Peter Johannes van Roessel

All Publications

• Randomized waitlist-controlled trial of buried in treasures facilitated support groups and in-home uncluttering (BIT+) for hoarding disorder. Journal of psychiatric research Wheaton, M. G., Varias, A. D., Sandhu, T., Munoz Rodriguez, P. A., Mukunda, P., Filippou-Frye, M., Millen, A., Lombardi, A., van Roessel, P., Raila, H., Anderson, K., Linkovski, O., Mahnke, A., Sanchez, C., McCarthy, E., Wright, B., Mibenge, C., Rico, Y., Righi, S., Halsey, C., Torio, L., Asgari, S., Qiu, T., Garcia, G., Jo, B., Belofsky, B., Shuer, L. J., Frost, R. O., Rodriguez, C. I. 2024; 176: 58-67

  Abstract

  OBJECTIVE: The Buried in Treasures (BIT) workshop is a promising treatment for hoarding disorder (HD), though many participants struggle with home uncluttering. This randomized waitlist-controlled trial investigated the efficacy of a version of BIT, augmented with in-home uncluttering practice (BIT+).METHOD: Adults (N=41) with hoarding disorder were recruited from the community and randomly assigned to BIT+or waitlist. BIT+consisted of 16 sessions of the BIT workshop and 10 uncluttering home visits over 18 weeks. Outcome measures included the Saving Inventory-Revised (self-report) and the Clutter Image Rating Scale (self and independent evaluator rated). Between group repeated measures analyses using general linear modeling examined the effect of BIT+vs waitlist control on hoarding symptoms after 18 weeks. Within group analyses examined pre-post effects for all BIT+participants combined after 18 weeks.RESULTS: After 18 weeks, BIT+participants benefited significantly more than waitlist controls on hoarding severity with large effect size (Cohen's d=1.5, p<.001). BIT+ was also associated with improvement reductions in hoarding symptoms, clutter, and functional impairment.CONCLUSIONS: The BIT+intervention offers promise as a treatment option for hoarding. Adding in-home uncluttering practice may incrementally improve discarding practices. Future controlled trials are warranted.

  View details for DOI 10.1016/j.jpsychires.2024.05.055

  View details for PubMedID 38843580

• Neurocognitive Moderators of Group Psychotherapy Augmented by Individual Uncluttering Practice (BIT plus ) vs Waitlist Control van Roessel, P., Rodriguez, P., Jo, B., Williams, L., Rodriguez, C. ELSEVIER SCIENCE INC. 2024: S65

  View details for Web of Science ID 001282811900152

• Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans. Nature communications Hack, L. M., Zhang, X., Heifets, B. D., Suppes, T., van Roessel, P. J., Yesavage, J. A., Gray, N. J., Hilton, R., Bertrand, C., Rodriguez, C. I., Deisseroth, K., Knutson, B., Williams, L. M. 2023; 14 (1): 6631

  Abstract

  Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

  View details for DOI 10.1038/s41467-023-42141-5

  View details for PubMedID 37857620

  View details for PubMedCentralID 5126726

• Augmenting group hoarding disorder treatment with virtual reality discarding: A pilot study in older adults. Journal of psychiatric research Raila, H., Avanesyan, T., Valentine, K. E., Koo, B., Huang, C., Tsutsumi, Y., Andreeff, E., Qiu, T., Muñoz Rodríguez, P. A., Varias, A., Filippou-Frye, M., van Roessel, P., Bullock, K., Periyakoil, V. S., Rodríguez, C. I. 2023; 166: 25-31

  Abstract

  Hoarding disorder is common and debilitating, especially in older adults, and novel treatment approaches are needed. Many current treatments emphasize skills related to discarding and decision-making about possessions, which can be practiced in the patient's home. However in many cases, in-home visits are unfeasible, or real-life discarding is too difficult. Virtual reality (VR) offers the ability to create a virtual "home" including 3D scans of the patient's actual possessions that can be moved or discarded. VR discarding is an alternative to in-home visits and an approach that provides a stepping stone to real-life discarding. VR has been successfully utilized to treat many disorders but tested minimally in hoarding disorder. In nine older adults with hoarding disorder, we tested an 8-week VR intervention administered to augment a 16-week Buried in Treasures group treatment. Individualized VR rooms were uniquely modeled after each patient's home. During clinician-administered VR sessions, patients practiced sorting and discarding their virtual possessions. The intervention was feasible to administer. Open-ended participant responses, examined by two independent evaluators, indicated that VR sessions were well-tolerated and that participants found them useful, with nearly all participants noting that VR helped them increase real-life discarding. Self-reported hoarding symptoms decreased from baseline to close, with seven of the nine participants showing reliable improvement in this timeframe and none showing deterioration. Results from this exploratory pilot study suggest that VR is a feasible way to simulate an at-home sorting and discarding experience in a manner that may augment skills acquisition. It remains an open question whether VR discarding practice yields greater improvement than existing treatments. VR for this population merits further clinical investigation.

  View details for DOI 10.1016/j.jpsychires.2023.08.002

  View details for PubMedID 37716272

• Hoarding disorder: Questions and controversies JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS van Roessel, P., Rodriguez, P., Frost, R. O., Rodriguez, C. I. 2023; 37

  View details for DOI 10.1016/j.jocrd.2023.100808

  View details for Web of Science ID 001006891200001

• Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine Van Roessel, P., Asgari, S., Jo, B., Williams, L., Rodriguez, C. ELSEVIER SCIENCE INC. 2023: S311-S312

  View details for Web of Science ID 000993018500756

• Ketamine's Acute Effects on Negative Brain States are Mediated Through Distinct Altered States in Humans Zhang, X., Hack, L., Heifets, B., Suppes, T., Van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S312

  View details for Web of Science ID 000993018500757

• Acute Effects of MDMA on Negative Affective Brain Circuit Function: A Randomized Controlled Mechanistic Trial Hack, L., Zhang, X., Heifets, B., Suppes, T., van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S88

  View details for Web of Science ID 000993018500209

• Efficacy of Ketamine in Unmedicated Adults With OCD: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., van Roessel, P., DeBattista, C., Wintermark, M., Lombardi, A., Pinto, A., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. ELSEVIER SCIENCE INC. 2023: S83

  View details for Web of Science ID 000993018500200

• Acute Effects of MDMA on Intrinsic Functional Connectomes Associated With Altered States of Consciousness and Defensiveness Zhang, X., Hack, L., Heifets, B., Suppes, T., van Roessel, P., Yesavage, J., Gray, N., Hilton, R., Rodriguez, C., Deisseroth, K., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S87-S88

  View details for Web of Science ID 000993018500208

• Early life stress in adults with hoarding disorder: A mixed methods study JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS Sanchez, C., Linkovski, O., van Roessel, P., Steinberg, N., McCarthy, E., Rodriguez, P., Avanesyan, T., Mukunda, P., Frost, R. O., Rodriguez, C. I. 2023; 37

  View details for DOI 10.1016/j.jocrd.2023.100785

  View details for Web of Science ID 000948662100001

• Augmenting group hoarding disorder treatment with virtual reality discarding: A pilot study in older adults Augmenting group hoarding disorder treatment with virtual reality discarding: A pilot study in older adults Raila, H. 2023

  View details for DOI 10.1016/j.jpsychires.2023.08.002

• Anosognosia in hoarding disorder is predicted by alterations in cognitive and inhibitory control. Scientific reports van Roessel, P. J., Marzke, C., Varias, A. D., Mukunda, P., Asgari, S., Sanchez, C., Shen, H., Jo, B., Gunaydin, L. A., Williams, L. M., Rodriguez, C. I. 2022; 12 (1): 21752

  Abstract

  Insight impairment contributes significantly to morbidity in psychiatric disorders. The neurologic concept of anosognosia, reflecting deficits in metacognitive awareness of illness, is increasingly understood as relevant to psychopathology, but has been little explored in psychiatric disorders other than schizophrenia. We explored anosognosia as an aspect of insight impairment in n = 71 individuals with DSM-5 hoarding disorder. We used a standardized clutter severity measure to assess whether individuals with hoarding disorder underreport home clutter levels relative to independent examiners. We then explored whether underreporting, as a proxy for anosognosia, is predicted by clinical or neurocognitive behavioral measures. We found that individuals with hoarding disorder underreport their clutter, and that underreporting is predicted by objective severity of clutter. In an n = 53 subset of participants, we found that underreporting is predicted by altered performance on tests of cognitive control and inhibition, specifically Go/No-Go and Stroop tests. The relation of underreporting to objective clutter, the cardinal symptom of hoarding disorder, suggests that anosognosia may reflect core pathophysiology of the disorder. The neurocognitive predictors of clutter underreporting suggest that anosognosia in hoarding disorder shares a neural basis with metacognitive awareness deficits in other neuropsychiatric disorders and that executive anosognosia may be a transdiagnostic manifestation of psychopathology.

  View details for DOI 10.1038/s41598-022-25532-4

  View details for PubMedID 36526652

• Identity gripping or identity flight? Two distinct experiences correlated with self-reported depression in retired professional ice hockey players INTERNATIONAL JOURNAL OF SPORT AND EXERCISE PSYCHOLOGY Aston, P. R., Brewer, M. A., Kieschnick, D. W., Allen, M. C., van Roessel, P. J., Lavallee, D. E., Rodriguez, C. I. 2022

  View details for DOI 10.1080/1612197X.2022.2152853

  View details for Web of Science ID 000893569700001

• Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine van Roessel, P., Asgari, S., Jo, B., Williams, L., Rodriguez, C. SPRINGERNATURE. 2022: 302

  View details for Web of Science ID 000929613800573

• Efficacy of Ketamine in Unmedicated Adults With Obsessive-Compulsive Disorder: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., van Roessel, P., DeBattista, C., Flood, P., Ringold, A., Wintermark, M., Anderson, K., Linkovski, O., Lombardi, A., Millen, A., Pinto, A., Raila, H., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. SPRINGERNATURE. 2022: 302-303

  View details for Web of Science ID 000897934700574

• Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine van Roessel, P., Asgari, S., Jo, B., Williams, L., Rodriguez, C. SPRINGERNATURE. 2022: 302

  View details for Web of Science ID 000897934700573

• Efficacy of Ketamine in Unmedicated Adults With Obsessive-Compulsive Disorder: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., Van Roessel, P., DeBattista, C., Flood, P., Ringold, A., Wintermark, M., Anderson, K., Linkovski, O., Lombardi, A., Millen, A., Pinto, A., Raila, H., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. SPRINGERNATURE. 2022: 302-303

  View details for Web of Science ID 000929613800574

• Treatment-resistant OCD: Pharmacotherapies in adults. Comprehensive psychiatry van Roessel, P. J., Grassi, G., Aboujaoude, E. N., Menchon, J. M., Van Ameringen, M., Rodriguez, C. I. 2022; 120: 152352

  Abstract

  Serotonin reuptake inhibitor (SRI) medications are well established as first-line pharmacotherapeutic treatment for Obsessive-Compulsive Disorder (OCD). However, despite the excellent safety profile and demonstrated efficacy of these medications, a substantial proportion of individuals with OCD fail to attain sufficient benefit from SRIs. In this narrative review, we discuss clinical features of OCD that have been associated with poorer response to SRIs, and we present pharmacotherapeutic interventions that have been explored as augmenting or alternative treatments for treatment-resistant OCD. We additionally highlight non-SRI interventions for OCD that are currently under investigation. Pharmacotherapeutic interventions were identified via expert consensus. To assess the evidence base for individual pharmacotherapies, targeted searches for relevant English-language publications were performed on standard biomedical research databases, including MEDLINE. Information relevant to ongoing registered clinical trials in OCD was obtained by search of ClinicalTrials.gov. Pharmacotherapies are grouped for review in accordance with the general principles of Neuroscience-based Nomenclature (NbN). Clinical features of OCD that may suggest poorer response to SRI treatment include early age of onset, severity of illness, duration of untreated illness, and the presence of symmetry/ordering or hoarding-related symptoms. Based on evolving pathophysiologic models of OCD, diverse agents engaging serotonin, dopamine, norepinephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Medications with dopamine antagonist activity remain the most robustly evidence-based of augmenting interventions, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Interventions targeting glutamatergic and anti-inflammatory pathways are less well evidenced, but may offer more favorable benefit to risk profiles. Ongoing research should explore whether specific interventions may benefit individuals with particular features of treatment-resistant OCD.

  View details for DOI 10.1016/j.comppsych.2022.152352

  View details for PubMedID 36368186

• Valence processing alterations in SAPAP3 knockout mice and human OCD. Journal of psychiatric research Kajs, B. L., van Roessel, P. J., Davis, G. L., Williams, L. M., Rodriguez, C. I., Gunaydin, L. A. 2022; 151: 657-666

  Abstract

  Abnormalities in valence processing - the processing of aversive or appetitive stimuli - may be an underrecognized component of obsessive-compulsive disorder (OCD). Preclinical rodent models have been critical in furthering pathophysiological understanding of OCD, yet there is a dearth of investigations examining whether rodent models of compulsive behavior show alterations in valence systems congruent with those seen in individuals with OCD. In this study, we sought to assess valence processing in a preclinical rodent model of compulsive behavior, the SAPAP3 knockout (KO) mouse model, and compare our preclinical findings to similar behavioral phenomena in OCD patients. In SAPAP3 KO mice, we used auditory fear conditioning and extinction to examine alterations in negative valence processing and reward-based operant conditioning to examine alterations in positive valence processing. We find that SAPAP3 KO mice show evidence of heightened negative valence processing through enhanced fear learning and impaired fear extinction. SAPAP3 KO mice also show deficits in reward acquisition and goal-directed behavior, suggesting impaired positive valence processing. In OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence). We find similar trends towards enhanced negative and impaired positive valence processing in OCD patients. Overall, our results reveal valence processing abnormalities in a preclinical rodent model of compulsive behavior similar to those seen in OCD patients, with implications for valence processing alterations as novel therapeutic targets across a translational research spectrum.

  View details for DOI 10.1016/j.jpsychires.2022.05.024

  View details for PubMedID 35661523

• Deconstructing Ketamine-Induced Changes in Cortisol and Dissociative and Affective States in a Controlled Mechanistic Study Hack, L. M., Zhang, X., Brawer, J., Gray, N., Heifets, B., Suppes, T., van Roessel, P., Rodriguez, C., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2022: S178-S179

  View details for Web of Science ID 000789022200436

• Acute Ketamine Modulates Cognitive Control Network Activity During Cognitive Inhibition: Evidence From a Mechanistic Trial Zhang, X., Hack, L., Brawer, J., Gray, N., Heifets, B., Suppes, T., van Roessel, P., Rodriguez, C., Knutson, B., Williams, L. ELSEVIER SCIENCE INC. 2022: S225

  View details for Web of Science ID 000789022200552

• Accelerated Neuromodulation Therapy for Obsessive-Compulsive Disorder. Brain stimulation Williams, N. R., Sudheimer, K. D., Cole, E. J., Varias, A. D., Goldstein-Piekarski, A. N., Stetz, P. n., Lombardi, A. n., Filippou-Frye, M. n., van Roessel, P. n., Anderson, K. n., McCarthy, E. A., Wright, B. n., Sandhu, T. n., Menon, S. n., Jo, B. n., Koran, L. n., Williams, L. M., Rodriguez, C. I. 2021

  Abstract

  The open-label trial of Williams, Sudheimer, Cole, et al., suggests safety, feasibility, and high efficacy for treatment-refractory OCD of an accelerated, fMRI-guided, high-dose, cTBSmod protocol targeting the right frontal pole. Larger, randomized, controlled trials are needed to test the promising results of this pilot study. CLINICALTRIALS.GOV REGISTRY NUMBERS: NCT03404609.

  View details for DOI 10.1016/j.brs.2021.02.013

  View details for PubMedID 33631349

• Examining subjective sleep quality in adults with hoarding disorder. Journal of psychiatric research Mahnke, A. R., Linkovski, O., Timpano, K., van Roessel, P., Sanchez, C., Varias, A. D., Mukunda, P., Filippou-Frye, M., Lombardi, A., Raila, H., Anderson, K., Sandhu, T., Wright, B., McCarthy, E. A., Garcia, G. E., Asgari, S., Qiu, T., Bernert, R., Rodriguez, C. I. 2020

  Abstract

  Hoarding disorder (HD), characterized by difficulty parting with possessions and functionally impairing clutter, affects 2-6% of the population. Originally considered part of Obsessive-Compulsive Disorder (OCD), HD became a distinct diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. While sleep impacts OCD, little is known about sleep in HD. As HD patients often report poor sleep in clinical settings, understanding global subjective sleep quality and disturbances may lead to novel therapeutic targets. To address this gap, the authors used a sample of convenience: an existing data set designed to screen research study eligibility and explore the psychopathology and phenomenology of OCD and HD. The data set included information collected from individuals with HD (n=38), OCD (n=26), and healthy participants (n=22) about insomnia, sleep quality, and mood using interviews and structured instruments including the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Depression Anxiety Stress Scales (DASS). In this data set, HD and OCD groups reported significantly greater insomnia symptoms and poorer sleep quality compared with healthy controls while controlling for depression, age, and gender. A sizable minority of HD and OCD individuals met criteria for comorbid sleep disorders. OCD and HD groups differed in delayed sleep phase prevalence. To our knowledge, this is the first study examining subjective sleep quality and insomnia in HD as compared to healthy individuals and those with OCD, while controlling for relevant clinical characteristics. Given that there are evidence-based treatments for insomnia and other sleep disorders, our study raises the possibility that treatment interventions targeting sleep may improve HD outcomes.

  View details for DOI 10.1016/j.jpsychires.2020.10.044

  View details for PubMedID 33309063

• Self-Reported Depressive Symptoms in Active and Retired Professional Hockey Players CANADIAN JOURNAL OF BEHAVIOURAL SCIENCE-REVUE CANADIENNE DES SCIENCES DU COMPORTEMENT Aston, P., Filippou-Frye, M., Blasey, C., van Roessel, P., Rodriguez, C. 2020; 52 (2): 97–106

  View details for DOI 10.1037/cbs0000169

  View details for Web of Science ID 000522152100002

• Does Nitrous Oxide Help Veterans With Posttraumatic Stress Disorder? A Case Series. The Journal of clinical psychiatry Varias, A. n., van Roessel, P. n., Parsiani, M. n., Filippou-Frye, M. n., Neylan, T. C., Nagele, P. n., Yesavage, J. n., Clark, J. D., Rodriguez, C. I. 2020; 81 (4)

  View details for DOI 10.4088/JCP.20l13393

  View details for PubMedID 32609959

• Neurocognitive Correlates of Insight in Hoarding Disorder van Roessel, P., Varias, A., Sanchez, C., Sandhu, T., Shen, H., Jo, B., Rodriguez, C. NATURE PUBLISHING GROUP. 2019: 159

  View details for Web of Science ID 000509665600307

• Exploring Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Extinction Learning-Based Treatment Outcome in Obsessive-Compulsive Disorder A Pilot Study JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Linkovski, O., Wheaton, M. G., Zwerling, J., Odgerel, Z., van Roessel, P., Filippou-Frye, M., Lombardi, A., Wright, B., Steinman, S. A., Simpson, H., Lee, F., Rodriguez, C. I. 2019; 39 (1): 91–93

  View details for DOI 10.1097/JCP.0000000000000994

  View details for Web of Science ID 000455489200020

• Exploring Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Extinction Learning-Based Treatment Outcome in Obsessive-Compulsive Disorder: A Pilot Study. Journal of clinical psychopharmacology Linkovski, O., Wheaton, M. G., Zwerling, J., Odgerel, Z., van Roessel, P., Filippou-Frye, M., Lombardi, A., Wright, B., Steinman, S. A., Simpson, H. B., Lee, F., Rodriguez, C. I. 2018

  View details for PubMedID 30531475

• Clutter Blindness as an Insight Proxy in Hoarding Disorder: A Hypothesis-Generating Study van Roessel, P., Sanchez, C., Linkovski, O., Sandhu, T., Wright, B., McCarthy, E., Varias, A., Filippou-Frye, M., Shen, H., Jo, B., Rodriguez, C. NATURE PUBLISHING GROUP. 2018: S387–S388

  View details for Web of Science ID 000509546600710

• Exploring BDNF Val66Met Polymorphism and Extinction Learning-Based Treatment Outcome in OCD: A Pilot Study Linkovski, O., Wheaton, M., Zwerling, J., Oderel, Z., van Roessel, P., Filippou, M., Lombardi, A., Wright, B., Steinman, S., Simpson, H., Lee, F., Rodriguez, C. NATURE PUBLISHING GROUP. 2018: S387

  View details for Web of Science ID 000509546600709

• A Role for Dystonia-Associated Genes in Spinal GABAergic Interneuron Circuitry. Cell reports Zhang, J. n., Weinrich, J. A., Russ, J. B., Comer, J. D., Bommareddy, P. K., DiCasoli, R. J., Wright, C. V., Li, Y. n., van Roessel, P. J., Kaltschmidt, J. A. 2017; 21 (3): 666–78

  Abstract

  Spinal interneurons are critical modulators of motor circuit function. In the dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits proprioceptive sensory afferent terminals, thus negatively regulating sensory-motor signaling. Although deficits in presynaptic inhibition have been inferred in human motor diseases, including dystonia, it remains unclear whether GABApre circuit components are altered in these conditions. Here, we use developmental timing to show that GABApre neurons are a late Ptf1a-expressing subclass and localize to the intermediate spinal cord. Using a microarray screen to identify genes expressed in this intermediate population, we find the kelch-like family member Klhl14, implicated in dystonia through its direct binding with torsion-dystonia-related protein Tor1a. Furthermore, in Tor1a mutant mice in which Klhl14 and Tor1a binding is disrupted, formation of GABApre sensory afferent synapses is impaired. Our findings suggest a potential contribution of GABApre neurons to the deficits in presynaptic inhibition observed in dystonia.

  View details for PubMedID 29045835

• Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord NEURON Mende, M., Fletcher, E. V., Belluardo, J. L., Pierce, J. P., Bommareddy, P. K., Weinrich, J. A., Kabir, Z. D., Schierberl, K. C., Pagiazitis, J. G., Mendelsohn, A. I., Francesconi, A., Edwards, R. H., Milner, T. A., Rajadhyaksha, A. M., van Roessel, P. J., Mentis, G. Z., Kaltschmidt, J. A. 2016; 90 (6): 1189-1202

  Abstract

  Circuit function in the CNS relies on the balanced interplay of excitatory and inhibitory synaptic signaling. How neuronal activity influences synaptic differentiation to maintain such balance remains unclear. In the mouse spinal cord, a population of GABAergic interneurons, GABApre, forms synapses with the terminals of proprioceptive sensory neurons and controls information transfer at sensory-motor connections through presynaptic inhibition. We show that reducing sensory glutamate release results in decreased expression of GABA-synthesizing enzymes GAD65 and GAD67 in GABApre terminals and decreased presynaptic inhibition. Glutamate directs GAD67 expression via the metabotropic glutamate receptor mGluR1β on GABApre terminals and regulates GAD65 expression via autocrine influence on sensory terminal BDNF. We demonstrate that dual retrograde signals from sensory terminals operate hierarchically to direct the molecular differentiation of GABApre terminals and the efficacy of presynaptic inhibition. These retrograde signals comprise a feedback mechanism by which excitatory sensory activity drives GABAergic inhibition to maintain circuit homeostasis.

  View details for DOI 10.1016/j.neuron.2016.05.008

  View details for PubMedID 27263971

• Care within a Veterans Hospital - Earlier detection of colon cancer SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES van Roessel, P., Rouse, R. V., Wren, S. M. 2007; 21 (8): 1434-1440

  Abstract

  In 1998 the Veterans Administration mandated an externally monitored targeted colon cancer screening rate that was expected to result in earlier cancer detection and improved patient survival. The effectiveness of the protocol was evaluated in a retrospective case series at a tertiary care Veterans Administration Hospital that included all patients with the diagnosis of colon cancer between 1991 and 2003.Tumor stage, tumor location, and patient survival data were recorded and compared to National Cancer Data Base (NCDB) benchmarks.The study facility had a greater percentage of early cancers and fewer later stage cancers than the NCDB benchmark. Overall survival was better for the VA cohort compared to NCDB (all-cause 5-year survival: VA, 0.72; NCDB, 0.47. p < or = .001).The VA facility had a significantly greater percentage of early cancers and fewer stage III or IV cancers compared to a national benchmark and significantly improved survival compared to the national benchmark.

  View details for DOI 10.1007/s00464-006-9184-6

  View details for PubMedID 17294311

• Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell van Roessel, P. n., Elliott, D. A., Robinson, I. M., Prokop, A. n., Brand, A. H. 2004; 119 (5): 707–18

  Abstract

  Neuronal plasticity relies on tightly regulated control of protein levels at synapses. One mechanism to control protein abundance is the ubiquitin-proteasome degradation system. Recent studies have implicated ubiquitin-mediated protein degradation in synaptic development, function, and plasticity, but little is known about the regulatory mechanisms controlling ubiquitylation in neurons. In contrast, ubiquitylation has long been studied as a central regulator of the eukaryotic cell cycle. A critical mediator of cell-cycle transitions, the anaphase-promoting complex/cyclosome (APC/C), is an E3 ubiquitin ligase. Although the APC/C has been detected in several differentiated cell types, a functional role for the complex in postmitotic cells has been elusive. We describe a novel postmitotic role for the APC/C at Drosophila neuromuscular synapses: independent regulation of synaptic growth and synaptic transmission. In neurons, the APC/C controls synaptic size via a downstream effector Liprin-alpha; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor.

  View details for PubMedID 15550251

• Spreading silence with Sid. Genome biology van Roessel, P. n., Brand, A. H. 2004; 5 (2): 208

  Abstract

  RNA interference (RNAi) has been shown to spread from cell to cell in plants and in Caenorhabditis elegans, but it does not spread in other organisms, such as Drosophila. A recent report demonstrates that a membrane channel, encoded by the gene sid-1, is responsible for the spreading of RNAi between cells.

  View details for PubMedID 14759251

• Region-specific apoptosis limits neural stem cell proliferation. Neuron Brand, A. H., van Roessel, P. J. 2003; 37 (2): 185–87

  Abstract

  Regulation of stem cell division is of particular interest, both for studies of development and for stem cell therapeutics. In this issue of Neuron, Bello et al. show that the number of divisions of Drosophila neural stem cells is limited, in a region-specific manner, by regulated apoptosis in response to a pulse of expression of the Hox gene abdominal-A (abdA).

  View details for PubMedID 12546811

• Imaging into the future: visualizing gene expression and protein interactions with fluorescent proteins. Nature cell biology van Roessel, P. n., Brand, A. H. 2002; 4 (1): E15–20

  Abstract

  Since its introduction into heterologous organisms as a marker of gene expression, the green fluorescent protein (GFP) has led a dramatic revolution in cell, developmental and neurobiology. By allowing breathtaking visualization of fluorescent fusion proteins as they move within and between cells, GFP has fundamentally transformed the spatial analysis of protein function. Now, new GFP technologies allow far more than simple observations of fusion protein localization. The growing family of fluorescent protein variants is enabling more sophisticated studies of protein function and illuminating wide-ranging processes from gene expression to second-messenger cascades and intercellular signalling. Together with advances in microscopy, new GFP-based experimental approaches are forging a second GFP revolution.

  View details for PubMedID 11780139

• Two-color GFP imaging demonstrates cell-autonomy of GAL4-driven RNA interference in Drosophila. Genesis van Roessel, P. J., Hayward, N. M., Barros, C. S., Brand, A. H. 2002; 34 (1-2): 4

  View details for DOI 10.1002/gene.10146

• Activity of long-wavelength cones under scotopic conditions in the cyprinid fish Danio aequipinnatus. Journal of comparative physiology. A, Sensory, neural, and behavioral physiology van Roessel, P., Palacios, A. G., Goldsmith, T. H. 1997; 181 (5): 493-500

  Abstract

  In carp (Cyprinus) and goldfish (Carassius), long-wavelength cones are reported to be active under scotopic conditions. Using the electroretinogram (ERG), we tested another cyprinid fish, Danio aequipinnatus, which contains A1-based visual pigments and for which we had previously measured the spectral sensitivities of individual cones. Dark adaptation curves show a rod/cone break at about 45 min. When thoroughly dark-adapted, the spectral sensitivity function is broader than can be accounted for by self-screening of rhodopsin, but it can be modeled by an additive combination of rods and the 560-nm cones. Dim, red background light causes adaptation of rods and a broadening of the spectral sensitivity function, which can be simulated by increasing the proportion of cones in the model. Brighter red backgrounds adapt the 560-nm cones. Because of the effect of red adapting lights, the ERG evidence for the participation of long-wavelength cones close to visual threshold appears to be different in Danio than in the goldfish Carassius.

  View details for PubMedID 9373956