Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents.

BACKGROUND: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. METHODS: Adolescents (N = 90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. DISCUSSION: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).

Year of Zoom in a Year of Doom: Lessons Learned Delivering ERP Remotely During the COVID-19 Pandemic.

In response to the COVID-19 pandemic and consequential shutdown measures, many mental health professionals started providing therapy to patients exclusively via telehealth. Our research center, which specializes in studying and treating obsessive-compulsive disorder (OCD), historically has provided in-person exposure and response prevention (ERP) to adults with OCD, but shifted to telehealth during the pandemic. Unlike in other modes of talk therapy, ERP's emphasis on therapist-supervised exposures presented unique opportunities and challenges to delivering treatment entirely via a virtual platform. This paper provides case examples to illustrate lessons we learned delivering ERP exclusively via telehealth in New York from March 2020 through June 2021 and offers recommendations for future study and practice. Though we observed a number of drawbacks to fully remote ERP, we also discovered advantages to delivering ERP this way, meriting additional research attention.

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

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

Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

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

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

Defining functional brain networks underlying obsessive-compulsive disorder (OCD) using treatment-induced neuroimaging changes: a systematic review of the literature.

Approximately 2%-3% of the population suffers from obsessive-compulsive disorder (OCD). Several brain regions have been implicated in the pathophysiology of OCD, but their various contributions remain unclear. We examined changes in structural and functional neuroimaging before and after a variety of therapeutic interventions as an index into identifying the underlying networks involved. We identified 64 studies from 1990 to 2020 comparing pretreatment and post-treatment imaging of patients with OCD, including metabolic and perfusion, neurochemical, structural, functional and connectivity-based modalities. Treatment class included pharmacotherapy, cognitive-behavioural therapy/exposure and response prevention, stereotactic lesions, deep brain stimulation and transcranial magnetic stimulation. Changes in several brain regions are consistent and correspond with treatment response despite the heterogeneity in treatments and neuroimaging modalities. Most notable are decreases in metabolism and perfusion of the caudate, anterior cingulate cortex, thalamus and regions of prefrontal cortex (PFC) including the orbitofrontal cortex (OFC), dorsolateral PFC (DLPFC), ventromedial PFC (VMPFC) and ventrolateral PFC (VLPFC). Modulating activity within regions of the cortico-striato-thalamo-cortical system may be a common therapeutic mechanism across treatments. We identify future needs and current knowledge gaps that can be mitigated by implementing integrative methods. Future studies should incorporate a systematic, analytical approach to testing objective correlates of treatment response to better understand neurophysiological mechanisms of dysfunction.

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

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

Behavioral avoidance predicts treatment outcome with exposure and response prevention for obsessive-compulsive disorder.

BACKGROUND: Many individuals with obsessive-compulsive disorder (OCD) display behavioral avoidance related to their obsessional thoughts and compulsive behaviors. However, how these avoidance behaviors impact treatment outcomes with exposure and response prevention (EX/RP) remains unclear. We examined pretreatment avoidance behaviors as predictors of EX/RP outcomes. METHODS: Data came from a randomized controlled trial of augmentation strategies for inadequate response to serotonin reuptake inhibitors comparing EX/RP (N = 40), risperidone (N = 40), and placebo (N = 20). Baseline avoidance was rated with the avoidance item from the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Primary analyses examined avoidance behaviors as predictors of EX/RP outcomes. To test specificity, we explored whether avoidance also related to outcomes among patients receiving risperidone and placebo. RESULTS: More than half (69%) of the full sample had moderate or severe avoidance behaviors at baseline. In EX/RP, controlling for baseline severity, pretreatment avoidance predicted posttreatment YBOCS symptoms (ß = 0.45, P < .01). Avoidant individuals were less likely to achieve remission with EX/RP (odds ratio = 0.04, 95% confidence interval [CI] range 0.01-0.28, P = .001). Baseline avoidance was also associated with degree of patient adherence to between-session EX/RP assignments, which mediated the relationship between baseline avoidance and EX/RP outcomes (P < .05). Baseline avoidance did not predict outcomes or wellness among patients receiving risperidone or placebo. CONCLUSIONS: These results suggest that avoidance behaviors are an important clinical factor in EX/RP outcomes and indicate that assessing avoidance may provide an efficient method for predicting EX/RP outcomes. Avoidance may be particularly relevant in EX/RP as compared to medication treatment, though future replication of these initial results is required.

Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive-compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala-ventromedial prefrontal cortex (BLA-vmPFC) communication would predict CBT outcome in patients with OCD. METHODS: We investigated whether BLA-vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA-vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants. RESULTS: We included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA-vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA-vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT. LIMITATIONS: We used a sample of convenience, and all patients were receiving pharmacological treatment for OCD. CONCLUSION: In this large sample of patients with OCD, BLA-vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA-vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders.

Temporal discounting across three psychiatric disorders: Anorexia nervosa, obsessive compulsive disorder, and social anxiety disorder.

BACKGROUND: Temporal discounting refers to the tendency for rewards to lose value as the expected delay to receipt increases. Individuals with anorexia nervosa (AN) have been found to show reduced temporal discounting rates, indicating a greater preference for delayed rewards compared to healthy peers. Obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD) commonly co-occur with AN, and anxiety has been related to development and prognosis of AN. We examined whether reduced temporal discounting is present across these potentially related disorders, and explored the relationship between temporal discounting and anxiety transdiagnostically. METHODS: One hundred ninety six individuals (75 healthy controls (HC); 50 OCD; 27 AN; 44 SAD) completed two temporal discounting tasks in which they chose between smaller-sooner and larger-later monetary rewards. Two measures of discounting-discount rate and discount factor-were compared between diagnostic groups, and associations with anxious traits were examined. RESULTS: Individuals with AN showed decreased temporal discounting compared to HC. OCD and SAD groups did not differ significantly from HC. Across the sample, anxiety was associated with decreased discounting; more anxious individuals showed a greater preference for delayed reward. CONCLUSIONS: We replicated the findings that individuals with AN show an increased preference for delayed reward relative to HC and that individuals with OCD do not differ from HC. We also showed that individuals with SAD do not differ from HC in discounting. Across this large sample, two measures of anxious temperament were associated with temporal discounting. These data raise new questions about the relationship between this dimensional trait and psychopathology.

The Role of Response Inhibition in Medicated and Unmedicated Obsessive-Compulsive Disorder Patients: Evidence from the Stop-Signal Task.

BACKGROUND: Numerous studies have investigated response inhibition (RI) in obsessive-compulsive disorder (OCD), with many reporting that OCD patients demonstrate deficits in RI as compared to controls. However, reported effect sizes tend to be modest and results have been inconsistent, with some studies finding intact RI in OCD. To date, no study has examined the effect of medications on RI in OCD patients. METHODS: We analyzed results from a stop-signal task to probe RI in 65 OCD patients (32 of whom were medicated) and 58 healthy controls (HCs). RESULTS: There was no statistically significant difference in stop-signal reaction time between the OCD group and the HC group, or between the medicated and unmedicated OCD patients. However, variability was significantly greater in the medicated OCD group compared to the unmedicated group. CONCLUSIONS: These results indicate that some samples of OCD patients do not have deficits in RI, making it unlikely that deficient RI underlies repetitive behaviors in all OCD patients. Future research is needed to fully elucidate the impact of medication use on stop-signal performance. Implications for future research on the cognitive processes underlying repetitive thoughts and behaviors are discussed.

The effect of treatment on quality of life and functioning in OCD.

BACKGROUND: Given that obsessive compulsive disorder (OCD) is associated with impaired quality of life (QoL) and functioning, it is important examine whether therapeutic recovery from OCD leads to improvements on these important secondary outcomes. Only a few studies have examined how measures of OCD symptom severity relate to QoL and functioning among patients receiving treatment for OCD. METHODS: OCD severity was measured with the Obsessive-Compulsive Inventory-Revised (OCI-R), a self-report scale of OCD, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), an interview measure of OCD. Participants were 100 adults with a primary diagnosis of OCD on serotonin reuptake inhibitors (SRIs) enrolled in a randomized clinical trial comparing SRI augmentation with either exposure and response prevention (EX/RP) therapy, risperidone, or pill placebo. At baseline, mid-treatment, and post-treatment, patients completed assessments for OCD symptoms and QoL/functioning measures. Multilevel modeling was used to assess changes in QoL/functioning over the course of treatment and to compare such changes across treatment conditions. RESULTS: Improvements in QoL/functioning were significantly greater among those receiving EX/RP compared to those receiving risperidone. Compared to pill placebo, EX/RP performed better on measures of functioning but not QoL. Greater improvement in individual OCI-R scores was associated with greater improvements in QoL/functioning, regardless of condition. In addition, Y-BOCS scores appeared to moderate improvements in QoL over the course of all treatment conditions, such that those with higher Y-BOCS scores showed the greatest improvements in QoL over time. CONCLUSIONS: Improvements in QoL/functioning were associated with reduction in OCD symptom severity. The implications on OCD treatment and clinical research are discussed.

PREPULSE INHIBITION DEFICITS ONLY IN FEMALES WITH OBSESSIVE-COMPULSIVE DISORDER.

BACKGROUND: Deficits in sensorimotor gating have been hypothesized to underlie the inability to inhibit repetitive thoughts and behaviors. To test this hypothesis, this study assessed prepulse inhibition (PPI), a measure of sensorimotor gating, across three psychiatric disorders (obsessive-compulsive disorder [OCD], social anxiety disorder [SAD], and anorexia nervosa [AN]) whose clinical presentations include repetitive thoughts and behaviors METHODS: We tested acoustic PPI in unmedicated individuals with OCD (n = 45), SAD (n = 37), and AN (n = 26), and compared their results to matched healthy volunteers (n = 62). All participants completed a structured clinical interview and a clinical assessment of psychiatric symptom severity. RESULTS: Percent PPI was significantly diminished in females with OCD compared to healthy female volunteers (P = .039). No other differences between healthy volunteers and participants with disorders (male or female) were observed. Percent PPI was not correlated with severity of obsessions and compulsions, as measured by the Yale-Brown Obsessive Compulsive Scale. CONCLUSIONS: This is the first study to assess PPI in participants with SAD or AN, and the largest study to assess PPI in participants with OCD. We found PPI deficits only in females with OCD, which suggests that the cortico-striato-pallido-thalamic and pontine circuitry (believed to underlie PPI) differs between males and females with OCD. Given that PPI deficits were only present in females with OCD and not related to repetitive thoughts and behaviors, our results do not support the hypothesis that sensorimotor gating deficits, as measured by PPI, underlie the inability to inhibit repetitive thoughts and behaviors in individuals with OCD, SAD, and AN.

Residential treatment outcomes for adolescents with obsessive-compulsive disorder.

OBJECTIVE: We examined outcomes from a residential treatment program emphasizing exposure and response prevention (ERP) to determine if the typically robust response to this treatment in outpatient settings extends to patients treated in this unique context. METHOD: One hundred and seventy-two adolescents with primary Obsessive-compulsive disorder (OCD) completed measures at admission and discharge. Almost all (92.4%) participants had at least two diagnoses and nearly half (44.2%) had three or more. Treatment consisted of intensive ERP (i.e., approximately 26.5 hr per week), additional cognitive behavioral therapy interventions, and medication management within a residential setting. In contrast to the samples reported on in the vast majority of other pediatric OCD trials, participants in the current study were living apart from their families and were immersed within the treatment setting, with staff members available at all times. RESULTS: Paired sample t-tests revealed significant decreases in OCD and depression severity. CONCLUSIONS: Results suggest that residential treatment for adolescents with OCD using a multimodal approach emphasizing ERP can be effective for complex cases with significant comorbidity. Results were comparable with several randomized controlled trials.

Interpersonal functioning in obsessive-compulsive personality disorder.

The core symptoms of obsessive-compulsive personality disorder (OCPD) often lead to interpersonal difficulties. However, little research has explored interpersonal functioning in OCPD. This study examined interpersonal problems, interpersonal sensitivities, empathy, and systemizing, the drive to analyze and derive underlying rules for systems, in a sample of 25 OCPD individuals, 25 individuals with comorbid OCPD and obsessive-compulsive disorder (OCD), and 25 healthy controls. We found that OCPD individuals reported hostile-dominant interpersonal problems and sensitivities with warm-dominant behavior by others, whereas OCPD+OCD individuals reported submissive interpersonal problems and sensitivities with warm-submissive behavior by others. Individuals with OCPD, with and without OCD, reported less empathic perspective taking relative to healthy controls. Finally, we found that OCPD males reported a higher drive to analyze and derive rules for systems than OCPD females. Overall, results suggest that there are interpersonal deficits associated with OCPD and the clinical implications of these deficits are discussed.

Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder.

Cortico-striato-thalamo-cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive-Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional-connectivity MRI (rs-fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs-fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs-fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity.

Confronting fear using exposure and response prevention for anorexia nervosa: A randomized controlled pilot study.

OBJECTIVE: Anorexia nervosa (AN) is a severe illness with high rates of relapse. Exposure and Response Prevention for AN (AN-EXRP) is a new approach that specifically addresses maladaptive eating behavior by targeting eating-related fear and anxiety. The aim of this study was to evaluate AN-EXRP as an adjunctive strategy to improve eating behavior during weight restoration, at a pivotal moment when treatment goals shift toward relapse prevention. METHOD: A randomized controlled trial was conducted to compare AN-EXRP with a comparison condition, Cognitive Remediation Therapy (CRT). Hospitalized patients with AN (n = 32) who had achieved weight restoration to a BMI > 18.5 kg/m(2) received 12 sessions of either AN-EXRP or CRT. Outcome was assessed by change in caloric intake in an objective assessment of eating behavior. RESULTS: The average test meal caloric intake of participants who received AN-EXRP increased from 352 ± 263 kcal at baseline to 401 ± 215 kcal post-treatment, while that of participants who received CRT decreased from 501 ± 232 kcal at baseline to 424 ± 221 kcal post-treatment [t(28) = 2.5, p = .02]. Improvement in intake was significantly associated with improvement in eating-related anxiety (Spearman's ρ = 0.40, p = .03). DISCUSSION: These data demonstrate that AN-EXRP, compared to a credible comparison intervention, is associated with better caloric intake in a laboratory meal over time in AN. Additional studies are required to determine whether incorporation of these techniques into a longer treatment program leads to enduring and clinically significant change.

Evidence-Based Supported Employment for Individuals With Obsessive-Compulsive Disorder.

Individuals with obsessive-compulsive disorder (OCD), a chronic and disabling psychiatric disorder, experience high rates of occupational impairment. OCD symptoms commonly affect individuals' vocational aspirations and result in disability and the need for financial support, problems that are not addressed by current clinical practice guideline recommendations for treating OCD. This Open Forum highlights the need to address occupational impairment caused by OCD and makes the case for formally evaluating whether evidence-based supported employment can help individuals with OCD find and succeed in meaningful work.

Assessing harmonized intelligence measures in a multinational study.

Studies examining the neurocognitive and circuit-based etiology of psychiatric illness are moving toward inclusive, global designs. A potential confounding effect of these associations is general intelligence; however, an internationally validated, harmonized intelligence quotient (IQ) measure is not available. We describe the procedures used to measure IQ across a five-site, multinational study and demonstrate the harmonized measure's cross-site validity. Culturally appropriate intelligence measures were selected: four short-form Wechsler intelligence tests (Brazil, Netherlands, South Africa, United States) and the Binet Kamat (India). Analyses included IQ scores from 255 healthy participants (age 18-50; 42% male). Regression analyses tested between-site differences in IQ scores, as well as expected associations with sociodemographic factors (sex, socioeconomic status, education) to assess validity. Harmonization (e.g., a priori selection of tests) yielded the compatibility of IQ measures. Higher IQ was associated with higher socioeconomic status, suggesting good convergent validity. No association was found between sex and IQ at any site, suggesting good discriminant validity. Associations between higher IQ and higher years of education were found at all sites except the United States. Harmonized IQ scores provide a measure of IQ with evidence of good validity that can be used in neurocognitive and circuit-based studies to control for intelligence across global sites.