Publications by authors named "Benjamin D Greenberg"

114 Publications

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Mov Disord 2021 May 4. Epub 2021 May 4.

Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.

Objective: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.

Methods: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.

Results: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.

Conclusions: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28593DOI Listing
May 2021

Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder.

Neurosurgery 2021 Mar 8. Epub 2021 Mar 8.

Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, Rhode Island, USA.

Background: Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration.

Objective: To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo.

Methods: A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies.

Results: A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery.

Conclusion: LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.
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http://dx.doi.org/10.1093/neuros/nyab050DOI Listing
March 2021

Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder.

Neurosurgery 2021 Mar 8. Epub 2021 Mar 8.

Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, Rhode Island, USA.

Background: Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration.

Objective: To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo.

Methods: A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies.

Results: A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery.

Conclusion: LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.
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http://dx.doi.org/10.1093/neuros/nyab050DOI Listing
March 2021

The COBRE Center for Neuromodulation (CCN) at Butler Hospital: Clinical-Translational Research in Human Brain Stimulation.

R I Med J (2013) 2021 Mar 1;104(2):30-33. Epub 2021 Mar 1.

Butler Hospital, Providence RI; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University.

The COBRE Center for Neuromodulation (CCN) at Butler Hospital supports clinical research in neuromodulation and investigators' career development in this field. The work couples brain stimulation methods with readouts of brain activity (e.g., using various neuroimaging, behavioral, and physiological assessment methods) in clinical or clinically relevant populations. Its guiding principle is that for noninvasive brain stimulation to gain efficacy and implementation, it is essential to better characterize clinically relevant target circuits and mechanisms of action. The CCN includes a Design and Analysis Core (DAC) to support rigorous and innovative experimental design and data analytic strategies and a Neuromodulation and Neuroimaging Core (NNC) to facilitate the acquisition and processing of high-quality data using noninvasive neurostimulation and neuroimaging methods. This article will describe the CCN's research focus and how it enhances research capacity in neuromodulation in our state. It will introduce our current investigator Project Leaders, their projects, and our pilot project program. It will also detail the CCN's links to Centers and research cores in Rhode Island researching allied areas of clinical neuroscience, neurology, psychiatry, and psychology, current collaborative efforts across those centers, and opportunities to collaborate in research and training.
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March 2021

A Secondary Analysis on Effects of Theta Burst Transcranial Magnetic Stimulation to Reduce Anger in Veterans With Posttraumatic Stress Disorder.

Neuromodulation 2020 Sep 17. Epub 2020 Sep 17.

VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Medical Center and Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, 02906, USA.

Introduction: Anger is an important clinical feature of posttraumatic stress disorder (PTSD) that can hamper recovery. We recently reported that intermittent theta burst stimulation (iTBS) demonstrated preliminary efficacy to reduce symptoms of posttraumatic stress disorder and major depression; here, we performed a secondary analysis testing whether iTBS reduced symptoms of anger over the course of iTBS treatment and compared to sham stimulation.

Materials And Methods: Fifty veterans with chronic PTSD received ten daily sessions of sham-controlled, double-blind iTBS (1800 pulses/session, once per weekday) targeting the right dorsolateral prefrontal cortex (intent-to-treat = 25 per group). Participants who completed the double-blind phase were offered another ten sessions of unblinded iTBS. Participants completed the Dimensions of Anger Reactions scale at pre-iTBS baseline, treatment midpoints, and endpoints of the blinded and unblinded phases, and at one-month after the last stimulation session. Correlations between anger, PTSD, depression, and sleep were also explored.

Results: After the first week, during the double-blind phase, participants randomized to active stimulation reported significantly reduced anger compared to sham stimulation (p = 0.04). Participants initially randomized to sham appeared to catch-up to the point they no longer differed from those initially randomized to active iTBS when they received iTBS during the unblinded phase (p = 0.14). Anger reduction was maintained at one-month after iTBS in participants initially randomized to active stimulation (i.e., total of four weeks of iTBS).

Conclusions: This secondary analysis suggests that iTBS might reduce anger in veterans with PTSD. Future studies focused on more granular level anger outcomes and effects of number of stimulation sessions are needed.
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http://dx.doi.org/10.1111/ner.13256DOI Listing
September 2020

A Brief Report on an 8-Week Course of Mindfulness-based Care for Chronic Pain in the Treatment of Veterans With Back Pain: Barriers Encountered to Treatment Engagement and Lessons Learned.

Med Care 2020 09;58 Suppl 2 9S:S94-S100

Mental Health and Behavioral Sciences Service, Department of Veteran Affairs Medical Center, Providence VA Medical Center.

Background: Chronic pain and associated symptoms are debilitating for veterans. Medical costs of treatments are high and current treatment options, most notably with opioid medications, have been associated with significant risk. Mindfulness-based interventions appear promising for chronic pain, but require additional testing in veteran care settings.

Objective: This project was designed to test the feasibility of engaging and retaining veterans with chronic lower back pain in a new mindfulness protocol tailored for veterans, mindfulness-based care for chronic pain (MBCP). Clinical outcomes were also assessed.

Design: An open pilot trial of an 8-week MBCP course that included meditation, gentle yoga, and psychoeducation.

Subjects: Twenty-two veterans (mean age=49.77; 18% women) were recruited from a VA Medical Center in the Northeastern US. After screening for inclusion/exclusion criteria, 20 were eligible at baseline.

Measures: Veterans were assessed at baseline and postintervention for functional impairment, pain intensity and bothersomeness, depression, and mindfulness.

Results: The average number of sessions completed was 5; only 4 (20%) attended all sessions. Eleven of the 20 participants (55%) attended 5 or more sessions and had complete preintervention and postintervention visits. Five of the 11 had a clinically meaningful decrease in pain intensity and in depressive symptoms, while 6 of 11 had a meaningful decrease in pain bothersomeness and functional impairment.

Conclusions: It was challenging to enroll and retain participants in this study, even with our intervention designed for veterans. We discuss possible adaptations and refinements in MBCP for veterans with chronic pain to enhance feasibility and improve upon these interventions.
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http://dx.doi.org/10.1097/MLR.0000000000001377DOI Listing
September 2020

Prolonged avoidance training exacerbates OCD-like behaviors in a rodent model.

Transl Psychiatry 2020 07 3;10(1):212. Epub 2020 Jul 3.

Departments of Psychiatry and Anatomy & Neurobiology, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, 00936, USA.

Obsessive-compulsive disorder (OCD) is characterized by compulsive behaviors that often resemble avoidance of perceived danger. OCD can be treated with exposure-with-response prevention (ERP) therapy in which patients are exposed to triggers but are encouraged to refrain from compulsions, to extinguish compulsive responses. The compulsions of OCD are strengthened by many repeated exposures to triggers, but little is known about the effects of extended repetition of avoidance behaviors on extinction. Here we assessed the extent to which overtraining of active avoidance affects subsequent extinction-with-response prevention (Ext-RP) as a rodent model of ERP, in which rats are extinguished to triggers, while the avoidance option is prevented. Male rats conditioned for 8d or 20d produced similar avoidance behavior to a tone paired with a shock, however, the 20d group showed a severe impairment of extinction during Ext-RP, as well as heightened anxiety. Furthermore, the majority of overtrained (20d) rats (75%) exhibited persistent avoidance following Ext-RP. In the 8d group, only a minority of rats (37%) exhibited persistent avoidance, and this was associated with elevated activity (c-Fos) in the prelimbic cortex and nucleus accumbens. In the 20d group, the minority of non-persistent rats (25%) showed elevated activity in the insular-orbital cortex and paraventricular thalamus. Lastly, extending the duration of Ext-RP prevented the deleterious effects of overtraining on extinction and avoidance. These rodent findings suggest that repeated expression of compulsion-like behaviors biases individuals toward persistent avoidance and alters avoidance circuits, thereby reducing the effectiveness of current extinction-based therapies.
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http://dx.doi.org/10.1038/s41398-020-00892-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334221PMC
July 2020

Mapping PTSD symptoms to brain networks: a machine learning study.

Transl Psychiatry 2020 06 18;10(1):195. Epub 2020 Jun 18.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, 02906, USA.

Posttraumatic Stress Disorder (PTSD) is a prevalent and debilitating condition with complex and variable presentation. While PTSD symptom domains (intrusion, avoidance, cognition/mood, and arousal/reactivity) correlate highly, the relative importance of these symptom subsets often differs across patients. In this study, we used machine learning to derive how PTSD symptom subsets differ based upon brain functional connectivity. We acquired resting-state magnetic resonance imaging in a sample (N = 50) of PTSD patients and characterized clinical features using the PTSD Checklist for DSM-5 (PCL-5). We compared connectivity among 100 cortical and subcortical regions within the default mode, salience, executive, and affective networks. We then used principal component analysis and least-angle regression (LARS) to identify relationships between symptom domain severity and brain networks. We found connectivity predicted PTSD symptom profiles. The goodness of fit (R) for total PCL-5 score was 0.29 and the R for intrusion, avoidance, cognition/mood, and arousal/reactivity symptoms was 0.33, 0.23, -0.01, and 0.06, respectively. The model performed significantly better than chance in predicting total PCL-5 score (p = 0.030) as well as intrusion and avoidance scores (p = 0.002 and p = 0.034). It was not able to predict cognition and arousal scores (p = 0.412 and p = 0.164). While this work requires replication, these findings demonstrate that this computational approach can directly link PTSD symptom domains with neural network connectivity patterns. This line of research provides an important step toward data-driven diagnostic assessments in PTSD, and the use of computational methods to identify individual patterns of network pathology that can be leveraged toward individualized treatment.
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http://dx.doi.org/10.1038/s41398-020-00879-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303205PMC
June 2020

Transient aphasia induced by intermittent theta burst stimulation.

Brain Stimul 2020 Jul - Aug;13(4):941-942. Epub 2020 Mar 25.

VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI, 02908, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Butler Hospital, Providence, RI, USA.

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http://dx.doi.org/10.1016/j.brs.2020.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343258PMC
March 2020

Informing Further Research in the Use of Brain Stimulation in Psychiatric Disorders: Response to Syed and Smith.

Am J Psychiatry 2020 05;177(5):466-467

The Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, R.I., and the Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, R.I.

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http://dx.doi.org/10.1176/appi.ajp.2019.19101052rDOI Listing
May 2020

Functional disruption in prefrontal-striatal network in obsessive-compulsive disorder.

Psychiatry Res Neuroimaging 2020 06 22;300:111081. Epub 2020 Apr 22.

Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA.

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. While a cortico-striatal-limbic network has been implicated in the pathophysiology of OCD, the neural correlates of this network in OCD are not well understood. In this study, we examined resting state functional connectivity among regions within the cortico-striatal-limbic OCD neural network, including the rostral anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, thalamus and caudate, in 44 OCD and 43 healthy participants. We then examined relationships between OCD neural network connectivity and OCD symptom severity in OCD participants. OCD relative to healthy participants showed significantly greater connectivity between the left caudate and bilateral dorsolateral prefrontal cortex. We also found a positive correlation between left caudate-bilateral dorsolateral prefrontal cortex connectivity and depression scores in OCD participants, such that greater positive connectivity was associated with more severe symptoms. This study makes a significant contribution to our understanding of functional networks and their relationship with depression in OCD.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266720PMC
June 2020

Functional Disruption of Cerebello-thalamo-cortical Networks in Obsessive-Compulsive Disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 04 13;5(4):438-447. Epub 2019 Dec 13.

Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. Neuroimaging studies have implicated altered connectivity among the functional networks of the cerebral cortex in the pathophysiology of OCD. However, there has been no comprehensive investigation of the cross-talk between the cerebellum and functional networks in the cerebral cortex.

Methods: This functional neuroimaging study was completed by 44 adult participants with OCD and 43 healthy control participants. We performed large-scale data-driven brain network analysis to identify functional connectivity patterns using resting-state functional magnetic resonance imaging data.

Results: Participants with OCD showed lower functional connectivity within the somatomotor network and greater functional connectivity among the somatomotor network, cerebellum, and subcortical network (e.g., thalamus and pallidum; all p < .005). Network-based statistics analyses demonstrated one component comprising connectivity within the somatomotor network that showed lower connectivity and a second component comprising connectivity among the somatomotor network, and motor regions in particular, and the cerebellum that showed greater connectivity in participants with OCD relative to healthy control participants. In participants with OCD, abnormal connectivity across both network-based statistics-derived components positively correlated with OCD symptom severity (p = .006).

Conclusions: To our knowledge, this study is the first comprehensive investigation of large-scale network alteration across the cerebral cortex, subcortical regions, and cerebellum in OCD. Our findings highlight a critical role of the cerebellum in the pathophysiology of OCD.
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http://dx.doi.org/10.1016/j.bpsc.2019.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150632PMC
April 2020

Obsessive-Compulsive Personality Symptoms Predict Poorer Response to Gamma Ventral Capsulotomy for Intractable OCD.

Front Psychiatry 2019 9;10:936. Epub 2020 Jan 9.

Department & Institute of Psychiatry, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Gamma ventral capsulotomy (GVC) is a radiosurgical procedure which aims to create lesions in the ventral part of the anterior limb of the internal capsule (ALIC). It has been used as a treatment option for patients with intractable obsessive-compulsive disorder (OCD) who do not respond to several first-line treatments attempts. However, changes in personality disorder symptoms after GVC have not been investigated. The aims of this study are to investigate changes in personality disorder symptoms after GVC and to search for baseline personality disorder symptoms that may predict clinical response to GVC. Fourteen treatment-intractable OCD patients who underwent GVC completed the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) at baseline and one year after the procedure. Wilcoxon signed-rank test was performed to investigate personality disorder symptom changes before and after surgery. Linear regression models were utilized to predict treatment response, using baseline personality disorder symptoms as independent variables. We did not observe any quantitative changes in personality disorder symptoms after GVC, compared with baseline. Higher severity of obsessive-compulsive personality disorder symptoms at baseline was correlated with worse treatment response after GVC for OCD (β = -0.085, t-value = -2.52, p-value = 0.027). These findings advocate for the safety of the GVC procedure in this specific population of intractable OCD patients, in terms of personality disorder symptom changes. They also highlight the importance of taking into account the severity of obsessive-compulsive personality disorder symptoms when GVC is indicated for intractable OCD patients.
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http://dx.doi.org/10.3389/fpsyt.2019.00936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962231PMC
January 2020

General personality dimensions, impairment and treatment response in obsessive-compulsive disorder.

Personal Ment Health 2020 05 20;14(2):186-198. Epub 2019 Dec 20.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

General personality dimensions are associated with clinical severity and treatment response in individuals with depression and many anxiety disorders, but little is known about these relationships in individuals with obsessive-compulsive disorder (OCD). Individuals in the current study included 705 adults with OCD who had participated in family and genetic studies of the disorder. Participants self-completed the Neuroticism, Extraversion, Openness Personality Inventory or Neuroticism, Extraversion, Openness Five-Factor Inventory-3. Relationships between personality scores, and subjective impairment and OCD treatment response, were evaluated. The odds of subjective impairment increased with (unit increase in) the neuroticism score (odds ratio, OR = 1.03; 95% CI = 1.01-1.04; p < 0.01) and decreased with extraversion scores (OR = 0.98; 95% CI = 0.96-0.99; p < 0.01). The odds of reporting a good response to serotonin/selective serotonin reuptake inhibitors (OR = 1.02; 95% CI = 1.01-1.04; p < 0.01) or cognitive behavioural therapy (OR = 1.03; 95% CI = 1.01-1.05; p < 0.01) increased with the extraversion score. The magnitude of these relationships did not change appreciably after adjusting for other clinical features related to one or more of the personality dimensions. The findings suggest that neuroticism and extraversion are associated with subjective impairment, and that extraversion is associated with self-reported treatment response, in individuals with OCD. © 2019 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pmh.1472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202992PMC
May 2020

Trichotillomania comorbidity in a sample enriched for familial obsessive-compulsive disorder.

Compr Psychiatry 2019 10 31;94:152123. Epub 2019 Aug 31.

Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, United States of America. Electronic address:

Background: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification.

Methods: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders.

Results: TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4).

Conclusions: TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.
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http://dx.doi.org/10.1016/j.comppsych.2019.152123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980465PMC
October 2019

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder.

Am J Psychiatry 2019 11 24;176(11):939-948. Epub 2019 Jun 24.

The Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, and the Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, R.I.

Objective: Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD.

Methods: Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors.

Results: Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity.

Conclusions: iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.
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http://dx.doi.org/10.1176/appi.ajp.2019.18101160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824981PMC
November 2019

Immune-Related Comorbidities in Childhood-Onset Obsessive Compulsive Disorder: Lifetime Prevalence in the Obsessive Compulsive Disorder Collaborative Genetics Association Study.

J Child Adolesc Psychopharmacol 2019 10 6;29(8):615-624. Epub 2019 Jun 6.

Department of Psychiatry, Faculty of Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.

To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL). Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1-5.2]% vs. 1.0%-2.0%,  = 1.491,  < 0.001,  = 1389), encephalitis or meningitis (1.4 [0.9-2.1]% vs. 0.1%-0.4%,  = 5.913,  < 0.001,  = 1393), rheumatoid arthritis (1.1 [0.6-2.0]% vs. 0.2%-0.4%,  = 3.416,  < 0.001,  = 949) and rheumatic fever (0.6 [0.3-1.2]% vs. 0.1%-0.2%,  = 3.338,  < 0.001,  = 1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5 ± 0.9 vs. 2.3 ± 1.0,  = 3.183,  = 0.002,  = 822). These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.
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http://dx.doi.org/10.1089/cap.2018.0140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786333PMC
October 2019

Use of machine learning in predicting clinical response to transcranial magnetic stimulation in comorbid posttraumatic stress disorder and major depression: A resting state electroencephalography study.

J Affect Disord 2019 06 30;252:47-54. Epub 2019 Mar 30.

Butler Hospital, Providence, RI 02906, United States; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI 02906, United States.

Background: Repetitive transcranial magnetic stimulation (TMS) is clinically effective for major depressive disorder (MDD) and investigational for other conditions including posttraumatic stress disorder (PTSD). Understanding the mechanisms of TMS action and developing biomarkers predicting response remain important goals. We applied a combination of machine learning and electroencephalography (EEG), testing whether machine learning analysis of EEG coherence would (1) predict clinical outcomes in individuals with comorbid MDD and PTSD, and (2) determine whether an individual had received a TMS course.

Methods: We collected resting-state 8-channel EEG before and after TMS (5 Hz to the left dorsolateral prefrontal cortex). We used Lasso regression and Support Vector Machine (SVM) to test the hypothesis that baseline EEG coherence predicted the outcome and to assess if EEG coherence changed after TMS.

Results: In our sample, clinical response to TMS were predictable based on pretreatment EEG coherence (n = 29). After treatment, 13/29 had more than 50% reduction in MDD self-report score 12/29 had more than 50% reduction in PTSD self-report score. For MDD, area under roc curve was for MDD was 0.83 (95% confidence interval 0.69-0.94) and for PTSD was 0.71 (95% confidence interval 0.54-0.87). SVM classifier was able to accurately assign EEG recordings to pre- and post-TMS treatment. The accuracy for Alpha, Beta, Theta and Delta bands was 75.4 ± 1.5%, 77.4 ± 1.4%, 73.8 ± 1.5%, and 78.6 ± 1.4%, respectively, all significantly better than chance (50%, p < 0.001).

Limitation: Limitations of this work include lack of sham condition, modest sample size, and a sparse electrode array. Despite these methodological limitations, we found validated and clinically meaningful results.

Conclusions: Machine learning successfully predicted non-response to TMS with high specificity, and identified pre- and post-TMS status using EEG coherence. This approach may provide mechanistic insights and may also become a clinically useful screening tool for TMS candidates.
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http://dx.doi.org/10.1016/j.jad.2019.03.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520189PMC
June 2019

Use of machine learning in predicting clinical response to transcranial magnetic stimulation in comorbid posttraumatic stress disorder and major depression: A resting state electroencephalography study.

J Affect Disord 2019 06 30;252:47-54. Epub 2019 Mar 30.

Butler Hospital, Providence, RI 02906, United States; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI 02906, United States.

Background: Repetitive transcranial magnetic stimulation (TMS) is clinically effective for major depressive disorder (MDD) and investigational for other conditions including posttraumatic stress disorder (PTSD). Understanding the mechanisms of TMS action and developing biomarkers predicting response remain important goals. We applied a combination of machine learning and electroencephalography (EEG), testing whether machine learning analysis of EEG coherence would (1) predict clinical outcomes in individuals with comorbid MDD and PTSD, and (2) determine whether an individual had received a TMS course.

Methods: We collected resting-state 8-channel EEG before and after TMS (5 Hz to the left dorsolateral prefrontal cortex). We used Lasso regression and Support Vector Machine (SVM) to test the hypothesis that baseline EEG coherence predicted the outcome and to assess if EEG coherence changed after TMS.

Results: In our sample, clinical response to TMS were predictable based on pretreatment EEG coherence (n = 29). After treatment, 13/29 had more than 50% reduction in MDD self-report score 12/29 had more than 50% reduction in PTSD self-report score. For MDD, area under roc curve was for MDD was 0.83 (95% confidence interval 0.69-0.94) and for PTSD was 0.71 (95% confidence interval 0.54-0.87). SVM classifier was able to accurately assign EEG recordings to pre- and post-TMS treatment. The accuracy for Alpha, Beta, Theta and Delta bands was 75.4 ± 1.5%, 77.4 ± 1.4%, 73.8 ± 1.5%, and 78.6 ± 1.4%, respectively, all significantly better than chance (50%, p < 0.001).

Limitation: Limitations of this work include lack of sham condition, modest sample size, and a sparse electrode array. Despite these methodological limitations, we found validated and clinically meaningful results.

Conclusions: Machine learning successfully predicted non-response to TMS with high specificity, and identified pre- and post-TMS status using EEG coherence. This approach may provide mechanistic insights and may also become a clinically useful screening tool for TMS candidates.
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http://dx.doi.org/10.1016/j.jad.2019.03.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520189PMC
June 2019

Acute effects of aerobic exercise on negative affect and obsessions and compulsions in individuals with obsessive-compulsive disorder.

J Affect Disord 2019 02 14;245:991-997. Epub 2018 Nov 14.

University of Rhode Island, Department of Kinesiology, Kingston, RI USA.

Background: The acute effects of aerobic exercise on improved mood and anxiety reduction have been demonstrated across clinical and nonclinical populations. Limited work has evaluated the acute effects of aerobic exercise on negative affect, obsessions, and compulsions in patients with Obsessive Compulsive Disorder (OCD).

Method: Fifty-five patients (64% female) with treatment-resistant OCD were randomized to either 12 weeks of aerobic exercise (AE) or health education contact (HEC) control. Participants rated negative affect (i.e., mood and anxiety), obsessions and compulsions before and after each weekly AE or HEC session. Multilevel models were constructed to evaluate the effect of intervention condition, treatment week (time), and their interaction in terms of acute change in affect, obsession, and compulsions.

Results: Results reflected a main effect of condition, such that AE resulted in significantly larger increases in positive mood, and reductions in anxiety and compulsions, as compared to HEC. There was also a main effect of time in predicting acute anxiety reduction, such that linear reductions in anxiety over the course of treatment were observed. No significant effects were observed for acute changes in obsessions.

Limitations: The sample was small and was limited in demographic heterogeneity. Bouts of aerobic exercise were not standardized in terms of duration and mode, which could impact affective response to exercise, and acute affective OCD effects were exclusively self-reported.

Discussion: The current findings may help elucidate potential mechanisms of action of exercise on OCD outcomes. In addition, these results point toward the potential of designing exercise interventions that can teach patients to utilize individual bouts of physical activity, "in-the-moment" to improve mood and reduce anxiety and compulsions.
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http://dx.doi.org/10.1016/j.jad.2018.11.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037579PMC
February 2019

A Prospective Study of the Impact of Transcranial Alternating Current Stimulation on EEG Correlates of Somatosensory Perception.

Front Psychol 2018 20;9:2117. Epub 2018 Nov 20.

Department of Neuroscience, Brown University, Providence, RI, United States.

The (8-12 Hz) neocortical alpha rhythm is associated with shifts in attention across sensory systems, and is thought to represent a sensory gating mechanism for the inhibitory control of cortical processing. The present preliminary study sought to explore whether alpha frequency transcranial alternating current stimulation (tACS) could modulate endogenous alpha power in the somatosensory system, and whether the hypothesized modulation would causally impact perception of tactile stimuli at perceptual threshold. We combined electroencephalography (EEG) with simultaneous brief and intermittent tACS applied over primary somatosensory cortex at individuals' endogenous alpha frequency during a tactile detection task ( = 12 for EEG, = 20 for behavior). EEG-measured pre-stimulus alpha power was higher on non-perceived than perceived trials, and analogous perceptual correlates emerged in early components of the tactile evoked response. Further, baseline normalized tactile detection performance was significantly lower during alpha than sham tACS, but the effect did not last into the post-tACS time period. Pre- to post-tACS changes in alpha power were linearly dependent upon baseline state, such that alpha power tended to increase when pre-tACS alpha power was low, and decrease when it was high. However, these observations were comparable in both groups, and not associated with evidence of tACS-induced alpha power modulation. Nevertheless, the tactile stimulus evoked response potential (ERP) revealed a potentially lasting impact of alpha tACS on circuit dynamics. The post-tACS ERP was marked by the emergence of a prominent peak ∼70 ms post-stimulus, which was not discernible post-sham, or in either pre-stimulation condition. Computational neural modeling designed to simulate macroscale EEG signals supported the hypothesis that the emergence of this peak could reflect synaptic plasticity mechanisms induced by tACS. The primary lesson learned in this study, which commanded a small sample size, was that while our experimental paradigm provided some evidence of an influence of tACS on behavior and circuit dynamics, it was not sufficient to induce observable causal effects of tACS on EEG-measured alpha oscillations. We discuss limitations and suggest improvements that may help further delineate a causal influence of tACS on cortical dynamics and perception in future studies.
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http://dx.doi.org/10.3389/fpsyg.2018.02117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255923PMC
November 2018

Network Functional Architecture and Aberrant Functional Connectivity in Post-Traumatic Stress Disorder: A Clinical Application of Network Convergence.

Brain Connect 2018 11;8(9):549-557

1 Center for Neurorestoration and Neurotechnology, Providence VA Medical Center , Providence, Rhode Island.

Posttraumatic stress disorder (PTSD) is associated with disrupted functional connectivity in multiple neural networks. Multinetwork models of PTSD hypothesize that aberrant regional connectivity emerges from broad network-level disruptions. However, few studies have tested how characteristics of network-level organization influence regional functional connectivity in PTSD. This gap in knowledge impacts both our understanding of the pathophysiology of the disorder and the development of network-targeted PTSD treatments. We acquired resting-state imaging from a naturalistic sample of patients with PTSD (n = 42) and healthy controls (n = 42). Group differences in functional connectivity were identified using region of interest analyses and estimations of within- and between neural network activity; PTSD patients demonstrated reduced amygdala-orbitofrontal connectivity and increased default mode network (DMN) connectivity compared with controls. We then used convergence-a novel measure representing the capacity for functional integration-to test whether differences in functional architecture underlie connectivity signatures of PTSD. This approach found that reduced frontoparietal network (FPN) convergence was associated with reduced amygdala-orbitofrontal connectivity. Furthermore, in controls only, increased DMN convergence was associated with reduced DMN-to-salience network connectivity, and increased FPN convergence was associated with reduced FPN-to-ventral attention network connectivity. These results suggest that FPN functional architecture may underlie insufficiencies in top-down control in PTSD, with results broadly supporting the notion that networks' functional architecture influences the breakdown of normative functional relationships in PTSD. This work also indicates the potential of convergence to be applied to clinical populations in future research studies.
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http://dx.doi.org/10.1089/brain.2018.0634DOI Listing
November 2018

Transcranial Direct Current Stimulation for Affective Symptoms and Functioning in Chronic Low Back Pain: A Pilot Double-Blinded, Randomized, Placebo-Controlled Trial.

Pain Med 2019 06;20(6):1166-1177

Butler Hospital, Providence, Rhode Island.

Background And Objective: Chronic low back pain (CLBP) is highly prevalent, with a substantial psychosocial burden. Pain has both sensory and affective components. The latter component is a significant driver of disability and psychiatric comorbidity but is often inadequately treated. Previously we reported that noninvasive transcranial direct current stimulation (tDCS) may modulate pain-associated affective distress. Here we tested whether 10 daily tDCS sessions aimed to inhibit the left dorsal anterior cingulate cortex (dACC), a region strongly implicated in the affective component of pain, would produce selective reduction in pain-related symptoms.

Methods: In this multisite, double-blinded, randomized placebo-controlled trial (RCT), 21 CLBP patients received 10 weekday sessions of 2-mA active tDCS or sham (20 minutes/session). A cathodal electrode was placed over FC1 (10-20 electroencephalography coordinates), and an identical anodal return electrode was placed over the contralateral mastoid. Participants rated pain intensity, acceptance, interference, disability, and anxiety, plus general anxiety and depression.

Results: Regression analysis noted significantly less pain interference (P =0.002), pain disability (P =0.001), and depression symptoms (P =0.003) at six-week follow-up for active tDCS vs sham. Omnibus tests suggested that these improvements were not merely due to baseline (day 1) group differences.

Conclusions: To our knowledge, this is the first double-blinded RCT of multiple tDCS sessions targeting the left dACC to modulate CLBP's affective symptoms. Results are encouraging, including several possible tDCS-associated improvements. Better-powered RCTs are needed to confirm these effects. Future studies should also consider different stimulation schedules, additional cortical targets, high-density multi-electrode tDCS arrays, and multimodal approaches.
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http://dx.doi.org/10.1093/pm/pny188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544554PMC
June 2019

Combined transcranial direct current stimulation with virtual reality exposure for posttraumatic stress disorder: Feasibility and pilot results.

Brain Stimul 2019 Jan - Feb;12(1):41-43. Epub 2018 Sep 20.

Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI, 02908, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, 02906, USA.

Background: Facilitating neural activity using non-invasive brain stimulation may improve extinction-based treatments for posttraumatic stress disorder (PTSD).

Objective/hypothesis: Here, we examined the feasibility of simultaneous transcranial direct current stimulation (tDCS) application during virtual reality (VR) to reduce psychophysiological arousal and symptoms in Veterans with PTSD.

Methods: Twelve Veterans with PTSD received six combat-related VR exposure sessions during sham-controlled tDCS targeting ventromedial prefrontal cortex. Primary outcome measures were changes in skin conductance-based arousal and self-reported PTSD symptom severity.

Results: tDCS + VR components were combined without technical difficulty. We observed a significant interaction between reduction in arousal across sessions and tDCS group (p = .03), indicating that the decrease in physiological arousal was greater in the tDCS + VR versus sham group. We additionally observed a clinically meaningful reduction in PTSD symptom severity.

Conclusions: This study demonstrates feasibility of applying tDCS during VR. Preliminary data suggest a reduction in psychophysiological arousal and PTSD symptomatology, supporting future studies.
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http://dx.doi.org/10.1016/j.brs.2018.09.011DOI Listing
May 2019

Noninvasive Focused Ultrasound for Neuromodulation: A Review.

Psychiatr Clin North Am 2018 09 17;41(3):505-514. Epub 2018 Jul 17.

The Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02906, USA; Butler Hospital, 345 Blackstone Boulevard, Providence, RI 02906, USA; VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI 02908, USA.

This article covers noninvasive focused ultrasound (FUS) and its potential for neuromodulation. Although diagnostic uses of ultrasound are well known, its potential to noninvasively alter brain activity is a relatively new subject of research. Low-intensity focused ultrasound (LIFU) is a potential future alternative modality to other noninvasive neuromodulation techniques. This article aims at providing an updated review of the literature related to the role of LIFU in neuromodulation and the progress of animal as well as human research done on this topic. It also includes a critical review of the safety concerns slowing the translation of LIFU research into clinical trials.
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http://dx.doi.org/10.1016/j.psc.2018.04.010DOI Listing
September 2018

Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

Mol Psychiatry 2019 02 9;24(2):218-240. Epub 2018 May 9.

Discipline of Neurosurgery, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.
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http://dx.doi.org/10.1038/s41380-018-0054-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698394PMC
February 2019

5 Hz Repetitive transcranial magnetic stimulation for posttraumatic stress disorder comorbid with major depressive disorder.

J Affect Disord 2018 08 5;235:414-420. Epub 2018 Apr 5.

Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, United States; Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI, United States.

Background: Standard clinical protocols for repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) apply 10 Hz pulses over left prefrontal cortex, yet little is known about the effects of rTMS in more diagnostically complex depressed patients.

Objective/hypothesis: Posttraumatic stress disorder (PTSD) is commonly comorbid with MDD, and while rTMS has been shown to alleviate PTSD symptoms in preliminary studies, ideal parameters remain unclear. We conducted a prospective, open-label study of 5 Hz rTMS for patients with comorbid PTSD + MDD and hypothesized stimulation would reduce symptoms of both disorders.

Methods: Outpatients (N = 40) with PTSD + MDD and at least moderate global severity were enrolled. 5 Hz rTMS included up to 40 daily sessions followed by a 5-session taper. Symptoms were measured using the PTSD Checklist (PCL-5) and Inventory of Depressive Symptomatology, Self-Report (IDS-SR). Baseline-to-endpoint changes were analyzed.

Results: The intent-to-treat population included 35 participants. Stimulation significantly reduced PTSD symptoms (PCL-5 baseline mean ± SD score 52.2 ± 13.1 versus endpoint 34.0 ± 21.6; p < .001); 23 patients (48.6%) met a pre-defined categorical PTSD response criteria. MDD symptoms also improved significantly (IDS-SR, baseline 47.8 ± 11.9 to endpoint 30.9 ± 18.9; p < .001); 15 patients (42.9%) demonstrated categorical response and 12 (34.3%) remitted. PTSD and MDD symptom change was highly correlated (r = 0.91, p < .001).

Limitations: Unblinded single-arm study, with modest sample size.

Conclusion: Significant and clinically meaningful reductions in both MDD and PTSD symptoms were observed following stimulation. The preliminary efficacy of 5 Hz rTMS for both symptom domains in patients with comorbid disorders supports future controlled studies.
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http://dx.doi.org/10.1016/j.jad.2018.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567988PMC
August 2018

Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.

Biol Psychiatry 2018 09 15;84(5):355-364. Epub 2017 Dec 15.

Department of Stereotactic Neurosurgery, Cromwell Hospital, London, United Kingdom.

Background: Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD.

Methods: Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging.

Results: Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state.

Conclusions: Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.
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http://dx.doi.org/10.1016/j.biopsych.2017.11.034DOI Listing
September 2018

Self-reported executive function and hoarding in adults with obsessive-compulsive disorder.

Compr Psychiatry 2018 02 28;81:53-59. Epub 2017 Nov 28.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD.

Methods: The study sample included 431 adults diagnosed with DSM-IV OCD. Participants were assessed by clinicians for Axis I disorders, personality disorders, indecision, and hoarding. Executive functioning domains were evaluated using a self-report instrument, the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). We compared scores on these domains in the 143 hoarding and 288 non-hoarding participants, separately in men and women. We used logistic regression to evaluate relationships between executive function scores and hoarding, and correlation and linear regression analyses to evaluate relationships between executive function scores and hoarding severity, in women.

Results: In men, the hoarding group had a significantly higher mean score than the non-hoarding group only on the shift dimension. In contrast, in women, the hoarding group had higher mean scores on the shift scale and all metacognition dimensions, i.e., those that assess the ability to systematically solve problems via planning and organization. The relationships in women between hoarding and scores on initiating tasks, planning/organizing, organization of materials, and the metacognition index were independent of other clinical features. Furthermore, the severity of hoarding in women correlated most strongly with metacognition dimensions.

Conclusions: Self-reported deficits in planning and organization are associated with the occurrence and severity of hoarding in women, but not men, with OCD. This may have implications for elucidating the etiology of, and developing effective treatments for, hoarding in OCD.
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http://dx.doi.org/10.1016/j.comppsych.2017.11.009DOI Listing
February 2018