Steve Rasmussen’s research while affiliated with Brown University and other places

Background: Obsessive compulsive disorder (OCD) is associated with elevated suicide risk, but the directionality of the association between OCD severity and suicidal ideation has not been established, which was the goal of this study. Methods: Participants (n = 325) were adults with either a current or past diagnosis of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) OCD who were assessed annually for suicidal ideation and OCD symptom severity for six years. Cross-lagged panel analyses statistically compared unidirectional and bidirectional models over time. Serious suicide-related adverse events were reported. Results: The best-fitting and most parsimonious model included paths predicting suicidal ideation from OCD symptom severity, but not vice versa. These results were confirmed by comparing a model with cross-lagged paths constrained equal to a freely estimated model. Higher OCD symptom severity in a given year was associated with a higher suicidal ideation severity in the subsequent year. Five suicide-related adverse events were reported throughout the duration of the study, including two suicide deaths and three suicide attempts. Limitations: The study relied on a single-item, annual measure of suicidal ideation in adults, with substantial variability in severity of suicide risk, and missing data increased with later observations in the study.

The study objective was to apply machine learning methodologies to identify predictors of remission in a longitudinal sample of 296 adults with a primary diagnosis of obsessive compulsive disorder (OCD). Random Forests is an ensemble machine learning algorithm that has been successfully applied to large-scale data analysis across vast biomedical disciplines, though rarely in psychiatric research or for application to longitudinal data. When provided with 795 raw and composite scores primarily from baseline measures, Random Forest regression prediction explained 50.8% (5000-run average, 95% bootstrap confidence interval [CI]: 50.3-51.3%) of the variance in proportion of time spent remitted. Machine performance improved when only the most predictive 24 items were used in a reduced analysis. Consistently high-ranked predictors of longitudinal remission included Yale-Brown Obsessive Compulsive Scale (Y-BOCS) items, NEO items and subscale scores, Y-BOCS symptom checklist cleaning/washing compulsion score, and several self-report items from social adjustment scales. Random Forest classification was able to distinguish participants according to binary remission outcomes with an error rate of 24.6% (95% bootstrap CI: 22.9-26.2%). Our results suggest that clinically-useful prediction of remission may not require an extensive battery of measures. Rather, a small set of assessment items may efficiently distinguish high- and lower-risk patients and inform clinical decision-making. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The ventral prefrontal cortex (vPFC) is involved in reinforcement-based learning and is associated with depression, obsessive-compulsive disorder, and addiction. Neuroimaging is increasingly used to develop models of vPFC connections, to examine white matter (WM) integrity, and to target surgical interventions, including deep brain stimulation. We used primate (Macaca nemestrina/Macaca fascicularis) tracing studies and 3D reconstructions of WM tracts to delineate the rules vPFC projections follow to reach their targets. vPFC efferent axons travel through the uncinate fasciculus, connecting different vPFC regions and linking different functional regions. The uncinate fasciculus also is a conduit for vPFC fibers to reach other cortical bundles. Fibers in the internal capsule are organized according to destination. Thalamic fibers from each vPFC region travel dorsal to their brainstem fibers. The results show regional differences in the trajectories of fibers from different vPFC areas. Overall, the medial/lateral vPFC position dictates the route that fibers take to enter major WM tracts, as well as the position within specific tracts: axons from medial vPFC regions travel ventral to those from more lateral areas. This arrangement, coupled with dorsal/ventral organization of thalamic/brainstem fibers through the internal capsule, results in a complex mingling of thalamic and brainstem axons from different vPFC areas. Together, these data provide the foundation for dividing vPFC WM bundles into functional components and for predicting what is likely to be carried at different points through each bundle. These results also help determine the specific connections that are likely to be captured at different neurosurgical targets.

This article describes the method and intake findings of the Brown Longitudinal Obsessive Compulsive Study, the first comprehensive prospective investigation of the naturalistic course of obsessive-compulsive disorder (OCD) in a large clinical sample using longitudinal research methodology. Intake data, collected between June 2001 and October 2004, are presented for 293 adult participants in a prospective, naturalistic study of OCD. Participants had a primary diagnosis of DSM-IV OCD and had sought treatment for the disorder. Our findings indicate that OCD typically has a gradual onset and a continuous course regardless of age at onset. There is a substantial lag between the onset of the disorder and initiation of treatment. OCD, which almost always coexists with other psychiatric symptoms, leads to serious social and occupational impairment. Compared with participants with late-onset OCD, early-onset participants had higher rates of lifetime panic disorder, eating disorders, and obsessive-compulsive personality disorder. The groups also differed on the types of obsessive-compulsive symptoms that were first noticed, as well as on rates of current obsessions and compulsions. The demographics, clinical characteristics, comorbidity rates, and symptom presentation of the sample are consistent with those reported for cross-sectional studies of OCD, including the DSM-IV Field Trial. The current sample has a number of advantages over previously collected prospective samples of OCD in that it is large, diagnostically well characterized, recruited from multiple settings, and treatment seeking. This unique data set will contribute to the identification of meaningful phenotypes in OCD based on stability of symptom dimensions, prospective course patterns, and treatment response.

High-frequency anterior capsular stimulation is a new, promising, and reversible neuromodulatory treatment in the research stage for patients with refractory obsessive-compulsive disorder (OCD). The mechanism of action is unknown but hypothesized to be secondary to interruption of the corticothalamostriatocortical circuit. (18)F-FDG PET was performed on 6 consecutive OCD patients preoperatively and after stimulation. The results were compared with those of 20 age- and sex-matched healthy volunteers by using both a standardized volume-of-interest-based approach for subcortical areas and statistical parametric mapping. Correlations were investigated with Yale-Brown Obsessive Compulsive Scale scores (Y-BOCS) and Hamilton Depression Rating Scale scores (HAM-D). Chronic anterior capsular electrostimulation resulted in a further decrease of prefrontal metabolic activity, especially in the subgenual anterior cingulate (P < 0.001). Correlation analysis demonstrated that decreases in Y-BOCS and HAM-D with anterior capsular electrostimulation were inversely related to the metabolic activity changes in the left ventral striatum, left amygdala, and left hippocampus (P < 0.01). Preoperative resting metabolic activity in the subgenual anterior cingulate was predictive of therapeutic response (P = 0.001). These observations provide evidence that the subgenual anterior cingulate and ventral striatum have a key role in the neuronal circuitry involved in the pathophysiology of OCD with associated major depression and in the neuromodulatory mechanism of anterior capsular stimulation.