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Cited by 250Obsessive-Compulsive Spectrum DisordersAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesPsychoanalysis and Psychopathology Research

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

Open access
Shephard, Elizabeth, Stern, Emily R., van den Heuvel, Odile A., Costa, Daniel L. C., Batistuzzo, Marcelo C., Godoy, Priscilla B. G., Lopes, Antonio C., Brunoni, Andre R. +7 more·2021·Molecular Psychiatry
DOI 10.1038/s41380-020-01007-8PMC PMC8260628
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Abstract

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

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Crossref · 10.1038/s41380-020-01007-8

Cites

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  • Premisecitation

    Some patients have no obsessions but perform rituals to obtain specific tactile, visual, or auditory sensations, a sense of completeness, or a just-right feeling, known as sensory phenomena.

    “In addition, some patients do not have obsessions but perform their rituals to relieve or achieve specific tactile, visual or auditory sensations, a sense of completeness or a just-right feeling (i.e., sensory phenomena [22]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Miguel EC, Prado HS, Rauch SL, Coffey BJ, Baer L, Savage CR, et al. Sensory phenomena in obsessive-compulsive disorder and Tourette’s disorder. J Clin Psychiatry. 2000;61:150–6. source

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  • Interpretationcitation

    Impaired safety-signaling functions of the vmPFC likely contribute to difficulty extinguishing learned fear in OCD.

    “likely due to impaired “safety-signaling” functions of the vmPFC [40], which may further contribute to the maintenance of fear-related OCD symptoms.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Apergis-Schoute AM, Gillan CM, Fineberg NA, Fernandez-Egea E, Sahakian BJ, Robbins TW. Neural basis of impaired safety signaling in obsessive compulsive disorder. PNAS. 2017;114:3216–21. source

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  • Premisecitation

    Some patients perform compulsive behaviors because they feel rewarding or almost pleasurable, not to obtain relief.

    “Some patients carry out compulsive behaviors because they feel rewarding and almost pleasurable, rather than to elicit a sense of relief [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Ferreira GM, Yücel M, Dawson A, Lorenzetti V, Fontenelle LF. Investigating the role of anticipatory reward and habit strength in obsessive-compulsive disorder. CNS Spectr. 2017;22:295–304. source

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  • Premisecitation

    Clusters of individuals with neural network alterations have been identified in depression, psychotic disorders, and ADHD.

    “Indeed, clusters of individuals with neural network alterations have been identified in depression [7–8], psychotic disorders [9] and attention-deficit/hyperactivity disorder (ADHD [10]).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [7] Williams LM. Precision psychiatry: a neural circuit taxonomy for depression and anxiety. Lancet Psychiatry. 2016;3:472–80. source

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    • cites [8] Wager TD, Woo CW. Imaging biomarkers and biotypes for depression. Nat Med. 2017;23:16–17. https://doi.org/10.1038/nm.4264. source

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    • cites [9] Clementz BA, Sweeney JA, Hamm JP, Ivleva EI, Ethridge LE, Pearlson GD, et al. Identification of distinct psychosis biotypes using brain-based biomarkers. Am J Psychiatry. 2016;173:373–84. source

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    • cites [10] Barth B, Mayer-Carius K, Strehl U, Kelava A, Häußinger FB, Fallgatter AJ, et al. Identification of neurophysiological biotypes in attention deficit hyperactivity disorder. Psychiatry Clin Neurosci. 2018;72:836–48. source

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  • Premisecitation

    Intolerance of uncertainty predicts impaired fear extinction in non-psychiatric volunteers.

    “Interestingly, IU has been shown to predict impaired fear extinction in non-psychiatric volunteers [48]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Morriss J, Christakou A, van Reekum CM. Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry. Biol Mood Anxiety Disord. 2015;5:4. source

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  • May combine two claims. 50
  • Classified as probably not a substantial claim. 11

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    Interpretationreasoning

    Individuals with OCD may differ in the degree and pattern of alterations across these neurocircuits, which could lead to phenotypic heterogeneity.

    “Therefore, individuals with OCD may have different degrees and patterns of alterations in these neurocircuits, leading to the phenotypic heterogeneity.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Neuroimaging studies have reported increased amygdala activity, reduced dorsal prefrontal activity, and reduced prefrontal-amygdala functional connectivity during provocation and cognitive reappraisal of OCD-provoking stimuli.

    “Consistent with these clinical observations, neuroimaging studies have reported increased amygdala activity, reduced dorsal prefrontal activity and reduced prefrontal-amygdala functional connectivity during the provocation and cognitive reappraisal of stimuli that provoke OCD symptoms and increase physiological arousal [36, 39].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:563–71.

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    • cites [39] Paul S, Beucke JC, Kaufmann C, Mersov A, Heinzel S, Kathmann N, et al. Amygdala–prefrontal connectivity during appraisal of symptom-related stimuli in obsessive–compulsive disorder. Psychol Med. 2019;49:278–86. source

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    Interpretationreasoning

    Distinct neurocircuit alterations could help explain heterogeneity across mental disorders, and interventions targeting specific circuit dysfunctions could improve treatment efficacy and guide clinical practice.

    “Distinct neurocircuit alterations could help explain the heterogeneity of mental disorders, and targeted interventions focused on specific circuit dysfunctions could improve treatment efficacy and guide clinical practice.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Current diagnostic classification systems allow clinicians to communicate diagnoses but are largely etiologically agnostic about the biological nature of psychopathology.

    “Current diagnostic classification systems [1–2] are effective in ensuring communication of diagnoses among clinicians but are largely “etiologically agnostic” when determining the biological nature of psychopathology [3].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Association; Arlington, VA 2013. source

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    • cites [2] World Health Organization. The ICD-10 classification of mental and behavioural disorders: diagnostic criteria for research. World Health Organization; Geneva, Switzerland 1993.

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    • cites [3] Cuthbert BN, Insel TR. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med. 2013;11:126. source

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    Premisecitation

    High psychiatric comorbidity and heterogeneity, fluid symptom trajectories, cross-diagnostic overlap in genetic and neurobiological factors, and limited efficacy of many psychiatric treatments restrict understanding the neurobiology of mental illness through categorical diagnoses.

    “High levels of psychiatric comorbidity and heterogeneity, fluid symptom trajectories, cross-diagnostic overlap in genetic and neurobiological factors, and the limited efficacy of many psychiatric treatments restrict our understanding of the neurobiology of mental illness based on categorical diagnoses [3–6].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [3] Cuthbert BN, Insel TR. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med. 2013;11:126. source

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    • cites [4] Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013;381:1371–9. source

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    • cites [5] van den Heuvel MP, Sporns O. A cross-disorder connectome landscape of brain dysconnectivity. Nat Rev Neurosci. 2019;20:435–46. source

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    • cites [6] Wang T, Zhang X, Li A, Zhu M, Liu S, Qin W, et al. Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations. NeuroImage: Clin. 2017;14:441–9. source

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    Premisecitation

    OCD has traditionally been linked to dysfunctional cortico-striatal-thalamo-cortical circuits, but alterations in fronto-limbic, fronto-parietal, and cerebellar circuits also contribute.

    “OCD has traditionally been associated with dysfunctional cortico-striatal-thalamo-cortical (CSTC) circuits [12–13], although it is now recognized that alterations in other circuits (fronto-limbic, fronto-parietal, cerebellar) also play a role [14].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000;28:343–7. source

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    • cites [13] Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43–51. source

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    • cites [14] Stein DJ, Costa DLC, Lochner C, Miguel EC, Reddy YCJ, Shavitt RG, et al. Obsessive–compulsive disorder. Nat Rev Dis Primers. 2019;5:1–26. source

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    Premisecitation

    Neuroimaging studies have reported increased vmPFC and amygdala activity during anticipation of uncertain threat and during uncertainty in decision-making in OCD patients.

    “Importantly, neuroimaging studies have reported atypically increased vmPFC and amygdala activity during the anticipation of uncertain threat [46] and during uncertainty in decision-making [47] in OCD patients, suggestive of fronto-limbic hyper-responsivity to uncertainty in OCD.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [46] Weidt S, Lutz J, Rufer M, Delsignore A, Jakob NJ, Herwig U, et al. Common and differential alterations of general emotion processing in obsessive-compulsive and social anxiety disorder. Psychol Med. 2016;46:1427–36. source

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    • cites [47] Stern ER, Welsh RC, Gonzalez R, Fitzgerald KD, Abelson JL, Taylor SF. Subjective uncertainty and limbic hyperactivation in obsessive‐compulsive disorder. Hum Brain Mapp. 2013;34:1956–70. source

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    Interpretationcitation

    Hyperactive limbic fear responses and insufficient dorsal prefrontal top-down control are involved in producing or maintaining fear in response to OCD triggers.

    “Together, these findings suggest that hyperactive limbic fear responses and insufficient recruitment of dorsal prefrontal top-down control are involved in the production and/or maintenance of fear in the context of OCD triggers.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Dysregulated fear mediated by fronto-limbic circuitry has been proposed as a key mechanism in OCD.

    “First, dysregulated fear, i.e. excessive and/or poorly controlled fear responses mediated by fronto-limbic circuitry, has been proposed as a key mechanism in OCD [37]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, et al. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry. 2013;70:608–18. source

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    Premisecitation

    It remains unclear how phenotypic subtypes of OCD relate to specific pathophysiological mechanisms or whether they help guide treatment selection.

    “However, it remains unclear how these different phenotypic subtypes are associated with specific pathophysiological mechanisms or their usefulness in guiding treatment selection [21].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Miguel EC, Leckman JF, Rauch S, do Rosario-Campos MC, Hounie AG, Mercadante MT, et al. Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry. 2005;10:258–75. source

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    Premisecitation

    SSRIs reduce fronto-limbic responses to threatening stimuli in non-psychiatric volunteers and are associated with lower limbic response during emotion processing and symptom provocation in OCD.

    “there is evidence that selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for OCD [13], reduce fronto-limbic responses to threatening stimuli in non-psychiatric volunteers [56, but see 57] and are associated with lower limbic response during emotion processing and symptom provocation in OCD [36].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [56, but see 57]

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    • cites [36] Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:563–71.

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    Premisecitation

    fMRI neurofeedback targeting orbitofrontal regions correlated with contamination anxiety reduced connectivity between those regions and limbic areas including the amygdala and increased connectivity in prefrontal emotion-regulation regions.

    “resulted in significantly reduced connectivity between the orbitofrontal regions and other limbic areas, including the amygdala, as well as significantly increased connectivity in prefrontal regions associated with emotion regulation, including right lateral PFC [64].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Scheinost D, Stoica T, Saksa J, Papademetris X, Constable RT, Pittenger C, et al. Orbitofrontal cortex neurofeedback produces lasting changes in contamination anxiety and resting-state connectivity. Transl Psychiatry. 2013;3:e250. source

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    Premisecitation

    ERP appears to be mediated at least partly by modulation of amygdala-vmPFC connectivity, while cognitive reappraisal dampens fronto-limbic activity through top-down dorsal prefrontal regions.

    “ERP seems to be mediated, at least in part, by modulation of amygdala-vmPFC connectivity, while cognitive reappraisal appears to dampen fronto-limbic activity via the engagement of top-down dorsal prefrontal regions [35–36, 39, 51].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [35] Kohn N, Eickhoff SB, Scheller M, Laird AR, Fox PT, Habel U. Neural network of cognitive emotion regulation - an ALE meta-analysis and MACM analysis. Neuroimage. 2014;87:345–55. source

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    • cites [36] Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:563–71.

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    • cites [39] Paul S, Beucke JC, Kaufmann C, Mersov A, Heinzel S, Kathmann N, et al. Amygdala–prefrontal connectivity during appraisal of symptom-related stimuli in obsessive–compulsive disorder. Psychol Med. 2019;49:278–86. source

      Not checked in the free run.

    • cites [51] Buhle JT, Silvers AJ, Wager TD, Lopez R, Onyemekwu C, Kober H. Cognitive Reappraisal of Emotion: A meta-analysis of human neuroimaging studies. Cereb Cortex. 2014;24:2981–90. source

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  • May combine two claims.

    Interpretationreasoning

    CBT may target fronto-limbic dysfunction directly through ERP or indirectly through cognitive reappraisal.

    “CBT may therefore target fronto-limbic dysfunction directly via ERP or indirectly via cognitive reappraisal.”
    Quote in the paperSubstantial claim

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    Premisecitation

    CBT/ERP reduces intolerance of uncertainty in OCD, and reductions in intolerance of uncertainty occur before or alongside reductions in OCD symptoms.

    “Although not explicitly addressed in treatment, CBT/ERP has been shown to reduce IU in OCD and reductions in IU occurred prior to, or concurrent with, reductions in OCD symptoms [54–55].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [54] Belloch A, Cabedo E, Carrió C, Fernández-Alvarez H, García F, Larsson C. Group versus individual cognitive treatment for obsessive-compulsive disorder: changes in non-OCD symptoms and cognitions at post-treatment and one-year follow-up. Psychiatry Res. 2011;187:174–9. source

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    • cites [55] Overton SM, Menzies RG. Cognitive change during treatment of compulsive checking. Behav Change. 2005;22:172–84. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The sensorimotor circuit includes cortical and subcortical regions involved in generating and controlling motor behaviors and integrating sensory information.

    “The sensorimotor circuit includes cortical and subcortical regions involved in the generation and control of motor behaviors and integration of sensory information (Figure 3) [16, 72].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] van den Heuvel OA, van Wingend G, Soriano-Mase C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity. Eur Neuropsychopharmacol. 2016;26:810–27. source

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    • cites [72] Kurth F, Zilles K, Fox PT, Laird AR, Eickhoff SB. A link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis. Brain Struct Funct. 2010;214:519–34. source

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    Premisecitation

    SSRIs are the first-line pharmacological treatment for OCD.

    “there is evidence that selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for OCD [13]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43–51. source

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    Premisecitation

    fMRI neurofeedback targeting regulation of amygdala activity reduced amygdala activity and increased amygdala-vmPFC functional connectivity in non-psychiatric participants.

    “Although not tested in patients with OCD, fMRI-neurofeedback targeting regulation of amygdala activity was effective in reducing amygdala activity and increasing amygdala-vmPFC functional connectivity in non-psychiatric participants [66].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Paret C, Ruf M, Gerchen MF, Kluetsch R, Demirakca T, Jungkuntz M, et al. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal–limbic brain connectivity. Neuroimage. 2016;125:182–8. source

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    Premisecitation

    High-frequency rTMS of the left dlPFC reduced fear distress ratings and neural activity in the amygdala and other visual emotion processing areas and altered amygdala-dmPFC connectivity during a fear/OCD provocation task in OCD patients.

    “A sham-controlled study with OCD patients showed that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dlPFC reduced both fear distress ratings and neural activity in the amygdala and other visual emotion processing areas and altered functional connectivity between the amygdala and dmPFC during a fear/OCD provocation task [60].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [60] De Wit SJ, Van der Werf YD, Mataix-Cols D, Trujillo JP, Van Oppen P, Veltman DJ, et al. Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder. Psychological Med. 2015;45:3059–73. source

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    Premisecitation

    The bed nucleus of the stria terminalis is implicated in processing uncertain threat and is a potentially efficacious target for OCD symptom improvement.

    “Other work has indicated that the bed nucleus of the stria terminalis (BNST), a center of integration for limbic information that is implicated in processing uncertain threat [68], is a potentially efficacious target for OCD symptom improvements [69].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] LeDoux JE, Pine DS. Using neuroscience to help understand fear and anxiety: a two-system framework. Am J Psychiatry. 2016;173:1083–93. source

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    • cites [69] Luyten L, Hendrickx S, Raymaekers S, Gabriëls L, Nuttin B. Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder. Mol Psychiatry. 2016;21:1272–80. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CBT is an evidence-based psychotherapy for OCD that typically includes exposure and response prevention, with formats varying in cognitive reappraisal training.

    “For example, cognitive behavioral therapy (CBT) is an evidence-based form of psychotherapy for OCD that typically includes exposure and response prevention (ERP) with different formats varying in the degree of and procedures for training in cognitive reappraisal [50].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-Compulsive Disorder: Advances in Diagnosis and Treatment. JAMA. 2017;317:1358–67. source

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    Premisecitation

    DBS of the ventral anterior limb of the internal capsule in refractory OCD patients improved OCD symptoms and co-occurring depression and anxiety and changed functional connectivity between the amygdala and vmPFC.

    “one study examining DBS of the ventral anterior limb of the internal capsule (ALIC) in refractory OCD patients reported improvements in OCD symptoms and co-occurring depression and anxiety as well as changes in functional connectivity between the amygdala and vmPFC [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Fridgeirsson EA, Figee M, Luigjes J, van den Munckhof P, Schuurman PR, van Wingen G, et al. Deep brain stimulation modulates directional limbic connectivity in obsessive-compulsive disorder. Brain. 2020;143:1603–12. source

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    Interpretationreasoning

    Patients with fronto-limbic dysfunction associated with dysregulated fear may benefit most from CBT.

    “These findings lead to the hypothesis that patients who show fronto-limbic dysfunction associated with dysregulated fear may benefit most from CBT.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Habit-reversal training is an effective behavioral therapy for tic symptoms in Tourette syndrome, targets sensory phenomena, and reduces premonitory urges and tic severity in adults with Tourette syndrome.

    “Furthermore, habit-reversal training (Table 3), an effective behavioral therapy for tic symptoms used in TS, targets sensory phenomena and has been shown to reduce premonitory urges as well as tic symptom severity in adults with TS [98–99].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [98] Houghton DC, Capriotti MR, Scahill LD, Wilhelm S, Peterson AL, Walkup JT, et al. Investigating habituation to premonitory urges in behavior therapy for tic disorders. Behav Ther. 2017;48:834–46. source

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    • cites [99] McGuire JF, Piacentini J, Brennan EA, Lewin AB, Murphy TK, Small BJ, et al. A meta-analysis of behavior therapy for Tourette syndrome. J Psychiatr Res. 2014;50:106–12. source

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    Premisecitation

    The insula participates in emotional processing with the amygdala and other fronto-limbic structures and shows hyperactivity during emotional processing in OCD.

    “The insula, for example, participates in emotional processing with the amygdala and other fronto-limbic structures and, like those regions, also shows hyperactivity during emotional processing in OCD [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:563–71.

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  • May combine two claims.

    Premisecitation

    Several smaller pilot trials showed that repeated dosing of ondansetron over multiple weeks reduced overall symptom severity in OCD and Tourette syndrome, with potential utility as augmentation in SSRI-resistant OCD.

    “Interestingly, several smaller pilot trials showed that repeated dosing of ondansetron over multiple weeks reduced overall symptom severity in OCD [106–107] and TS [108], with potential utility as an augmentation strategy in SSRI-resistant OCD [106].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [106] Heidari M, Zarei M, Hosseini SM, Taghvaei R, Maleki H, Tabrizi M. Ondansetron or placebo in the augmentation of fluvoxamine response over 8 weeks in obsessive-compulsive disorder. Int Clin Psychopharmacol. 2014;29:344–50. source

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    • cites [107] Pallanti S, Bernardi S, Antonini S, Singh N, Hollander E. Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptake inhibitors: improvement with treatment and worsening following discontinuation. Eur Neuropsychopharmacol. 2014;24:375–80. source

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    • cites [108] Toren P, Weizman A, Ratner S, Cohen D, Laor N. Ondansetron treatment in Tourette’s disorder: a 3-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2005;66:499–503. source

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  • May combine two claims.

    Premisecitation

    Sensory phenomena are highly distressing, associated with increased obsessive-compulsive and tic severity and reduced quality of life, and are infrequently considered as outcomes in treatment trials.

    “Sensory phenomena, although highly distressing [95], associated with increased obsessive-compulsive and tic severity [73, 75, 95] and reduced quality of life [95], are infrequently considered as outcomes in treatment trials [96].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [95] Prado HS, Rosário MC, Lee J, Hounie AG, Shavitt RG, Miguel EC. Sensory phenomena in obsessive-compulsive disorder and tic disorders: a review of the literature. CNS Spectr. 2008;13:425–32. source

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    • cites [73] Ferrão YA, Shavitt RG, Prado H, Fontenelle LF, Malavazzi DM, de Mathis MA, et al. Sensory phenomena associated with repetitive behaviors in obsessive-compulsive disorder: an exploratory study of 1001 patients. Psychiatry Res. 2012;197:253–8. source

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    • cites [75] Rosario MC, Prado HS, Borcato S, Diniz JB, Shavitt RG, Hounie AG. Validation of the University of São Paulo Sensory Phenomena Scale: initial psychometric properties. CNS Spectr. 2009;14:315–23. source

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    • cites [96] Cavanna AE, Black KJ, Hallett M, Voon V. Neurobiology of the premonitory urge in Tourette’s syndrome: pathophysiology and treatment implications. J Neuropsychiatry Clin Neurosci. 2017;29:95–104. source

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    Premisecitation

    Sensorimotor volume increases were not correlated with sensory phenomena severity, but group differences remained after controlling for medication and comorbid conditions including Tourette syndrome.

    “Sensorimotor volume increases were not correlated with SP severity, but group differences remained after controlling for medication and comorbid conditions, including TS.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Subirà M, Sato JR, Alonso P, do Rosário MC, Segalàs C, Batistuzzo MC, et al. Brain structural correlates of sensory phenomena in patients with obsessive–compulsive disorder. J Psychiatry Neurosci. 2015;40:232–40. source

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  • May combine two claims.

    Premisereasoning

    Despite overlap in somatosensory and motor cortex, there are distinctions between the neurocircuitry of sensory phenomena and habit formation, with sensory phenomena additionally associated with the insula and habit formation involving subcortical as well as cortical sensorimotor areas.

    “Indeed, despite the overlap in somatosensory and motor cortex, there are some distinctions between the neurocircuitry, with sensory phenomena additionally associated with the insula and habit formation involving subcortical in addition to cortical sensorimotor areas.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    SSRIs decrease resting-state activity of the anterior insula in depression, suggesting that this treatment could modulate circuitry related to sensory phenomena.

    “The first-line pharmacological therapy for OCD (SSRIs) has been shown to decrease resting-state activity of the anterior insula in depression [103], suggesting that this form of treatment could be modulating circuitry related to SP.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] Chau DT, Fogelman P, Nordanskog P, Drevets WC, Hamilton JP. Distinct neural-functional effects of treatments with selective serotonin reuptake inhibitors, electroconvulsive therapy, and transcranial magnetic stimulation and their relations to regional brain function in major depression: a meta-analysis. Biol Psychiatry: Cogn Neurosci Neuroimaging. 2017;2:318–26.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some patients initially perform compulsions to elicit relief and continue performing them even after the rituals lose the ability to provide relief.

    “Similarly, content analyses have revealed that some patients initially perform compulsions to elicit a sense of relief and that even though their compulsive rituals lose the ability to provide relief over time, the patients continue to perform the behaviors [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Van Schalkwyk GI, Bhalla IP, Griepp M, Kelmendi B, Davidson L, Pittenger C. Toward understanding the heterogeneity in obsessive-compulsive disorder: Evidence from narratives in adult patients. Aust NZ J Psychiatry. 2016;50:74–81. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In its early stages, habit formation relies on dopaminergic reward signaling in the ventral affective circuit.

    “For instance, in its early stages, habit-formation relies on dopaminergic reward signaling in the ventral affective circuit [94].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Yin HH, Knowlton BJ. The role of the basal ganglia in habit formation. Nat Rev Neurosci. 2006;7:464–76. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Longer duration of illness predicted higher habit ratings, consistent with habit-like compulsions developing slowly over time.

    “Moreover, longer duration of illness predicted higher habit-ratings, in line with the idea that habit-like compulsions develop slowly over time [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Ferreira GM, Yücel M, Dawson A, Lorenzetti V, Fontenelle LF. Investigating the role of anticipatory reward and habit strength in obsessive-compulsive disorder. CNS Spectr. 2017;22:295–304. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neuroimaging studies report activation in the insula, parietal somatosensory regions, and motor/premotor regions during build-up and suppression of urges-for-action, with mid-posterior insula and cingulate motor area active during urges-for-action and the urge to tic.

    “Neuroimaging studies report activation in the insula, parietal somatosensory regions and motor/premotor regions to be involved in the build-up and suppression of urges-for-action [80–82], with a common region of mid-posterior insula and cingulate motor area (CMA) active during urges-for-action in non-psychiatric participants and the urge to tic in TS [81, see also 83–84].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [80] Berman BD, Horovitz SG, Morel B, Hallett M. Neural correlates of blink suppression and the buildup of a natural bodily urge. Neuroimage. 2012;59:1441–50. source

      Not checked in the free run.

    • cites [81] Jackson SR, Parkinson A, Kim SY, Schüermann M, Eickhoff SB. On the functional anatomy of the urge-for-action. Cogn Neurosci. 2011;2:227–43. source

      Not checked in the free run.

    • cites [82] Mazzone SB, Cole LJ, Ando A, Egan GF, Farrell MJ, et al. Investigation of the neural control of cough and cough suppression in humans using functional brain imaging. J Neurosci. 2011;31:2948–58. source

      Not checked in the free run.

    • cites [81, see also 83–84]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Theta oscillations rise with successful response inhibition and fall with inhibitory failures.

    “theta oscillations increase during successful response inhibition and decrease during inhibitory failures [131]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [131] Cavanagh JF, Frank MJ. Frontal theta as a mechanism for cognitive control. Trends Cogn Sci. 2014;18:414–21. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    H-coil TMS can modulate the insula and might therefore be useful for improving sensory phenomena in OCD.

    “Taken together, these findings suggest that H-coil TMS can modulate the insula and might therefore be useful in improving SP in OCD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    After neurofeedback, adolescents with ADHD had reduced symptoms, increased IFG activity, and stronger IFG-striatal connectivity during a non-trained inhibition task; these neural changes correlated with symptom improvement.

    “Post-training, adolescents with ADHD showed reduced symptom severity as well as increased IFG activity and stronger IFG-striatal functional connectivity during a (non-trained) response inhibition task and neural activity changes were correlated with symptom improvements [133–134].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [133] Alegria AA, Wulff M, Brinson H, Barker GJ, Norman LJ, Brandeis D, et al. Real‐time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder. Hum Brain Mapp. 2017;38:3190–209. source

      Not checked in the free run.

    • cites [134] Rubia K, Criaud M, Wulff M, Alegria A, Brinson H, Barker G, et al. Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in adolescents with ADHD. NeuroImage. 2019;188:43–58. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Open-label studies show that low-frequency rTMS to the supplementary motor area reduces OCD and tic symptom severity, although these studies did not examine effects on sensory phenomena specifically.

    “Open-label studies have shown efficacy in reducing OCD and tic symptom severity using low frequency (inhibitory) rTMS to the SMA [110–111 but see 112], though these studies did not examine effects on SP specifically.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [110–111 but see 112]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The ventral affective circuit comprises OFC, ventral striatum (especially NAcc), and thalamus, and supports reward-related processes.

    “The ventral affective circuit includes the OFC, the ventral striatum (particularly the nucleus accumbens, NAcc) and the thalamus (Figure 5) [16, 135] and is involved in reward-related processes.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] van den Heuvel OA, van Wingend G, Soriano-Mase C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity. Eur Neuropsychopharmacol. 2016;26:810–27. source

      Not checked in the free run.

    • cites [135] Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35:4–26. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Response inhibition is mediated in part by the inferior frontal gyrus and subthalamic nucleus, although other regions beyond the ventral cognitive circuit, such as the inferior parietal lobule and insula, are also involved.

    “Response inhibition is mediated in part by the inferior frontal gyrus (IFG) and the subthalamic nucleus (STN) (Table 2) [16, 119], although other regions beyond the ventral cognitive circuit, such as the inferior parietal lobule and insula, are also involved [120].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] van den Heuvel OA, van Wingend G, Soriano-Mase C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity. Eur Neuropsychopharmacol. 2016;26:810–27. source

      Not checked in the free run.

    • cites [119] Aron AR, Robbins TW, Poldrack RA. Inhibition and the right inferior frontal cortex: one decade on. Trends Cogn Sci. 2014;18:177–85. source

      Not checked in the free run.

    • cites [120] Swick D, Ashley V, Turken U. Are the neural correlates of stopping and not going identical? Quantitative meta-analysis of two response inhibition tasks. Neuroimage. 2011;56:1655–65. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The ACC participates in emotional processing, processes reward signals from the NAcc, and is hyperactive during reward tasks in OCD.

    “The anterior cingulate cortex (ACC), which participates in emotional processing functions of the fronto-limbic circuit [36], is also critically involved in processing reward signals relayed from the NAcc [135] and has been found to be hyperactive during reward tasks in OCD [155].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [36] Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:563–71.

      Not checked in the free run.

    • cites [135] Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35:4–26. source

      Not checked in the free run.

    • cites [155] Murray GK, Knolle F, Ersche KD, Craig KJ, Abbott S, Shabbir SS, et al. Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder. Psychopharmacology. 2019;236:2325–36. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In OCD, resting functional connectivity between NAcc and reward regions including OFC is increased and correlates with symptom severity.

    “increased functional connectivity between the NAcc and other reward circuit regions, including the OFC, during rest has been reported in OCD and this increased connectivity correlated with OCD symptom severity [140–141].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [140] Xie C, Ma L, Jiang N, Huang R, Li L, Gong L, et al. Imbalanced functional link between reward circuits and the cognitive control system in patients with obsessive-compulsive disorder. Brain Imaging Behav. 2017;11:1099–109. source

      Not checked in the free run.

    • cites [141] Jung WH, Kang D-H, Kim E, Shin KS, Jang JH, Kwon JS. Abnormal corticostriatal-limbic functional connectivity in obsessive–compulsive disorder during reward processing and resting-state. Neuroimage Clin. 2013;3:27–38. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Reduced reward sensitivity and/or heightened punishment anticipation are proposed to underlie reward responsiveness changes in OCD.

    “Reduced sensitivity to rewards and/or exaggerated anticipation of punishments have been proposed to underpin these reward responsiveness alterations [136–137] and can be observed in the clinical phenotype of OCD.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [136] Figee M, Vink M, de Geus F, Vulink N, Veltman DJ, Westenberg H, et al. Dysfunctional reward circuitry in obsessive-compulsive disorder. Biol Psychiatry. 2011;69:867–74. source

      Not checked in the free run.

    • cites [137] Kaufmann C, Beucke JC, Preuße F, Endrass T, Schlagenhauf F, Heinz A, et al. Medial prefrontal brain activation to anticipated reward and loss in obsessive–compulsive disorder. Neuroimage Clin. 2013;2:212–20. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OCD is associated with underactivation of NAcc and OFC during reward anticipation and reward-based decision-making, and with poorer reward-based decision-making and reward-learning performance.

    “Several studies have also reported underactivation of the NAcc and OFC during anticipation of reward (but not during anticipation of punishment) and during reward-based decision-making [136, 143–145] as well as poorer performance on reward-based decision-making and reward-learning tasks [146–147].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [136] Figee M, Vink M, de Geus F, Vulink N, Veltman DJ, Westenberg H, et al. Dysfunctional reward circuitry in obsessive-compulsive disorder. Biol Psychiatry. 2011;69:867–74. source

      Not checked in the free run.

    • cites [143] Admon R, Bleich-Cohen M, Weizmant R, Poyurovsky M, Faragian S, Hendler T. Functional and structural neural indices of risk aversion in obsessive–compulsive disorder (OCD). Psychiatry Res: Neuroimaging. 2012;203:207–13. source

      Not checked in the free run.

    • cites [144] Norman LJ, Carlisi CO, Christakou A, Murphy CM, Chantiluke K, Giampietro V, et al. Frontostriatal dysfunction during decision making in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Biol Psychiatry: Cogn Neurosci Neuroimaging. 2018;3:694–703.

      Not checked in the free run.

    • cites [145] Moreira PS, Macoveanu J, Marques P, Coelho A, Magalhaes R, Siebner HR, et al. Altered response to risky decisions and reward in patients with obsessive-compulsive disorder. J Psychiatry Neurosci. 2020;45:98–108. source

      Not checked in the free run.

    • cites [146] Grassi G, Pallanti S, Righi L, Figee M, Mantione M, Denys D, et al. Think twice: impulsivity and decision making in obsessive–compulsive disorder. J Behav Addict. 2015;4:263–72. source

      Not checked in the free run.

    • cites [147] Grassi G, Makris N, Pallanti S. Addicted to compulsion: assessing three core dimensions of addiction across obsessive-compulsive disorder and gambling disorder. CNS Spectr. 2019;20:392–401.

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    For some patients, dysregulated reward circuit activity interferes with other fronto-striatal circuits and contributes to OCD symptoms, and neuromodulation can reverse this.

    “the authors [159] suggested that, for some patients, dysregulated reward circuit activity interferes with the functioning of other (i.e. fronto-striatal) circuits, and contributes to OCD symptoms, and that this can be effectively reversed with neuromodulation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [159] Figee M, Luigjes J, Smolders R, Valencia-Alfonso CD, van Wingen G, de Kwaasteniet B, et al. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nat Neurosci. 2013;16:386–7. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NAcc DBS improves symptoms, reduces aberrant NAcc activity, and restores altered fronto-striatal connectivity in treatment-resistant OCD.

    “Neuromodulation of the NAcc with DBS has been shown to significantly improve symptoms, reduce aberrant NAcc activity and restore altered fronto-striatal connectivity in treatment-resistant OCD [159].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [159] Figee M, Luigjes J, Smolders R, Valencia-Alfonso CD, van Wingen G, de Kwaasteniet B, et al. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nat Neurosci. 2013;16:386–7. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dopamine-acting drugs such as methylphenidate normalize atypical reward-related performance and neural activity in ADHD.

    “Dopamine-acting drugs such as methylphenidate (Table 3) are effective in normalizing atypical reward-related performance and neural activity in ADHD [158]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [158] Rubia K, Halari R, Cubillo A, Mohammad AM, Brammer M, Taylor E. Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naive children with ADHD during a rewarded continuous performance task. Neuropharmacology. 2009;57:640–52. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Reward generalization is impaired in OCD, while punishment generalization is not.

    “Impaired generalization of reward but not punishment has also been found in OCD [148].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [148] Rouhani N, Wimmer GE, Schneier FR, Fyer AJ, Shohamy D, Simpson HB. Impaired generalization of reward but not loss in obsessive–compulsive disorder. Depression Anxiety. 2019;36:121–9. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Amygdala and vmPFC from the fronto-limbic circuit and STN from the ventral cognitive circuit contribute to ventral affective reward functions.

    “regions from other neurocircuits participate in the reward functions of the ventral affective circuit, including the amygdala and vmPFC from the fronto-limbic circuit [49] and the STN from the ventral cognitive circuit [128].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] Sescousse G, Caldú X, Segura B, Dreher JC. Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies. Neurosci Biobehav Rev. 2013;37:681–96. source

      Not checked in the free run.

    • cites [128] van Wijk BC, Alkemade A, Forstmann BU. Functional segregation and integration within the human subthalamic nucleus from a micro-and meso-level perspective. Cortex. 2020;131:103–13. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Executive dysfunctions may exacerbate obsessive-compulsive symptoms.

    “It is possible that these executive dysfunctions exacerbate obsessive-compulsive symptoms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Cognitive training programs for OCD targeting executive functions improved targeted executive functions and, in three studies, OCD symptoms.

    “The programs were found to improve the executive functions targeted [168–171] and, in three studies, OCD symptoms [169–171].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [168] Buhlmann U, Deckersbach T, Engelhard I, Cook LM, Rauch SL, Kathmann N, et al. Cognitive retraining for organizational impairment in obsessive-compulsive disorder. Psychiatry Res. 2006;144:109–16. source

      Not checked in the free run.

    • cites [169] Park HS, Shin YW, Ha TH, Shin MS, Kim YY, Lee YH, et al. Effect of cognitive training focusing on organizational strategies in patients with obsessive‐compulsive disorder. Psychiatry Clin Neurosci. 2006;60:718–26. source

      Not checked in the free run.

    • cites [170] Kashyap H, Reddy P, Mandadi S, Narayanaswamy JC, Sudhir PM, Reddy YJ. Cognitive training for neurocognitive and functional impairments in obsessive compulsive disorder: a case report. J Obsessive-Compuls Relat Disord. 2019;23:100480. source

      Not checked in the free run.

    • cites [171] Kalanthroff E, Steinman SA, Schmidt AB, Campeas R, Simpson HB. Piloting a personalized computerized inhibitory training program for individuals with obsessive-compulsive disorder. Psychother Psychosom. 2018;87:52–5. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Methylphenidate increases central dopamine and norepinephrine activity, improving executive/attentional functioning and emotion regulation.

    “Methylphenidate increases central dopamine and norepinephrine activity, which improves executive and attentional functioning and emotion regulation [173]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [173] Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255–70. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The clinical profiles of OCD proposed in the paper overlap, interact, and co-occur in individual patients.

    “the different clinical profiles of OCD we present here will overlap, interact, and co-occur in individual patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    fMRI neurofeedback can train non-psychiatric individuals to increase NAcc activity, which also elicits positive arousal.

    “fMRI-based neurofeedback has successfully been used in non-psychiatric samples to train individuals to increase NAcc activity, which also elicited feelings of positive arousal [161].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Greer SM, Trujillo AJ, Glover GH, Knutson B. Control of nucleus accumbens activity with neurofeedback. Neuroimage. 2014;96:237–44. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Working memory and planning appear impaired in OCD.

    “working memory and planning appear to be impaired in OCD [121, 164]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [121] Abramovitch A, Abramowitz JS, Mittelman A. The neuropsychology of adult obsessive–compulsive disorder: a meta-analysis. Clin Psychol Rev. 2013;33:1163–71. source

      Not checked in the free run.

    • cites [164] Snyder HR, Kaiser RH, Warren SL, Heller W. Obsessive-compulsive disorder is associated with broad impairments in executive function: a meta-analysis. Clin Psychological Sci. 2015;3:301–30. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Optimal dopamine levels for executive functions follow an inverted U-shaped curve and depend on baseline levels.

    “optimal dopamine levels for executive functions follow an inverted U-shaped curve and depend on the individual’s baseline levels [176].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [176] Cools R, D’Esposito M. Inverted-U–shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry. 2011;69:e113–25. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Case reports indicate methylphenidate can worsen OCD symptoms, and antipsychotics that reduce dopamine are effective for some patients.

    “there are some case reports that methylphenidate can worsen OCD symptoms [174] and for some patients antipsychotic medications that reduce dopamine levels are effective [175] (Table 3).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [174] Woolley JB, Heyman I. Dexamphetamine for obsessive-compulsive disorder. Am J Psychiatry. 2003;160:183. source

      Not checked in the free run.

    • cites [175] Bloch M, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11:622–32. source

      Not checked in the free run.

57 of 57

  • The paper relies on this without support.

    No published work has incorporated patients' subjective reports of their symptoms or considered specific treatment strategies directed at a range of clinical profiles and neurocircuit alterations.

    “To our knowledge, no published work has incorporated patients’ subjective reports of their experiences of symptoms or considered specific treatment strategies directed at a range of clinical profiles and neurocircuit alterations.”

  • The paper relies on this without support.

    There is no direct evidence linking sensory phenomena and habit formation to each other.

    “It is important to note that while sensory phenomena and habit formation are linked to similar circuitry, there is no direct evidence linking these features of OCD to each other (i.e. no studies have reported that the transition from goal-directed to habitual behavior is more common in patients with prominent sensory phenomena than those with fears or negative thoughts).”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • As part of the frontoparietal network, the parietal cortex interacts with core PFC regions to support attention and integration; hypoactivation due to PFC dysconnectivity may exacerbate cognitive inflexibility by impairing spatial attention and working memory updating, indirectly amplifying DMN rumination in OCD.

    “As part of the frontoparietal network (188), the parietal cortex interacts with core PFC regions to support attention and integration (189); hypoactivation due to PFC dysconnectivity (175) may exacerbate cognitive inflexibility by impairing spatial attention and working memory updating (190), indirectly amplifying DMN rumination in OCD (191).”

    From Neural mechanisms underlying cognitive inflexibility in obsessive-compulsive disorder: a review (2026) · cites this paper as [175]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Although the putamen and thalamus are integral to the CSTC, their limited task-specific abnormalities suggest downstream effects from core hubs like the CN and OFC.

    “Although the putamen and thalamus are integral to CSTC, their limited task-specific abnormalities suggest downstream effects from core hubs like CN and OFC (175, 184, 228).”

    From Neural mechanisms underlying cognitive inflexibility in obsessive-compulsive disorder: a review (2026) · cites this paper as [175]

    The Ventral affective circuit section identifies the thalamus and OFC as circuit components, and the Sensorimotor dysfunctions in OCD section reports a putamen and thalamus finding. Neither section says that putamen and thalamus have limited task-specific abnormalities or that their findings are downstream effects of the caudate nucleus and OFC. Our copy provides the circuit context, but not the proposed inference. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Abundant evidence implicates a role for urges and inhibitory control deficits in OCD.

    “Abundant evidence implicates a role for urges and inhibitory control deficits in OCD [6 -9].”

    From Habit as a therapeutic component in psychological treatment for obsessive-compulsive disorder: A randomised controlled feasibility study. (2026) · cites this paper as [7]

  • Novel behavioural interventions such as habit augmented ERP extend beyond traditional cognitive approaches and offer promise for moving toward a personalised treatment approach, based on measurable behavioural characteristics.

    “Novel behavioural interventions such as habit augmented ERP extend beyond traditional cognitive approaches and offer promise for moving toward a personalised treatment approach, based on measurable behavioural characteristics [6,7,83,84]”

    From Habit as a therapeutic component in psychological treatment for obsessive-compulsive disorder: A randomised controlled feasibility study. (2026) · cites this paper as [7]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • A cited sham-controlled trial is described as open-label

    Minor

    The text groups reference 110 among open-label studies, while that reference's title identifies it as a randomized sham-controlled trial.

1 of 1

Cites

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Research works printed but not linked: 1

  1. D’Urso G, Brunoni AR, Mazzaferro MP, Anastasia A, de Bartolomeis A, Mantovani A. Transcranial direct current stimulation for obsessive–compulsive disorder: a randomized, controlled, partial crossover trial. Depression Anxiety. 2016;33:1132–40. · DOI · Paper page

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Authors
Shephard, E., Stern, E. R., van den Heuvel, O. A., Costa, D. L. C., Batistuzzo, M. C., Godoy, P. B. G., Lopes, A. C., Brunoni, A. R., Hoexter, M. Q., Shavitt, R. G., Reddy, Y. C. J., Lochner, C., Stein, D. J., Simpson, H. B., & Miguel, E. C.
Affiliations
  • Universidade de São Paulo (BR)
  • Nathan Kline Institute for Psychiatric Research (US)
  • National Institute of Mental Health and Neurosciences (IN)
  • University of Cape Town (ZA)
  • Columbia University Irving Medical Center (US)
Corresponding author
Shephard, Elizabeth
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2021-01-07
Volume
26
Issue
9
Pages
4583-4604
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-020-01007-8
PMC
PMC8260628
OpenAlex
W3118678388
Semantic Scholar
a1974990289de823e8741be0486e8faeb4b5a6a9
Cited by
250
References
197
Citations by year
2026: 59 · 2025: 44 · 2024: 64 · 2023: 31 · 2022: 34 · 2021: 18
FWCI
4.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, cc-by)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (18/22396-7)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (2014‐2, 465550/2014-2)
  • National Institute of Mental Health (R01MH113250)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
Keywords
obsessive-compulsive disorder, clinical phenotype, neuropsychological findings, neuroimaging findings, neuromodulation, pharmacotherapy, behavior therapy
MeSH terms
Humans, Obsessive-Compulsive Disorder, Neuroimaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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