of 10 TTM patients were treatment responders. Pretreatment mean Glu and GABA did not differ significantly between participants and controls. Pretreatment TTM symptoms were correlated with Glu in (left + right) pACC (r = 0.88, p = 0.02) and thalamus (r = 0.82, p = 0.012), and were negatively correlated with pACC GABA (r = -0.84, p = 0.034). Mean GABA in putamen increased 69% (baseline to post-treatment) (p = 0.027). Higher pretreatment Glu in caudate, putamen, globus pallidus, and thalamus predicted greater symptom decreases with treatment (all r < -0.6, p < 0.05); higher caudate GABA predicted less treatment-related symptom decline (r = 0.86, p = 0.014). LIMITATIONS: Small sample, GABA quantified with spectral fitting rather than editing. CONCLUSION: Consistent with other neuroimaging, MRS reveals discrete CSTC chemical changes with effective behavior therapy, and possibly with TTM etiology. TTM symptoms relate to excess excitatory versus inhibitory signaling in pACC and thalamus; symptom improvement may reflect reduced excitatory drive of the CSTC direct-pathway activity.

Predictors of placement disruptions in foster care.

BACKGROUND: Many children who are removed from a dangerous or neglectful home and placed in state custody subsequently experience additional disruptions while in custody, which can compound the effects of ongoing stress and instability. As such, placement stability has been identified as a critical objective and a key indicator of success for children residing in substitutive care. OBJECTIVE: To examine the utility of child protective services data in identifying predictors of placement disruption. PARTICIPANTS AND SETTING: The current study examined data from youth in Tennessee state custody who had been assessed using the Child and Adolescent Needs and Strengths (CANS) assessment within 30-days of their first, out-of-home placement. The sample included 8,853 youth ages 5-19 years old (M = 13.1; SD = 4.0; 44.8 % female). METHODS: Demographics, placement information, and the CANS assessment were collected by the Tennessee Department of Children's Services for all child welfare episodes for children as part of the system's usual standard of care. Bivariate correlation and linear regression models were conducted. RESULTS: Multiple risk indices from the CANS appeared to significantly increase risk of placement disruption, including child internalizing and externalizing symptoms, school difficulties, youth affect dysregulation, and child age. CONCLUSIONS: The current findings suggest that data collected as part of standard practice by child welfare workers such as the CANS is both feasible and has utility for identifying sources of risk for placement disruptions and to inform possible targets of intervention to enhance placement stability.

Family functioning in pediatric trichotillomania, obsessive compulsive disorder, and healthy comparison youth.

Pediatric trichotillomania (TTM) is an understudied condition that can be highly impairing; little is known about family environmental features that shape its development and course. We examined family functioning among age and gender-matched groups of youth with primary TTM (n = 30; mean age = 12.87), obsessive compulsive disorder (OCD; n = 30; mean age = 12.70), and no psychiatric history (healthy controls; HC; n = 30; mean age = 12.46). An additional group of n = 25 TTM cases was employed to examine relationships between TTM severity and family functioning. All youth completed standardized diagnostic assessment, including the Family Environment Scale (FES) and Children's Report of Parenting Behavior Inventory (CRPBI). Family functioning was more impaired among both TTM and OCD cases relative to controls, as evidenced by higher levels of child-reported FES conflict and lower cohesion, expressiveness, and organization. Less consistent findings emerged on parent report, with cohesion, but not conflict, distinguishing the HC and clinical groups. In keeping with prior research, parents of TTM-affected youth also reported lower expressiveness and cohesion than parents in the OCD group. There was limited evidence for links between hair-pulling severity and family impairment and no links to parenting behavior. Findings are discussed in terms of implications for family focused treatment.

Cumulative socioeconomic status risk and observations of parent depression: Are there associations with child outcomes?

Parental depression (Goodman et al., 2011) and low socioeconomic status (SES) are important risk factors for child maladjustment. Further, depression and low SES are linked; low SES adults are more likely to experience depression. Whereas studies commonly covary out noise associated with SES variability, research on the association of SES with child outcomes after controlling for parental depression is limited. This study aimed to extend the literature by observing parent depressive affect and evaluating the relationship between cumulative SES risk and child problems as well as whether child gender moderates this association using multigroup nested model comparisons. Findings suggested that cumulative SES risk status explained significant variance in child- and parent-reported internalizing problems and parent-reported externalizing problems after accounting for observed parent depressive affect. Of importance, child gender moderated 2 of these significant findings (i.e., child-reported internalizing and parent-reported externalizing behaviors), such that girls, but not boys, were at higher risk of problems in the context of high cumulative SES risk. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Coping and Stress Reactivity as Moderators of Maternal Depressive Symptoms and Youth's Internalizing and Externalizing Symptoms.

Youth's responses to stress are a central feature of risk and resilience across development. The current study examined whether youth coping and stress reactivity moderate the association of current maternal depressive symptoms with youth's internalizing and externalizing symptoms. Mothers (Mage = 41.58, SD = 6.18) with a wide range of depressive symptoms and their children ages 9-15 (Mage = 12.25, SD = 1.89, 45.3% girls) completed measures of youth symptoms and coping and automatic responses to stress. Mothers also completed a self-report measure of depressive symptoms. Youth's primary and secondary control coping, stress reactivity, and involuntary disengagement moderated the association between current maternal depressive symptoms and youth symptoms. Maternal depressive symptoms were associated with youth's internalizing and externalizing symptoms when youth used low as opposed to high levels of primary and secondary control coping. Conversely, maternal depressive symptoms were associated with youth symptoms for youth with high levels of stress reactivity and involuntary disengagement. The findings suggest interventions focused on improving the use of primary and secondary control coping skills and reducing reactivity and involuntary disengagement to stress may benefit youth with mothers who are experiencing high levels of depressive symptoms.

Laboratory and Self-Report Methods to Assess Reappraisal and Distraction in Youth.

Coping and emotion regulation are central features of risk and resilience in childhood and adolescence, but research on these constructs has relied on different methods of assessment. The current study aimed to bridge the gap between questionnaire and experimental methods of measuring secondary control coping strategies, specifically distraction and cognitive reappraisal, and examine associations with symptoms of anxiety and depression in youth. A community sample of 70 youth (ages 9-15) completed a novel experimental coping and emotion regulation paradigm and self-report measures of coping and emotion regulation and symptoms. Findings indicate that use of distraction and reappraisal during the laboratory paradigm was associated with lower levels of negative emotion during the task. Youth emotion ratings while implementing distraction, but not reappraisal, during the laboratory task were associated with youth self-reported use of secondary control coping in response to family stress. Youth symptoms of anxiety and depression were also significantly positively associated with negative emotion ratings during the laboratory task, and both laboratory task and self-reported coping and emotion regulation accounted for significant variance in symptoms in youth. Both questionnaire and laboratory methods to assess coping and emotion regulation in youth are important for understanding these processes as possible mechanisms of risk and resilience and continued integration of these methods is a priority for future research.

The tell-tale heart: physiological reactivity during resolution of ambiguity in youth anxiety.

In the past decade, cognitive biases and physiological arousal have each been proposed as mechanisms through which paediatric anxiety develops and is maintained over time. Preliminary studies have found associations between anxious interpretations of ambiguity, physiological arousal, and avoidance, supporting theories that link cognition, psychophysiology, and behaviour. However, little is known about the relationship between youths' resolutions of ambiguity and physiological arousal during acute stress. Such information may have important clinical implications for use of verbal self-regulation strategies and cognitive restructuring during treatments for paediatric anxiety. In this brief report, we present findings suggesting that anxious, but not typically developing, youth select avoidant goals via non-threatening resolution of ambiguity during a stressor, and that this resolution of ambiguity is accompanied by physiological reactivity (heart rate, heart rate variability, and respiratory sinus arrhythmia). We propose future empirical research on the interplay between interpretation bias, psychophysiology, and child anxiety, as well as clinical implications.

Parent reports of children's working memory, coping, and emotional/behavioral adjustment in pediatric brain tumor patients: A pilot study.

Neurocognitive problems in childhood survivors of brain tumors are well documented. Further, research has shown that problems in cognitive functioning may be associated with impairment in the use of complex strategies needed to cope with stress, including secondary control coping strategies (e.g., acceptance and cognitive reappraisal) which have been associated with fewer adjustment problems. The present study measured cognitive function, coping strategies, and adjustment in children ages 6-16 years at the time of brain tumor diagnosis and at two follow-up time-points up to 1 year post-diagnosis. In a prospective design, working memory was assessed in a total of 29 pediatric brain tumor patients prior to undergoing surgery, child self-reported coping was assessed at 6 months post-diagnosis, and parent-reported child adjustment was assessed at 12 months post-diagnosis. Significant correlations were found between working memory difficulties and secondary control coping. Secondary control coping was also negatively correlated with child attention and total problems. Regression analyses did not support secondary control coping mediating the association between working memory difficulties and child attention or total problems. These findings represent the first longitudinal assessment of the association between working memory, coping, and adjustment across the first year of a child's brain tumor diagnosis and suggest a possible role for early interventions addressing both working memory difficulties and coping in children with brain tumors.

Glutamate in Pediatric Obsessive-Compulsive Disorder and Response to Cognitive-Behavioral Therapy: Randomized Clinical Trial.

Cognitive-behavioral therapy (CBT) is effective for pediatric obsessive-compulsive disorder (OCD), but non-response is common. Brain glutamate (Glu) signaling may contribute to OCD pathophysiology and moderate CBT outcomes. We assessed whether Glu measured with magnetic resonance spectroscopy (MRS) was associated with OCD and/or CBT response. Youths aged 7-17 years with DSM-IV OCD and typically developing controls underwent 3 T proton echo-planar spectroscopic imaging (PEPSI) MRS scans of pregenual anterior cingulate cortex (pACC) and ventral posterior cingulate cortex (vPCC)-regions possibly affected by OCD-at baseline. Controls returned for re-scan after 8 weeks. OCD youth-in a randomized rater-blinded trial-were re-scanned after 12-14 weeks of CBT or after 8 weeks of minimal-contact waitlist; waitlist participants underwent a third scan after crossover to 12-14 weeks of CBT. Forty-nine children with OCD (mean age 12.2±2.9 years) and 29 controls (13.2±2.2 years) provided at least one MRS scan. At baseline, Glu did not differ significantly between OCD and controls in pACC or vPCC. Within controls, Glu was stable from scan-to-scan. Within OCD subjects, a treatment-by-scan interaction (p=0.034) was observed, driven by pACC Glu dropping 19.5% from scan-to-scan for patients randomized to CBT, with minor increases (3.8%) for waitlist participants. The combined OCD participants (CBT-only plus waitlist-CBT) also showed a 16.2% (p=0.004) post-CBT decrease in pACC Glu. In the combined OCD group, within vPCC, lower pre-CBT Glu predicted greater post-CBT improvement in symptoms (CY-BOCS; r=0.81, p=0.00025). Glu may be involved in the pathophysiology of OCD and may moderate response to CBT.