Remote Intensive Group Behavioral Treatment for Families of Children with Selective Mutism.

Selective mutism (SM) is a relatively rare, but highly interfering, child anxiety disorder characterized by a consistent failure to speak in certain situations, despite demonstrating fluent speech in other contexts. Exposure-based cognitive behavioral therapy and Parent-Child Interaction Therapy adapted for SM can be effective, but the broad availability and accessibility of such specialty care options remains limited. Stay-at-home guidelines to mitigate the spread of COVID-19 further limited the accessibility of office-based specialty care for SM. Building on separate lines of research supporting intensive treatments and telehealth service delivery models, this paper is the first to describe the development, preliminary feasibility, acceptability, and efficacy of a Remote Intensive Group Behavioral Treatment (IGBT) for families of young children with SM (N=9). Treatment leveraged videoconferencing technology to deliver caregiver training sessions, lead-in sessions, 5 consecutive daily IGBT sessions, and an individualized caregiver coaching session. Remote IGBT was found to be both feasible and acceptable. All families (100%) completed diagnostic assessments and caregiver-report questionnaires at four major study timepoints (i.e., intake, pre-treatment, post-treatment, 4-month follow-up) and participated in all treatment components. Caregivers reported high treatment satisfaction at post-treatment and 4-month follow-up and low levels of burden associated with treatment participation at post-treatment. Approximately half of participating children were classified as treatment responders by independent evaluators at post-treatment and 4-month follow-up. Although these pilot results should be interpreted with caution, the present work underscores the potential utility of using videoconferencing to remotely deliver IGBT to families in their natural environments.

Monitoring live mitochondrial metabolism in real-time using NMR spectroscopy.

Investigation of mitochondrial metabolism is gaining increased interest owing to the growing recognition of the role of mitochondria in health and numerous diseases. Studies of isolated mitochondria promise novel insights into the metabolism devoid of confounding effects from other cellular organelles such as cytoplasm. This study describes the isolation of mitochondria from mouse skeletal myoblast cells (C2C12) and the investigation of live mitochondrial metabolism in real-time using isotope tracer-based NMR spectroscopy. [3-13 C1 ]pyruvate was used as the substrate to monitor the dynamic changes of the downstream metabolites in mitochondria. The results demonstrate an intriguing phenomenon, in which lactate is produced from pyruvate inside the mitochondria and the results were confirmed by treating mitochondria with an inhibitor of mitochondrial pyruvate carrier (UK5099). Lactate is associated with health and numerous diseases including cancer and, to date, it is known to occur only in the cytoplasm. The insight that lactate is also produced inside mitochondria opens avenues for exploring new pathways of lactate metabolism. Further, experiments performed using inhibitors of the mitochondrial respiratory chain, FCCP and rotenone, show that [2-13 C1 ]acetyl coenzyme A, which is produced from [3-13 C1 ]pyruvate and acts as a primary substrate for the tricarboxylic acid cycle in mitochondria, exhibits a remarkable sensitivity to the inhibitors. These results offer a direct approach to visualize mitochondrial respiration through altered levels of the associated metabolites.

Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder.

Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. LAY SUMMARY: Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment.

In vitro characterization of immune modulating drug-eluting immunobeads towards transarterial embolization in cancer.

Hepatocellular carcinoma (HCC) is an aggressive liver cancer with limited effective treatment options. In this study, we selected TLR agonists imiquimod (IMQ), gardiquimod (GARD), GS-9620 and DSR 6434, and a small molecule checkpoint inhibitor, BMS-202, for characterization of drug loading and release from radiopaque embolic beads (DC Bead LUMI) for potential use in image-guided transarterial embolization (TACE) of HCC. The maximum drug loading capacity and amount of drug released over time were determined by high performance liquid chromatography and compared with the commonly used anthracycline, doxorubicin hydrochloride (Dox). Maximum drug loading was 204.54 ± 3.87, 65.28 ± 3.09, 65.95 ± 6.96, 65.97 ± 1.54, and 148.05 ± 2.24 mg of drug per milliliter of DC Bead LUMI for Dox, GARD, DSR 6434, IMQ, and BMS-202, respectively. Fast loading and subsequent rapid release in saline were observed for IMQ, GARD, and DSR 6434. These drugs could also be partially removed from the beads by repeated washing with de-ionized water suggesting weak interaction with the beads. Aggregation of IMQ was observed in water and saline. GS-9620 partially decomposed in the solubilizing solution, so loading and release were not characterized. Compared to TLR agonists, slower loading and release were observed for Dox and BMS-202. Potential factors influencing drug loading into and release from DC Bead LUMI including steric hinderance, hydrophobicity, drug pKa, and the electrostatic nature of the beads are discussed. The maximum loading capacity of BMS-202 and Dox in DC Bead LUMI exceeded the maximum theoretical loading capacity of the beads expected from ionic interaction alone suggesting additional drug-bead or drug-drug interactions may play a role. Slightly more release was observed for BMS-202 at early time points followed by a slower release compared to Dox. Further study of these drug-bead combinations is warranted in search of new tools for locoregional delivery of immune-modulating agents for treatment of HCC via drug-eluting bead chemoembolization.

Harnessing Home-School Partnerships and School Consultation to Support Youth With Anxiety.

Youth with anxiety often experience significant impairment in the school setting. Despite the relevance and promise of addressing anxiety in schools, traditional treatment approaches to school-based anxiety often do not adequately address generalization to the school setting, or they require removing the student from the classroom to deliver time- and staff-intensive programs. Such programs often leave teachers and caregivers feeling ill-equipped to support the student with anxiety throughout the natural course of the school day. Given the heavy demands placed on teachers and documented burnout among school professionals, providing effective school supports requires collaborative partnerships among outpatient therapists/specialists, school personnel, and caregivers. Drawing from literature on collaborative models for externalizing problems, we offer recommendations for outpatient therapists and specialists working to implement evidence-based supports in school settings and promote home-school partnerships to benefit youth with anxiety in the school setting. Our recommendations touch upon several components of such school consultation, including (a) identification of key parties involved, (b) conducting a needs assessment, (c) collaborative goal setting and development of a fear hierarchy, (d) plan development and implementation (e.g., facilitating a school-based exposure mindset, promoting home-school communication, enhancing school relationships), and (e) progress monitoring and ongoing support. We conclude with a case example to bring these recommendations to life.

Evaluation of immune-modulating drugs for use in drug-eluting microsphere transarterial embolization.

Cancer immunotherapy has yet to reach its full potential due in part to limited response rates and side effects inherent to systemic delivery of immune-modulating drugs. Local administration of immunotherapy using drug-eluting embolic (DEE) microspheres as drug delivery vehicles for direct infusion into tumor-feeding arteries might increase and prolong tumor drug concentrations and reduce systemic drug exposure, potentially improving the risk-to-benefit ratio of these agents. The purpose of this study was to evaluate the ability of four immune modulators affecting two different immune pathways to potentiate replication of immune cells from a woodchuck model of hepatocellular carcinoma. DSR 6434, a Toll-like receptor agonist, and BMS-202, a PD-L1 checkpoint inhibitor, induced immune cell replication and were successfully loaded into radiopaque DEE microspheres in high concentrations. Release of DSR 6434 from the DEE microspheres was rapid (t99% = 0.4 h) upon submersion in a physiologic saline solution while BMS-202 demonstrated a more sustained release profile (t99% = 17.9 h). These findings demonstrate the feasibility of controlled delivery of immune-modulating drugs via a local DEE microsphere delivery paradigm.

Transitioning to Telehealth Services in a Pediatric Diabetes Clinic During COVID-19: An Interdisciplinary Quality Improvement Initiative.

COVID-19 necessitated a rapid shift to telehealth for psychologists offering consultation-liaison services in pediatric medical settings. However, little is known about how psychologists providing these services adapted to using telehealth service delivery formats. This report details how our interdisciplinary team identified declining psychosocial screener completion and psychology consultation rates as primary challenges following a shift to telehealth within a pediatric diabetes clinic. We utilized the Plan-Do-Study-Act (PDSA) quality improvement framework to improve screening and consultation rates, which initially declined during the telehealth transition. Screening and consultation rates dropped initially, but recovered to nearly pre-pandemic levels following three PDSA intervention cycles. During implementation, challenges arose related to the feasibility of patient interactions, interdisciplinary collaboration, patient engagement, and ethical issues. Clinics shifting psychology consultation-liaison services to telehealth should prioritize interdisciplinary communication, elicit perspectives from all clinic professionals, leverage the electronic health record, and develop procedures for warm handoffs and navigating ethical issues.

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Therapist-Led, Internet-Delivered Treatment for Early Child Social Anxiety: A Waitlist-Controlled Evaluation of the iCALM Telehealth Program.

Despite recent advances in the treatment of early child social anxiety, the broad accessibility of brick-and-mortar services has been limited by traditional barriers to care, and more recently by new obstacles related to efforts to slow the spread of COVID-19. The present waitlist-controlled trial examined the preliminary efficacy of a family-based behavioral parenting intervention (i.e., the iCALM Telehealth Program) that draws on Parent-Child Interaction Therapy and videoconferencing to remotely deliver clinician-led care for anxiety in early childhood. Young children (3-8 years) with a diagnosis of social anxiety disorder (N = 40; 65% from ethnic/racial minority backgrounds) were randomly assigned to iCALM or waitlist. Intent-to-treat analyses found that at post, independent evaluators classified roughly half of the iCALM-treated children, but only 6% of waitlist children, as "Responders" (Wald test = 4.51; p = .03). By Post, iCALM led to significantly greater reductions than waitlist in child anxiety symptoms, fear, discomfort, and anxiety-related social impairment, and also led to greater improvements in child soothability. By 6-month follow-up, the percentage of iCALM-treated children classified as "Responders" rose to roughly 60%. Exploratory moderation tests found iCALM was particularly effective in reducing life impairments and parental distress among families presenting with higher, relative to lower, levels of baseline parental accommodation. The present findings add to a growing body of research supporting the promise of technology-based strategies for broadening the portfolio of options for delivering clinician-led mental health services.

Evaluation of Fumaric Acid and Maleic Acid as Internal Standards for NMR Analysis of Protein Precipitated Plasma, Serum, and Whole Blood.

Significant advances have been made in unknown metabolite identification and expansion of the number of quantifiable metabolites in human plasma, serum, and whole blood using NMR spectroscopy. However, reliable quantitation of metabolites is still a challenge. A major bottleneck is the lack of a suitable internal standard that does not interact with the complex blood sample matrix and also does not overlap with metabolite peaks apart from exhibiting other favorable characteristics. With the goal of addressing this challenge, a comprehensive investigation of fumaric and maleic acids as potential internal standards was made along with a comparison with the conventional standards, TSP (trimethylsilylpropionic acid) and DSS (trimethylsilylpropanesulfonic acid). Both fumaric acid and maleic acid exhibited a surprisingly high performance with a quantitation error <1%, while the TSP and DSS caused an average error of up to 35% in plasma, serum, and whole blood. Further, the results indicate that while fumaric acid is a robust standard for all three biospecimens, maleic acid is suitable for only plasma and serum. Maleic acid is not suited for the analysis of whole blood due to its overlap with coenzyme peaks. These findings provide new opportunities for improved and accurate quantitation of metabolites in human plasma, serum, and whole blood using NMR spectroscopy. Moreover, the use of protein precipitation prior to NMR analysis mirrors the sample preparation commonly used for mass spectrometry based metabolomics, such that these findings further strengthen efforts to combine and compare NMR and MS based metabolite data of human plasma, serum, and whole blood for metabolomics based research.

Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial.

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20-45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

Psychosocial Interventions for Attention-Deficit/Hyperactivity Disorder: Systematic Review with Evidence and Gap Maps.

OBJECTIVE: To inform the scope of future systematic reviews, meta-analyses, and treatment outcome studies, this review aims to describe the extent of the evidence for psychosocial interventions for children and adolescents with attention-deficit/hyperactivity disorder, with particular attention to specific types of interventions, targets of outcome assessment, and risk of bias. METHOD: A comprehensive search of relevant databases (i.e., Medline, PsychInfo, Education Resources Information Center, and ProQuest Dissertation Database) was conducted. Detailed information related to treatment type, outcome assessment, study design, and risk of bias was extracted by trained coders. Evidence and gap maps were created to summarize evidence within types of treatments and targets of outcome assessment. Indicators of risk of bias were assessed for selected combinations of treatments and outcome assessment. RESULTS: We identified 185 eligible individual studies and 3817 effect sizes. Behavioral parent training and cognitive training (COG) were the most commonly studied stand-alone interventions. Treatment versus control comparisons for stand-alone interventions (s = 70) were less common than for complex interventions involving combinations of psychosocial interventions (s = 100). Combinations of behavioral and child training (e.g., COG, organizational training) interventions were the most frequently studied. CONCLUSION: There is a considerable variability within this literature regarding combinations of treatments across outcome assessment targets. To address gaps in existing evidence, more primary studies assessing direct comparisons of isolated and combined treatment effects of specific types of psychosocial treatments relative to control and other treatments are needed. Future meta-analyses should take into account the complexity and breadth of available evidence.

Intensive group behavioral treatment (IGBT) for children with selective mutism: A preliminary randomized clinical trial.

OBJECTIVE: Very few controlled trials have evaluated targeted treatment methods for childhood selective mutism (SM); the availability of evidence-based services remains limited. This study is the first controlled trial to evaluate an intensive group behavioral treatment (IGBT) for children with SM. METHOD: Twenty-nine children with SM (5-9 years; 76% female; 35% ethnic minority) were randomized to immediate SM 5-day IGBT or to a 4-week waitlist with psychoeducational resources (WLP), and were assessed at Week 4 and again 8 weeks into the following school year. RESULTS: IGBT was associated with high satisfaction and low perceived barriers to treatment participation. At Week 4, 50% of the immediate IGBT condition and 0% of the WLP condition were classified as "clinical responders." Further, Time × Condition interactions were significant for social anxiety severity, verbal behavior in social situations, and global functioning (but not for SM severity, verbal behavior in home settings, or overall anxiety). School-year follow-up assessments revealed significant improvements across all outcomes. Eight weeks into the following school year, 46% of IGBT-treated children were free of an SM diagnosis. In addition, teachers in the post-IGBT school year rated less school impairment and more classroom verbal behavior relative to teachers in the pre-IGBT school year. CONCLUSIONS: Findings provide the first empirical support for the efficacy and acceptability of IGBT for SM. Further study is needed to examine mechanisms of IGBT response, and other effective SM treatment methods, in order to clarify which treatment formats work best for which affected children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Evidence Base Update on the Treatment of Early Childhood Anxiety and Related Problems.

The controlled evaluation of treatments for early childhood anxiety and related problems has been a relatively recent area of investigation, and accordingly, trials examining early childhood anxiety treatment have not been well represented in existing systematic reviews of youth anxiety treatments. This Evidence Base Update provides the first systematic review of evidence supporting interventions specifically for the treatment of early childhood anxiety and related problems. Thirty articles testing 38 treatments in samples with mean age < 7.9 years (N = 2,228 children) met inclusion criteria. We applied Southam-Gerow and Prinstein's (2014) review criteria, which classifies families of treatments according to one of five levels of empirical support-Well-Established, Probably Efficacious, Possibly Efficacious, Experimental, and of Questionable Efficacy. We found family-based cognitive-behavioral therapy (CBT) to be a Well-Established treatment, and Group Parent CBT and Group Parent CBT + Group Child CBT to both be Probably Efficacious treatments. In contrast, play therapy and attachment-based therapy are still only Experimental treatments for early childhood anxiety, relaxation training has Questionable Efficacy, and there is no evidence to date to speak to the efficacy of individual child CBT and/or medication in younger anxious children. All 3 currently supported interventions for early childhood anxiety entail exposure-based CBT with significant parental involvement. This conclusion meaningfully differs from conclusions for treating anxiety in older childhood that highlight the well-established efficacy of individual child CBT and/or medication and that question whether parental involvement in treatment enhances outcomes.

High-End Specificity of the Attention-Deficit/Hyperactivity Problems Scale of the Child Behavior Checklist for Ages 1.5-5 in a Sample of Young Children with Disruptive Behavior Disorders.

In practice, ADHD is commonly assessed with parent-reports in the absence of diagnostic interviews or behavioral observations, yet little is known about how accurately rating scales can independently detect ADHD. We used receiver operating characteristic analysis to evaluate the CBCL 1.5-5 Attention-Deficit/Hyperactivity Problems scale's ability to correctly classify the presence/absence of ADHD within a sample of young children with disruptive behavior disorders (N = 44), offering a conservative test of the scale's ability to distinguish ADHD symptoms from neighboring problems (i.e., "high-end specificity"). Across cut scores, the scale accurately differentiated between children with and without co-occurring ADHD (AUC = 0.83, SE = 0.07). Applying a cut score in the range of 61-64 yielded the most favorable balance across diagnostic utility properties (i.e., sensitivity = 0.71, specificity = 0.91, positive predictive power = 0.88, negative predictive power = 0.78). Findings provide empirical support to bolster confidence regarding use of this scale to assess early child ADHD, even in the context of complex diagnostic profiles.

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices.

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3N4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation.

Correlates of Adaptive Functioning in Minimally Verbal Children With Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) tend to have significant delays in adaptive functioning. In this study, the relationship between adaptive behavior and ASD symptomatology was investigated in minimally verbal, school-aged children with ASD (n = 333). Both the social affect (SA) and restricted and repetitive behavior (RRB) domains from the Autism Diagnostic Observation Schedule (ADOS) were analyzed in relation to adaptive skills. ADOS SA scores contributed unique variance to scores in each Vineland domain, though cognitive ability and age accounted for considerably more variance across domains. Results indicate that there is a significant, but small, association between social affect deficits and adaptive skills, challenging clinicians, educators, and caregivers to target adaptive skills in addition to more specific features of ASD.

Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology.

Obsessive Compulsive Disorder (OCD) is a common neuropsychiatric disorder with unknown molecular underpinnings. Identification of genetic and non-genetic risk factors has largely been elusive, primarily because of a lack of power. In contrast, neuroimaging has consistently implicated the cortico-striatal-thalamo-cortical circuits in OCD. Pharmacological treatment studies also show specificity, with consistent response of OCD symptoms to chronic treatment with serotonin reuptake inhibitors; although most patients are left with residual impairment. In theory, animal models could provide a bridge from the neuroimaging and pharmacology data to an understanding of pathophysiology at the cellular and molecular level. Several mouse models have been proposed using genetic, immunological, pharmacological, and optogenetic tools. These experimental model systems allow testing of hypotheses about the origins of compulsive behavior. Several models have generated behavior that appears compulsive-like, particularly excessive grooming, and some have demonstrated response to chronic serotonin reuptake inhibitors, establishing both face validity and predictive validity. Construct validity is more difficult to establish in the context of a limited understanding of OCD risk factors. Our current models may help us to dissect the circuits and molecular pathways that can elicit OCD-relevant behavior in rodents. We can hope that this growing understanding, coupled with developing technology, will prepare us when robust OCD risk factors are better understood.