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Background: Since the publication of the DSM-IV in 1994, research on obsessive-compulsive disorder (OCD) has continued to expand. It is timely to reconsider the nosology of this disorder, assessing whether changes to diagnostic criteria as well as subtypes and specifiers may improve diagnostic validity and clinical utility.Methods: The existing criteria were evaluated. Key issues were identified. Electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for relevant studies.Results: This review presents a number of options and preliminary recommendations to be considered for DSM-V. These include: (1) clarifying and simplifying the definition of obsessions and compulsions (criterion A); (2) possibly deleting the requirement that people recognize that their obsessions or compulsions are excessive or unreasonable (criterion B); (3) rethinking the clinical significance criterion (criterion C) and, in the interim, possibly adjusting what is considered "time-consuming" for OCD; (4) listing additional disorders to help with the differential diagnosis (criterion D); (5) rethinking the medical exclusion criterion (criterion E) and clarifying what is meant by a "general medical condition"; (6) revising the specifiers (i.e., clarifying that OCD can involve a range of insight, in addition to "poor insight," and adding "tic-related OCD"); and (7) highlighting in the DSM-V text important clinical features of OCD that are not currently mentioned in the criteria (e.g., the major symptom dimensions).Conclusions: A number of changes to the existing diagnostic criteria for OCD are proposed. These proposed criteria may change as the DSM-V process progresses. [ABSTRACT FROM AUTHOR]

The presence of obsessive-compulsive disorder (OCD) has been linked to decreased quality of life (QoL) among adults, yet little is known about the impact of OCD on QoL in pediatric patients. Sixty-two youth with OCD and their parent(s) were administered the Children's Yale-Brown Obsessive Compulsive Scale following a clinical interview. Children completed the Pediatric Quality of Life Inventory and parents completed the Pediatric Quality of Life Parent Proxy Inventory and Child Behavior Checklist. QoL scores for OCD patients were significantly lower than for healthy controls, but similar to QoL in a general psychiatric sample on the majority of domains. Parent-child agreement on QoL was moderate to strong across age groups. Results indicate that, in youth with OCD, QoL is reduced relative to healthy controls, related to OCD symptom severity per parent-report, and are strongly predicted by the presence of comorbid externalizing and internalizing symptoms. [ABSTRACT FROM AUTHOR]

This report describes the development and psychometric properties of the Children's Florida Obsessive Compulsive Inventory (C-FOCI). Designed specifically as a brief measure for assessing obsessive-compulsive symptoms, the C-FOCI was created for use in both clinical and community settings. Study 1 included 82 children and adolescents diagnosed with primary Obsessive-Compulsive Disorder, and their parents. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was administered to assess symptom severity. Thereafter, parents completed the Child Obsessive-Compulsive Impact Scale-Parent Version and Child Behavior Checklist, and youth completed the C-FOCI, Child Obsessive-Compulsive Impact Scale-Child Version, Multidimensional Anxiety Scale for Children, and Children's Depression Inventory-Short Form. A subgroup of 21 individuals was retested with the C-FOCI after completing 14 sessions of intensive cognitive-behavioral therapy. Construct validity of the C-FOCI was supported vis-à-vis evidence of treatment sensitivity, and moderate relations with clinician-rated symptom severity, the CY-BOCS Symptom Checklist, child- and parent-rated functional impairment, child-rated anxiety, and parent-rated internalizing symptoms. Discriminant validity was evidenced by weak relationships with parent-reports of externalizing symptoms. For Study 2, 191 non-clinical adolescents completed the C-FOCI to assess the feasibility of internet administration. Overall, internal consistency was acceptable for the C-FOCI Symptom Checklist and Severity Scale, and respondents were able to complete the measure with little difficulty. Taken together, the findings of Studies 1 and 2 provide initial support for the reliability and validity of the C-FOCI for the assessment of pediatric obsessive-compulsive symptoms. [ABSTRACT FROM AUTHOR]

A reclassification of obsessive-compulsive disorder (OCD) into a new diagnostic category spectrum of "obsessive-compulsive spectrum disorders" (OCSDs) has recently been proposed, with considerable debate, for the forthcoming Diagnostic and Statistical Manual-Fifth Edition (DSM-V). This paper provides a critical analysis of the available empirical data regarding this conceptual and nosological shift. Specifically, we review research on shared commonalities and differences between OCD and the putative OCSDs in relation to their clinical presentation, phenotype, neurobiology, and treatment response. We conclude that a reclassification of OCD into a separate OCSD spectrum is premature and not supported by the currently available data. [ABSTRACT FROM AUTHOR]

Background: Recently, anterior limb of the internal capsule and nucleus accumbens deep brain stimulation (DBS) has been used in the treatment of medication-refractory obsessive-compulsive disorder (OCD). This region has been previously explored with lesion therapy, but with the advent of DBS there exists the possibility of monitoring the acute and chronic effects of electrical stimulation. The stimulation-induced benefits and side effects can be reversibly and blindly applied to a variety of locations in this region.Objective: To explore the acute effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region.Methods: Ten total DBS leads in five patients with chronic and severe treatment-refractory OCD were tested. Patients were examined 30 days after DBS placement and received either "sham" testing or actual testing of the acute effects of DBS (the alternative condition tested 30 days later).Results: Pooled responses were reviewed for comparability of distribution using standard descriptive methods, and relationships between the variables of interest were sought using chi2 analysis. A total of 845 stimulation trials across the five patients were recorded and pooled. Of these 16% were elicited from sham stimulation and 17% from placebo (0 V stimulation). A comparison of active to sham trials showed that sham stimulation was not associated with significant side effects or responses from patients. Non-mood-related responses were found to be significantly associated with the ventral lead contacts (0 and 1) (p = 0.001). Responses such as taste, smell and smile were strongly associated with the most ventral lead positions. Similarly, physiological responses--for example, autonomic changes, increased breathing rate, sweating, nausea, cold sensation, heat sensation, fear, panic and panic episodes--were significantly associated with ventral stimulation (p = 0.001). Fear and panic responses appeared clustered around the most ventral electrode (0). Acute stimulation resulted in either improved or worsened mood responses in both the dorsal and ventral regions of the anterior limb of the internal capsule.Conclusion: The acute effects of DBS in the region of the anterior limb of the internal capsule and nucleus accumbens, particularly when obtained in a blinded fashion, provide a unique opportunity to localise brain regions and explore circuitry. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a chronic, impairing condition with an estimated lifetime prevalence in adults of 2.5%. Controlled treatment trials have demonstrated that cognitive-behavioral therapy (CBT) is an effective intervention for OCD. However, many individuals diagnosed with OCD do not receive appropriate, empirically validated interventions, perhaps due to limited knowledge of CBT among mental health practitioners. This article provides a review of CBT for OCD. Issues related to treatment delivery and assessment are presented and highlighted by an individual example. [ABSTRACT FROM AUTHOR]

Background: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region.Objective: To investigate panic and fear resulting from DBS.Methods: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions.Results: DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off conditionConclusions: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) is clinically heterogeneous. Previous studies have reported different patterns of treatment response to serotonin reuptake inhibitors (SRI) based on symptom dimension. Our objective was to replicate these results in OCD patients who participated in one of four randomized, placebo-controlled, clinical trials (RCT).Methods: A total of 165 adult OCD subjects participated in one or more eight-week RCT with clomipramine, fluvoxamine, or fluoxetine. All subjects were classified as having major or minor symptoms in four specific OC symptom dimensions that were derived in a previous factor analytic study involving many of these same patients. Ordinal logistic regression was used to test the association between OC symptom dimensions and SRI response.Results: We found a significant association between the symptom dimension involving sexual, religious and harm-related obsessions as well as checking compulsions (AGG/SR) and improved SRI response. This increased rate of SRI response was experienced primarily by individuals with harm-related obsessions. Over 60% of patients with AGG/SR OCD symptoms were rated as very much improved after SRI treatment.Limitations: As some of the RCTs included were conducted prior to the development of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), improvement in OCD severity was assessed using the Clinical Global Improvement (CGI) Scale. Data from the double-blind and open-label continuation phases of these trials was collapsed together to increase statistical power.Conclusions: Patients with OCD vary in their response to SRIs. The presence of AGG/SR symptoms is associated with an initial positive response to SRIs. These data add to the growing body of work linking central serotonin systems with aggressive behavior. [ABSTRACT FROM AUTHOR]

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making., (© 2024. The Author(s).)

Anger outbursts (AO) are associated with severe symptoms, impairment and poorer treatment outcomes for anxious children, though limited research has examined AO in youth with co-occurring autism and anxiety disorders. This study examined AO in children with autism and anxiety by evaluating clinical characteristics, family accommodation, and changes in AO following anxiety-focused treatment. The sample comprised 167 youth with autism and anxiety enrolled in a multi-site randomized clinical trial comparing standard care CBT for anxiety, CBT adapted for youth with autism, and usual care. Most participants (60%) had AO, which contributed to impairment above and beyond anxiety and autism. AO impacted functional impairment indirectly through a pathway of parental accommodation. AO reduced with anxiety-focused treatment. Findings highlight that AO are common in this population and uniquely contribute to functional impairment, indicating a need for direct targeting in treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE exposure after OCD diagnosis. No significant associations between ACEs and comorbidity or CBT response were found, suggesting that CBT for pediatric OCD is effective regardless of ACE exposure. Family financial problems were associated with increased obsessive-compulsive symptom severity and negative thinking. Implications for research and practice are discussed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Recent advances in stereotactic and functional neurosurgery have brought forth the stereo-electroencephalography approach which allows deeper interrogation and characterization of the contributions of deep structures to neural and affective functioning. We argue that this approach can and should be brought to bear on the notoriously intractable issue of defining the pathophysiology of refractory psychiatric disorders and developing patient-specific optimized stimulation therapies., Methods: We have developed a suite of methods for maximally leveraging the stereo-electroencephalography approach for an innovative application to understand affective disorders, with high translatability across the broader range of refractory neuropsychiatric conditions., Results: This article provides a roadmap for determining desired electrode coverage, tracking high-resolution research recordings across a large number of electrodes, synchronizing intracranial signals with ongoing research tasks and other data streams, applying intracranial stimulation during recording, and design choices for patient comfort and safety., Conclusion: These methods can be implemented across other neuropsychiatric conditions needing intensive electrophysiological characterization to define biomarkers and more effectively guide therapeutic decision-making in cases of severe and treatment-refractory disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Background: Treatment-resistant depression (TRD) affects about 30% of individuals with major depressive disorder. Deep brain stimulation (DBS) is an investigational intervention for TRD with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side effect profiles., Methods: We conducted a systematic PubMed review following PRISMA guidelines. Seven randomized-controlled trials (n=198) and eight open-label trials (n=77) were included, spanning 2009-2020. Outcome measures included Hamilton Depression Rating Scale or Montgomery-Åsberg Depression Rating Scale scores, as well as response and remission rates over time. Outcomes were tracked at last follow-up and quantified as a time course using model-based network meta-analysis. Linear mixed models were fit to individual patient data to identify covariates., Results: DBS achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement around 23 months. There were no significant subgroup effects of stimulation target, time of last follow-up, sex, age of disease onset, or duration of disease, but open-label trials showed significantly greater treatment effects compared to randomized controlled trials. Long-term (12-60 month) response and remission rates were 48% and 35%, respectively. The time course of improvement with active stimulation could not be adequately distinguished from that with sham stimulation, when available., Conclusions: DBS produces significant chronic improvement in symptoms of TRD. The limited sham-controlled data, however, does not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy., (Copyright © 2024. Published by Elsevier Inc.)

Understanding the neural basis of major depressive disorder (MDD) is vital to guiding neuromodulatory treatments. The available evidence supports the hypothesis that MDD is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neural systems lead to diminished emotion regulation and intrusive ruminations. Recent research also points towards network changes in the brain, especially within the prefrontal cortex (PFC), as primary sources of MDD etiology. However, due to limitations in spatiotemporal resolution and clinical opportunities for intracranial recordings, this hypothesis has not been directly tested. We recorded intracranial EEG from the dorsolateral (dlPFC), orbitofrontal (OFC), and anterior cingulate cortices (ACC) in neurosurgical patients with MDD. We measured daily fluctuations in self-reported depression severity alongside directed connectivity between these PFC subregions. We focused primarily on delta oscillations (1-3 Hz), which have been linked to GABAergic inhibitory control and intracortical communication. Depression symptoms worsened when connectivity within the left vs. right PFC became imbalanced. In the left hemisphere, all directed connectivity towards the ACC, from the dlPFC and OFC, was positively correlated with depression severity. In the right hemisphere, directed connectivity between the OFC and dlPFC increased with depression severity as well. This is the first evidence that delta oscillations flowing between prefrontal subregions transiently increase intensity when people are experiencing more negative mood. These findings support the overarching hypothesis that MDD worsens with prefrontal disinhibition.

The aim of this study was to examine worsening of OCD symptoms after childbirth in individuals seeking assessment or treatment of OCD. The postpartum period may make parents biologically and psychologically vulnerable to OCD symptoms. Participants included 222 parents with OCD who completed surveys through a self-help website. Most women and almost half of men with self-reported OCD reported an increase in OCD symptoms following childbirth. Retrospective report of perceived worsening of OCD symptoms after childbirth was associated with more aggressive obsessions for both men and women, in comparison to individuals whose OCD symptoms did not worsen around childbirth. Women whose OCD symptoms worsened after childbirth reported more impairment in social functioning than individuals whose symptoms did not worsen. These results highlight the need to develop a better understanding of aggressive obsessions in parents, and improve education about prevalence, content, assessment, and intervention for aggression-focused intrusive thoughts.

Background: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory target., Methods: We tested this concept by attempting to retrospectively explain through predictive modeling the ranks of clinical improvement as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 10 patients with obsessive-compulsive disorder who underwent DBS to the ventral anterior limb of internal capsule with subsequent programming uninformed by the putative target tract., Results: Rank predictions were carried out using the tract model by a team that was completely uninvolved in DBS planning and programming. Predicted Y-BOCS improvement ranks significantly correlated with actual Y-BOCS improvement ranks at the 6-month follow-up (r = 0.75, p = .013). Predicted score improvements correlated with actual Y-BOCS score improvements (r = 0.72, p = .018)., Conclusions: Here, we provide data in a first-of-its-kind report suggesting that normative tractography-based modeling can blindly predict treatment response in DBS for obsessive-compulsive disorder., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12-30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit., (© 2024. The Author(s).)

Background: Deep brain stimulation (DBS) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum. However, the precise target within this region remains a matter of debate., Methods: Here, we retrospectively studied a multicenter cohort of 82 patients with OCD who underwent DBS of the ventral capsule/ventral striatum and mapped optimal stimulation sites in this region., Results: DBS sweet-spot mapping performed on a discovery set of 58 patients revealed 2 optimal stimulation sites associated with improvements on the Yale-Brown Obsessive Compulsive Scale, one in the anterior limb of the internal capsule that overlapped with a previously identified OCD-DBS response tract and one in the region of the inferior thalamic peduncle and bed nucleus of the stria terminalis. Critically, the nucleus accumbens proper and anterior commissure were associated with beneficial but suboptimal clinical improvements. Moreover, overlap with the resulting sweet- and sour-spots significantly estimated variance in outcomes in an independent cohort of 22 patients from 2 additional DBS centers. Finally, beyond obsessive-compulsive symptoms, stimulation of the anterior site was associated with optimal outcomes for both depression and anxiety, while the posterior site was only associated with improvements in depression., Conclusions: Our results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Obsessive-compulsive disorder (OCD) in children and adolescents is a neurobehavioral condition that can lead to functional impairment in multiple domains and decreased quality of life. We review the clinical presentation, diagnostic considerations, and common comorbidities of pediatric OCD. An overview of the biological and psychological models of OCD is provided along with a discussion of developmental considerations in youth. We also describe evidence-based treatments for OCD in childhood and adolescence, including cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) and pharmacotherapy. Finally, research evaluating the delivery of CBT in different formats and modalities is discussed, and we conclude with suggestions for future research directions.

In daily life, we must recognize others' emotions so we can respond appropriately. This ability may rely, at least in part, on neural responses similar to those associated with our own emotions. We hypothesized that the insula, a cortical region near the junction of the temporal, parietal, and frontal lobes, may play a key role in this process. We recorded local field potential (LFP) activity in human neurosurgical patients performing two tasks, one focused on identifying their own emotional response and one on identifying facial emotional responses in others. We found matching patterns of gamma- and high-gamma band activity for the two tasks in the insula. Three other regions (MTL, ACC, and OFC) clearly encoded both self- and other-emotions, but used orthogonal activity patterns to do so. These results support the hypothesis that the insula plays a particularly important role in mediating between experienced vs. observed emotions., Competing Interests: Declaration of interests SAS has consulting agreements with Boston Scientific, NeuroPace, Abbott, Zimmer Biomet, Varian Medical, and Sensoria Therapeutics and is co-founder of Motif. WKG has received donated devices from Medtronic and has consulting agreements with Biohaven Pharmaceuticals. SJM has served as a consultant or received research support from the following companies: Abbott, Almatica Pharma, Biohaven, BioXcel Therapeutics, Boehringer-Ingelheim, Brii Biosciences, Clexio Biosciences, COMPASS Pathways, Delix Therapeutics, Douglas Pharmaceuticals, Engrail Therapeutics, Freedom Biosciences, Liva Nova, Levo Therapeutics, Merck, Motif, Neumora, Neurocrine, Perception Neurosciences, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Seelos Therapeutics, Signant Health, Sunovion, Xenon Pharmaceuticals, Worldwide Clinical Trials, and XW Pharma. NP is a consultant for Abbott Laboratories and Sensoria Therapeutics. KRB has one patent awarded (US 11,241,575) and a second patent pending (US 63/592,453), which are not related to the findings of the current manuscript. The remaining authors declare no competing interests.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Background: Obsessive-compulsive disorder (OCD) and co-occurring posttraumatic stress disorder (PTSD) is associated with more severe and chronic OCD. However, findings regarding treatment effectiveness of cognitive behavioral treatment (CBT) with exposure and response prevention (ERP) with this comorbidity are mixed. Research aimed at understanding the precise barriers to OCD treatment effectiveness for individuals with co-occurring PTSD may help elucidate unique treatment needs., Methods: The current study used linear regression and latent growth curve analysis comparing treatment response and trajectory from patients with OCD (n = 3083, 94.2 %) and OCD + PTSD (n = 191, 5.2 %) who received CBT with ERP in two major intensive OCD treatment programs., Results: Although patients with OCD + PTSD evidenced similar trajectories of overall severity change, patients at one site required nearly 11 additional treatment days to achieve comparable reduction in OCD severity. Further, at the dimensional level, those with OCD + PTSD had poorer treatment response for unacceptable thoughts and symmetry symptoms. The moderate effect for unacceptable thoughts, indicating the widest gap in treatment response, suggests these symptoms may be particularly relevant to PTSD., Limitations: Findings are limited by a naturalistic treatment sample with variation in treatment provision., Conclusions: Findings emphasize caution in using a one-size-fits-all approach for patients with co-occurring OCD + PTSD within intensive OCD treatment programs, as broadly defined outcomes (e.g., reduction in overall severity) may not translate to reduction in the nuanced symptom dimensions likely to intersect with trauma. Unacceptable thoughts and symmetry symptoms, when co-occurring with PTSD, may require a trauma-focused treatment approach within intensive OCD treatment., Competing Interests: Declaration of competing interest Dr. Pinciotti reports receiving fees to be a consultant and workshop presenter with Jenna Overbaugh, LLC and The Knowledge Tree. Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He was formerly a consultant for Brainsway and Biohaven Pharmaceuticals in the past 12 months. He owns stock less than $5000 in NView and receives royalties for distribution of the YBOCS scales. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Dr. Goodman receives research funding from NIH, Biohaven, and the McNair Foundation and consulting fees from Biohaven. He receives royalties for distribution of the YBOCS scales. Dr. Cervin receives research support from the Swedish Research Council for Health, Working Life and Welfare, the Lindhaga Foundation, Stiftelsen Clas Grochinskys Minnesfond, the Crown Princess Lovisa's Association, Region Skåne, Fonden för Psykisk Hälsa, and Skåne University Hospital's Foundations and Donations; and financial compensation from Springer for editorial work outside of the submitted work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Family accommodation (e.g., reassurance, modifying routines, assisting avoidance) has not been explored among youth with misophonia but may have important clinical and intervention implications. We examined family accommodation in 102 children and adolescents with interview-confirmed misophonia and compared its frequency and content to family accommodation in 95 children and adolescents with anxiety disorders. Findings showed that family accommodation was ubiquitous in pediatric misophonia and may be even more frequent than in youth with anxiety disorders. Assisting the child, participating in misophonia-related behaviors, and modifying family routines were endorsed by more than 70% of parents of children with misophonia. Further, compared to parents of children with anxiety disorders, parents of children with misophonia more frequently reported child distress and anger when they did not accommodate. Family accommodation was moderately to strongly associated with misophonia severity even when accounting for co-occurring internalizing and externalizing symptoms and sociodemographic factors. This first study of family accommodation in pediatric misophonia suggests accommodation may be an important clinical feature. A notable study limitation is that the measure of misophonia did not delineate between adaptive versus maladaptive accommodations. Excessive and maladaptive accommodation may be one potential candidate to target in interventions when considered within a broader treatment plan. Importantly, adaptive accommodations should also be considered in day-to-day management if they improve functioning and quality of life., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders, though to date it has been minimally tested. In this study, 87 autistic youth (7 to 13 years old) with anxiety disorders and their parents were randomized to two forms of parent-led CBT in which parents led their child through a guided CBT workbook across 12 weeks: one with low therapist contact (four 30-minute telehealth calls), and one with standard therapist contact (ten 60-minute telehealth calls). Anxiety, functional impairment, and autism features significantly declined across therapy, without differences between groups. High satisfaction was reported in both groups, though significantly higher satisfaction ratings were reported in standard-contact CBT. Responder rates were 69% of completers at posttreatment (70% in standard contact, 68% in low contact) and 86% at 3-month follow-up (86% in standard contact, 87% in low contact). Low-contact CBT was estimated to incur an average cost of $755.70 per family compared with $1,978.34 in standard-contact CBT. Parent-led CBT with minimal or standard therapist contact both appear to be effective CBT delivery formats for autistic youth with anxiety disorders, with significant cost savings for low-contact CBT., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Purpose: Using data from a randomized clinical trial evaluating cognitive behavioral therapy (CBT) for children with autism and co-occurring anxiety, this study examined the relationship between autism features and anxiety symptoms throughout CBT., Methods: Two multilevel mediation analyses were run which examined the mediating role of changes in anxiety for changes in two core features of autism, (a) repetitive and restrictive behaviors (RRBs) and (b) social communication/interaction impairments, between pre- and post-treatment., Results: Indirect effects between time and autism characteristics were significant for both models, indicating that as anxiety changes, so do RRBs and social communication/interaction as the outcomes respectively., Conclusion: Findings suggest a bidirectional relationship between anxiety and autism features. Implications of these findings are discussed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) are recommended treatments for pediatric obsessive-compulsive disorder (OCD), but their relative efficacy and acceptability have not been comprehensively examined. Further, it remains unclear whether the efficacy of in-person CBT is conserved when delivered in other formats, such as over telephone/webcam or as Internet-delivered CBT (ICBT)., Methods: PubMed, PsycINFO, trial registries, and previous systematic reviews were searched for randomized controlled trials (RCTs) comparing CBT (in-person, webcam/telephone-delivered, or ICBT) or SRIs with control conditions or each other. Network meta-analyses were conducted to examine efficacy (post-treatment Children's Yale-Brown Obsessive Compulsive Scale) and acceptability (treatment discontinuation). Confidence in effect estimates was evaluated with CINeMA (Confidence in Network Meta-Analysis)., Results: Thirty eligible RCTs and 35 contrasts comprising 2,057 youth with OCD were identified. In-person CBT was significantly more efficacious than ICBT, waitlist, relaxation training, and pill placebo (MD range: 3.95-11.10; CINeMA estimate of confidence: moderate) but did not differ significantly from CBT delivered via webcam/telephone (MD: 0.85 [-2.51, 4.21]; moderate), SRIs (MD: 3.07 [-0.07, 6.20]; low), or the combination of in-person CBT and SRIs (MD: -1.20 [-5.29, 2.91]; low). SRIs were significantly more efficacious than pill placebo (MD: 4.59 [2.70, 6.48]; low) and waitlist (MD: 8.03 [4.24, 11.82]; moderate). No significant differences for acceptability emerged, but confidence in estimates was low., Conclusions: In-person CBT and SRIs produce clear benefits compared to waitlist and pill placebo and should be integral parts of the clinical management of pediatric OCD, with in-person CBT overall having a stronger evidence base. The combination of in-person CBT and SRIs may be most efficacious, but few studies hinder firm conclusions. The efficacy of CBT appears conserved when delivered via webcam/telephone, while more trials evaluating ICBT are needed., (© 2024 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objectives: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD., Materials and Methods: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs)., Results: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion., Conclusions: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD., Competing Interests: Conflict of Interest Tina Chou reports consulting fees from Kintsugi Mindful Wellness. Darin D. Dougherty reports research support and honoraria from Medtronic, an advisory role at Celanese, Sage, and Boehringer Ingelheim, and equity and an advisory role at Innercosmos, Intrinsic Powers, and Neurable. Wayne K. Goodman reports consulting fees from Biohaven, royalties from nView LLC and OCD scales, LLC, and funding from National Institutes of Health, The Robert and Janice McNair Foundation, and International Obsessive Compulsive Disorder Foundation. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Major depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth., Methods: A sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis., Results: Youth with MDD and OCD, compared to those with MDD and no OCD, had more severe MDD (Cohen's d = 0.39) and more reported moderate to severe depression (75 % vs 61 %). When accounting for demographic variables and the overall severity of MDD, those with comorbid OCD reported lower levels of anhedonia and more severe difficulties with psychomotor retardation/agitation. No significant differences in the interconnections among symptoms emerged., Limitations: Data were cross-sectional and self-reported, gold standard diagnostic tools were not used to assess OCD, and the sample size for the group with MDD and OCD was relatively small yielding low statistical power for network analysis., Conclusions: Youth with MDD and OCD have more severe MDD than those with MDD and no OCD and they experience more psychomotor issues and less anhedonia, which may relate to the behavioral activation characteristic of OCD., Competing Interests: Declaration of competing interest Ms. Strouphauer, Mr. Valenzuela-Florez, Mr. Elmore, and Drs. Minhajuddin, Slater, Riddle, Guzick, Hettema, Wakefield, Pinciotti, Tonarelli, and Gushanas do not have any conflicts to declare. Dr. Soutullo reports for the period 2018–2022 non-personal research funds from Lundbeck and Janssen; is a consultant/advisory board member of Editorial Médica Panamericana, EUNETHYDIS (European Network on Hyperkinetic Disorder), NeuroTech Solutions Ltd. (Israel), Limbix Health DSMB (United States), MEDEA (Spain), Tech Innosphere Engineering LTD (Germany), and Shire/now part of Takeda (Spain); received speaker's bureau fees from Bial (Portugal), Cuquerella Medical Consulting (Spain), Medice (Germany), Rubio (Spain), Tecnofarma (Peru), and Shire/now part of Takeda (Spain), and royalties from Editorial Médica Panamericana (Spain). Dr. Goodman receives research fundings from NIH, Biohaven, and the McNair Foundation, royalties from Proem related to the licensing of the YBOCS scales, and consulting fee from Biohaven. Dr. Trivedi has provided consulting services to Acadia Pharmaceuticals, Alkermes Inc., Alto Neuroscience Inc, Axsome Therapeutics, Biogen MA Inc, Cerebral Inc., Circular Genomics Inc., Compass Pathfinder Limited, GH Research, GreenLight VitalSign6 Inc, Heading Health, Janssen Pharmaceutical, Legion Health, Merck Sharp & Dohme Corp., Mind Medicine Inc., Myriad Neuroscience, Naki Health Ltd, Navitor, Neurocrine Biosciences Inc., Noema Pharma AG, Orexo US Inc., Otsuka America Pharmaceutical Inc, Perception Neuroscience Holdings, Pharmerit International, Policy Analysis Inc., Praxis Precision Medicines Inc, PureTech LYT Inc, Relmada Therapeutics Inc., Rexahn Pharmaceuticals, Inc., SAGE Therapeutics, Signant Health, Sparian Biosciences, Titan Pharmaceuticals, Takeda Pharmaceuticals Inc, WebMD. He has received grant/research funding from NIMH, NIDA, NCATS, American Foundation for Suicide Prevention, Patient-Centered Outcomes Research Institute (PCORI), and Blue Cross Blue Shield of Texas. Additionally, he has received editorial compensation from Engage Health Media, and Oxford University Press. Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He was formerly a consultant for Brainsway and Biohaven Pharmaceuticals in the past 12 months. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley Dr. Cervin receives research support from the Swedish Research Council for Health, Working Life and Welfare, the Lindhaga Foundation, Stiftelsen Clas Grochinskys Minnesfond, the Crown Princess Lovisa's Association, Region Skåne, Fonden för Psykisk Hälsa, and Skåne University Hospital's Foundations and Donations; and financial compensation from Springer for editorial work outside of the submitted work., (Copyright © 2024. Published by Elsevier B.V.)

Background: Misophonia is a complex condition characterized by extreme emotional distress in response to specific sounds or specific visual stimuli. Despite a growing body of clinical and neuroscientific literature, the etiology of this condition remains unclear. Hyperarousal, that is, a state of heightened alertness and disinhibition, as a core feature of misophonia is supported by behavioral and neuroimaging literature and might represent a viable clinical target for the development of both behavioral and pharmacological interventions. The aim of this study was to investigate how hyperarousal might be linked to neurocognitive processes associated with vigilance and stimulus discrimination in youth with misophonia., Methods: We compared 72 children and adolescents with misophonia (13.74 ± 2.44 years) (64 % female) and 89 children and adolescents with anxiety (12.35 ± 2.57 years) (58.4 % female) on behavioral and signal detection performance of the immediate memory task (IMT). Anxiety patients were used as a clinical control group to distinguish attentional processes specific for misophonia., Results: Both groups demonstrated similar behavioral performance, including response rate and reaction time. However, misophonia was associated with elevated stimulus discrimination (d prime), which in turn was positively correlated with the severity of misophonia trigger reports., Conclusions: Our findings are in line with previous cognitive and neuroimaging studies, and support an arousal-based model of misophonia, where individuals with misophonia experience a state of heightened vigilance, being more aware of stimuli in the environment. Our findings provide a neurocognitive basis for future study of neurochemical imaging that might further progress towards clinical targets., Competing Interests: Declaration of competing interest N. Murphy has received grants/research support from NIMH (1R21MH119441-01A1); REAM Misophonia Research Fund (The REAM Foundation - YR01); Caroline Wiess Law Fund for Research in Molecular Medicine, and has previously received research support as a subinvestigator for clinical research for Neurocrine Biosciences Inc. M. Cervin receives research support from the Swedish Research Council for Health, Working Life and Welfare, the Lindhaga Foundation, Stiftelsen Clas Grochinskys Minnesfond, the Crown Princess Lovisa's Association, Region Skåne, and Skåne University Hospital's Foundations and Donations; and financial compensation from Springer for editorial work outside of the submitted work. Dr. Guzick receives grant support from the REAM Foundation/Misophonia Research Fund as well as the Texas Higher Education Coordinating Board. Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView (for distribution of the Y-BOCS and CY-BOCS) and Limbix. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To examine the efficacy of the parent-led intervention Supportive Parenting for Anxious Childhood Emotions (SPACE) relative to a low-dose version of the protocol among children and adolescents with clinically significant anxiety and/or obsessive-compulsive disorder (OCD)., Method: 68 youth (7-17) with anxiety/OCD and their parents were randomized to receive 12 weekly telehealth SPACE sessions (SPACE-Standard) or bibliotherapy plus 4 telehealth sessions over 12 weeks (SPACE-light). After screening, assessments were conducted via videoconferencing at baseline, post-treatment, and one-month follow-up. Independent evaluators were blind to treatment condition., Results: Treatment condition did not predict whether a participant responded to the intervention (SPACE-Standard = 70%; SPACE-Light = 68%), nor was treatment condition a predictor of anxiety severity, parent-reported anxiety, or parent-/child-reported functional impairment at post-treatment or one-month follow-up. Youth in SPACE-Light self-reported higher post-treatment anxiety than youth in SPACE-standard, though this was no longer significant at one-month follow-up. Parent-reported family accommodation total change scores were associated with anxiety severity at post-treatment across both arms., Conclusion: This is the second randomized controlled trial (RCT) evaluating SPACE and provides further support for the efficacy of this intervention both in standard and low-dose formats. This study provides support for parent-led anxiety treatment targeting family accommodation as a primary mechanism of change and extends evidence of efficacy to a more clinically diverse sample., Trial Registration: ClinicalTrials.gov Registry: NCT04922502.https://classic., Clinicaltrials: gov/ct2/show/NCT04922502., Competing Interests: Declaration of competing interest Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Ms. Ayton, Dr. Guzikck, Dr. Palo, Ms. Kook, Dr. Candelari, Ms. Maye, Dr. McNeel, Ms. Trent, Ms. Garcia, Dr. Onyeka, and Ms Rast have no disclosures to report. Dr. Shimshoni receives royalties from books (including on SPACE, the treatment examined in this study) and revenue from clinical training workshops. Dr. Lebowitz receives royalties from books (including on SPACE, the treatment examined in this study) and revenue from clinical training workshops. Dr. Goodman receives research fundings from NIH, Biohaven, and the McNair Foundation and consulting fee from Biohaven. He receives royalties from Proem., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prefrontal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders. However, the detailed neurophysiological effects of stimulation to these hubs are largely unknown. Here, we performed intracranial recordings across prefrontal networks while delivering electrical stimulation to two well-established white matter hubs involved in cognitive regulation and depression: the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS). We demonstrate a shared frontotemporal circuit consisting of the ventromedial prefrontal cortex, amygdala, and lateral orbitofrontal cortex where gamma oscillations are differentially modulated by stimulation target. Additionally, we found participant-specific responses to stimulation in the dorsal anterior cingulate cortex and demonstrate the capacity for further tuning of neural activity using current-steered stimulation. Our findings indicate a potential neurophysiological mechanism for the dissociable therapeutic effects seen across the SCC and VC/VS targets for psychiatric neuromodulation and our results lay the groundwork for personalized, network-guided neurostimulation therapy., Competing Interests: SS has consulting agreements with Boston Scientific, Neuropace, Abbott, and Zimmer Biomet, Varian Medical and Sensoria Therapeutics and is a co-founder for Motif Neurotech. NP was a consultant for Second Sight Medical Products, Abbott Laboratories, Boston Scientific, and Sensoria Therapeutics. WG has received donated devices from Medtronic, has consulted for Biohaven Pharmaceuticals and receives royalties from Nview, LLC. SM was supported through the use of resources and facilities at the Michael E. Debakey VA Medical Center, Houston, Texas and receives support from The Menninger Clinic. SM has served as a consultant to Allergan, Alkermes, Axsome Therapeutics, BioXcel Therapeutics, Clexio Biosciences, COMPASS Pathways, Eleusis, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Praxis Precision Medicines, Neumora, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Seelos Therapeutics, and Sunovion. He has received research support from Biohaven Pharmaceuticals, Boehringer-Ingelheim, Janssen, Merck, Sage Therapeutics, and VistaGen Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Allawala, Bijanki, Oswalt, Mathura, Adkinson, Pirtle, Shofty, Robinson, Harrison, Mathew, Goodman, Pouratian, Sheth and Borton.)

Background: Evidence suggests that depressive symptoms tend to improve concurrently with obsessive-compulsive disorder (OCD) symptoms during cognitive behavioral therapy (CBT), despite depression not being the primary target of intervention. Studies examining the temporal or mediational relationships of OCD and depressive symptoms have indicated a bidirectional relationship, as prior levels of OCD symptoms influenced subsequent levels of depression, and vice versa. Deep transcranial magnetic stimulation (dTMS) has recently emerged as a treatment option for OCD. Whether dTMS affects depression symptoms similarly to CBT remains to be examined., Methods: The current study employed a random intercept cross-lagged panel model (RI-CLPM) to examine the relationship of OCD and depression symptoms in 94 treatment refractory patients, undergoing dTMS or sham treatment., Results: Both OCD and depression symptoms improved significantly. However, a stable, cross-lagged relationship between the variables was not supported. Changes in one symptom domain could not be used to predict the other., Limitations: The present study was conducted in a treatment refractory population, meaning the present findings may not generalize to treatment naïve patients or those with less severe OCD symptoms. It is unclear whether the study was sufficiently powered to detect the effects of interest, and this concern also meant that examining the dTMS and sham groups independently was not feasible., Conclusions: When treating OCD with dTMS, depression symptoms appear likely to diminish but should be monitored throughout, and additional interventions applied if needed., Competing Interests: Declaration of competing interest Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He was a consultant for Brainsway and Biohaven Pharmaceuticals in the past 12 months. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Dr. Guzick reports research funding from the Ream Foundation. Aron Tendler is a consultant chief medical officer for BrainsWay, the manufacturers of Deep TMS, and has a financial interest in BrainsWay, Alpha Tau Medical and a commercial TMS center. HE has received research support in the last twelve months from Liva Nova, Biohaven and BrainsWay. The other authors have no disclosures. The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This trial examined stepped-care cognitive-behavioral treatment (CBT) among 96 autistic youth with co-occurring anxiety. Step 1 included an open trial of parent-led, therapist-guided bibliotherapy. Step 2 was family-based CBT for those who did not respond to Step 1 or maintenance for those who did. Eighteen participants (28%) who completed Step 1 responded. Responders reported significantly lower pre-treatment anxiety, internalizing symptoms, and functional impairment than non-responders. After Steps 1 and 2, 80% of completers (55% intent-to-treat) were responders. Anxiety, impairment, and ASD-related impairments significantly improved. Youth in maintenance experienced faster improvement through post-treatment, though there were no group differences at 3-month-follow-up. A stepped approach may help some individuals in Step 1, particularly those who are less anxious., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Computer-assisted cognitive behavioral therapy (CCBT) for childhood anxiety disorders may aid the dissemination of CBT, while maintaining treatment fidelity. Although CCBT is an effective intervention, not everyone benefits equally from treatment. Identifying patient characteristics that predict who will benefit from treatment and to what extent can help with matching patients to suitable interventions, and allow researchers and clinicians to modify, and individualize, their treatment formats more effectively. Such predictors and moderators have not yet been examined for CCBT outcomes in anxious children and studies of more traditional treatment formats have yielded inconsistent results. Methods: Using data from a randomized clinical trial evaluating CCBT for children with anxiety disorders, this study examined predictors and moderators of treatment outcomes in a sample of 100 children (age: mean [ M ] = 9.82, standard deviation [ SD ] = 1.82), randomized to either CCBT ( n  = 49) or standard community care ( n  = 51). Potential predictors and moderators were identified from the literature and examined in stepwise multiple linear regression models, using posttreatment anxiety severity and global impairment as outcomes. Results: Parent-rated internalizing symptoms predicted posttreatment anxiety severity for both treatment groups. High pretreatment levels of anxiety severity predicted higher global impairment at posttreatment for the group receiving community care, but not for the CCBT group. Conclusion: Further research is needed to clarify which patient characteristics are associated with CCBT outcomes in a consistent way. ClinicalTrials.gov identifier: NCT01416805.

Background: Misophonia is characterized by intense emotional reactions to specific sounds or visual stimuli and typically onsets during childhood. An obstacle for research and clinical practice is that no comprehensively evaluated measures for pediatric misophonia exist., Methods: In a sample of 102 youth meeting the proposed diagnostic criteria of misophonia, we evaluated the child and parent-proxy versions of the self-reported Misophonia Assessment Questionnaire (MAQ; assessing broad aspects of misophonia) and the child version of the Amsterdam Misophonia Scale (A-MISO-S; assessing misophonia severity). Confirmatory and exploratory factor analysis were used to examine factor structures of the measures. Further, child-parent agreement on the MAQ and associations between both measures and misophonia-related impairment, quality of life, and misophonia-related school interference were examined to evaluate aspects of convergent validity., Results: For both youth- and parent-ratings, four MAQ factors emerged: pessimism, distress, interference, and non-recognition. A-MISO-S showed a unidimensional structure, but the item 'effort to resist' did not load significantly onto the unidimensional factor. Good child-parent agreement on the MAQ scales were found and both MAQ and A-MISO-S were moderately to strongly associated with misophonia-related impairment, quality of life (inverse association), and misophonia-related school interference., Limitations: MAQ and A-MISO-S assess sensitivity to auditory but not visual stimuli, the sample size was modest, and repeated assessments were not conducted., Conclusions: The combination of MAQ and A-MISO-S shows promise as a multidimensional assessment approach for pediatric misophonia. Future evaluations should include known-groups validity, screening performance, and sensitivity to change in symptom severity., Competing Interests: Declaration of competing interest None, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis., Methods: We recorded high-density neural activity from intracranial electrodes implanted in depression-relevant prefrontal cortical regions in 3 human subjects with severe depression. Neural recordings were labeled with depression severity scores across a wide dynamic range using an adaptive assessment that allowed sampling with a temporal frequency greater than that possible with typical rating scales. We modeled these data using regularized regression techniques with region selection to decode depression severity from the prefrontal recordings., Results: Across prefrontal regions, we found that reduced depression severity is associated with decreased low-frequency neural activity and increased high-frequency activity. When constraining our model to decode using a single region, spectral changes in the anterior cingulate cortex best predicted depression severity in all 3 subjects. Relaxing this constraint revealed unique, individual-specific sets of spatiospectral features predictive of symptom severity, reflecting the heterogeneous nature of depression., Conclusions: The ability to decode depression severity from neural activity increases our fundamental understanding of how depression manifests in the human brain and provides a target neural signature for personalized neuromodulation therapies., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Autistic youth often present with comorbid anxiety and depression yet there is a dearth of validated assessment tools. The Revised Children's Anxiety and Depression Scale (RCADS) assesses internalizing symptoms but there is little psychometric data in autistic youth. Treatment-seeking autistic youth with anxiety or obsessive-compulsive symptoms ( N = 74; age 6-14 years), and caregivers, were administered the RCADS-Parent, RCADS-Child, and assessments of internalizing, externalizing symptoms and social impairment indicative of autism. RCADS-Parent and RCADS-Child total anxiety scores demonstrated excellent internal consistency, and the six subscales demonstrated acceptable-to-good internal consistency. The RCADS-Child and Parent total anxiety scores were weakly correlated, and neither child age nor gender altered the strength of this association. Convergent validity was supported by moderate-to-strong correlations with clinician and parent-reported anxiety symptoms. Support for divergent validity was mixed. Results provide support for the RCADS-Parent and RCADS-Child as reliable, valid measures of internalizing symptoms in autistic youth.

Obsessive-compulsive disorder is an impairing psychiatric condition affecting 1-2% of adults and youth. Cognitive-behavioral therapy with exposure and response prevention (CBT) is an efficacious intervention but requires specialty training and access is often limited. While certain factors are associated with treatment access, one key barrier that has not been explored is the geographic availability of OCD treatment providers. Using integrated geographically-referenced data, we examined the geographic distribution of OCD CBT specialty providers across the state of Texas, with particular attention to the relationship to neighborhood socioeconomic disadvantage, insurance status, and rural versus urban status. We found that specialist providers are almost exclusively located inside the highly urbanized parts of the state, primarily in more affluent areas, and often only accept self-pay. The characteristics of the areas located the furthest away from specialty OCD care include a high proportion of persons identifying as Hispanic; a high proportion of non-English speakers, households with income below poverty; households with no vehicles; and persons with no health insurance. Average household income decreased as distances from specialist providers increased. Broadly, findings confirm that OCD CBT specialty providers are clustered in large socially advantaged areas and that economic disadvantage remains a significant barrier to care. As inadequate or inappropriate treatment of OCD is likely to result in sustained and impairing symptoms, this is of great concern.

Obsessive-compulsive disorder (OCD), anxiety disorders, and depressive disorders are highly comorbid, and each contribute to significant functional impairment for affected youth. Comorbid anxiety disorders in depressed youth have been associated with greater depressive symptom severity and impairment, but the impact of comorbid OCD in this population remains unclear. Accordingly, the present study examined the differential clinical characteristics of youth with depression and comorbid OCD relative to age/gender matched depressed youth with no such comorbidity and to those with depression and a comorbid (non-OCD) anxiety disorder. A sample of 797 youth and young adults ages 8-20 years who met diagnostic criteria for depression alone, depression with co-occurring OCD or any anxiety disorder were included in the present study. Rates of comorbid anxiety and OCD were very high (60.5% and 15.5%, respectively). Relative to youth with only depression, depressed youth with comorbid OCD or anxiety had greater severity of depression, suicidality, and overall impairment in social, physical, and emotional functioning. These results highlight the contribution of OCD or anxiety comorbidity in more complex clinical presentations for depressed youth., Competing Interests: Declarations Dr. Trivedi is or has been an advisor/consultant and received fees from Acadia Pharmaceuticals, Inc., Alkermes Inc, Axsome Therapeutics, Biogen MA Inc., Circular Genomics Inc., GH Research Limited, Heading Health Inc., Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc., Neurocrine Biosciences Inc, Noema Pharma AG, Orexo US Inc, Otsuka American Pharmaceutical Inc., Otsuka Canada Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc., SAGE Therapeutics, Takeda Pharmaceutical Company Ltd., and Titan Pharmaceuticals Inc. Dr. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He is a consultant for Brainsway and Biohaven Pharmaceuticals. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Dr. Storch is an Editorial Board Member. Given their role as an Editorial Board Member, Dr. Storch had no involvement in the peer-review of this article and had no access to information regarding its peer-review. Drs. Riddle, Guzick, Minhajuddin, Slater, Baughn, Martin, Wakefield, and Goodman do not have conflicts to declare. Mr. Smárason, Ms. Armstrong and Mayes do not have conflicts to declare.

Neural recordings frequently get contaminated by ECG or pulsation artifacts. These large amplitude components can mask the neural patterns of interest and make the visual inspection process difficult. The current study describes a sparse signal representation strategy that targets to denoise pulsation artifacts in local field potentials (LFPs) recorded intraoperatively. To estimate the morphology of the artifact, we first detect the QRS-peaks from the simultaneously recorded ECG trace as an anchor point. After the LFP data has been epoched with respect to each beat, a pool of raw data segments of a specific length is generated. Using the K-singular value decomposition (K-SVD) algorithm, we constructed a data-specific dictionary to represent each contaminated LFP epoch in a sparse fashion. Since LFP is aligned to each QRS complex and the background neural activity is uncorrelated to the anchor points, we assumed that constructed dictionary will be formed to mainly represent the pulsation artifact. In this scheme, we performed an orthogonal matching pursuit to represent each LFP epoch as a linear combination of the dictionary atoms. The denoised LFP data is thus obtained by calculating the residual between the raw LFP and its approximation. We discuss and demonstrate the improvements in denoised data and compare the results with respect to principal component analysis (PCA). We noted that there is a comparable change in the signal for visual inspection to observe various oscillating patterns in the alpha and beta bands. We also see a noticeable compression of signal strength in the lower frequency band (<13 Hz), which was masked by the pulsation artifact, and a strong increase in the signal-to-noise ratio (SNR) in the denoised data.Clinical Relevance- Pulsation artifact can mask relevant neural activity patterns and make their visual inspection difficult. Using sparse signal representation, we established a new approach to reconstruct the quasiperiodic pulsation template and computed the residue signal to achieve noise-free neural activity.

Research into misophonia treatments has been limited and it is unclear what treatment approaches may be effective. This systematic review extracted and synthesized relevant treatment research on misophonia to examine the efficacy of various intervention modalities and identify current trends in order to guide future treatment research. PubMed, PsycINFO, Google Scholar, and Cochrane Central were searched 4using the keywords "misophonia," "decreased sound tolerance," "selective sound sensitivity," or "decreased sound sensitivity." Of the 169 records available for initial screening, 33 studied misophonia treatment specifically. Data were available for one randomized controlled trial, one open label trial, and 31 case studies. Treatments included various forms of psychotherapy, medication, and combinations of the two. Cognitive-behavioral therapy (CBT) incorporating various components has been the most often utilized and effective treatment for reduction of misophonia symptoms in one randomized trial and several case studies/series. Beyond CBT, various case studies suggested possible benefit from other treatment approaches depending on the patient's symptom profile, although methodological rigor was limited. Given the limitations in the literature to date, including overall lack of rigor, lack of comparative studies, limited replication, and small sample size, the field would benefit from the development of mechanism-informed treatments, rigorous randomized trials, and treatment development with an eye towards dissemination and implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Obsessive-compulsive disorder (OCD) affects 1-2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI + CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address this gap through a two phase, double-blinded, placebo-controlled, randomized controlled non-inferiority trial with the purpose of evaluating whether youth with OCD on an SRI can discontinue their medication after successful CBT augmentation and maintain wellness for a period of 24 weeks during which they receive maintenance CBT that models standard-of-care. In this paper we describe the rationale and methodological design of the POWER study., Competing Interests: Declaration of competing interest We thank Sabine Wilhelm, Martin Franklin, and Judy Mac for their contributions to this project.