Neurobiology of obsessive-compulsive disorder: insights into neural circuitry dysfunction through mouse genetics
Open accessAbstract
The precise causal factors for obsessive-compulsive disorder (OCD) are not known, although, decades of research have honed in on the cortico-striatal-thalamo-cortical (CSTC) circuitry in the brain as a critical pathway involved in obsessions and the intimately linked compulsive-repetitive behaviors. Recent progress in human and mouse genetics have led to the identification of novel candidate susceptibility genes, which in turn have facilitated a more focused approach to unraveling the nature of circuitry dysfunction in OCD. The ability to perform invasive techniques in genetic animal models of OCD will be crucial for rapid advances in this field, and as such we review the most recent developments and highlight the importance of searching out common circuitry defects underlying compulsive-repetitive behaviors.
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An imbalance between the direct and indirect pathways, specifically overactivity in the direct pathway, is thought to contribute to OCD pathology by creating a positive feedback loop resulting in CSTC circuit hyperactivity.
“An imbalance between these two pathways is thought to contribute to OCD pathology, that is, overactivity in the direct pathway (critical for initiation and suppression of behavior) creating a positive feedback loop resulting in CSTC circuit hyperactivity (Saxena et al., 2001; see also Maia et al., 2008; Ting & Feng, 2011) (Vahabzadeh & McDougle, 2014; van den Heuvel et al., 2016).”
From Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction (2023) · cites this paper as Ting & Feng, 2011
The 'Theoretical framework for circuitry dysfunction in OCD' section (page not supplied) describes a hypothesis in which excessive direct-pathway activation disrupts the balance between basal ganglia pathways and causes orbitofrontal-subcortical loop hyperactivity associated with OCD symptoms. It does not describe a positive feedback loop or specify the direct pathway's role in both initiating and suppressing behavior. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChanging the balance of activity between direct and indirect pathways can promote or inhibit the selection of appropriate behavior sequences.
“A popular model suggests that changing the balance of activity between direct and indirect pathways can either promote or inhibit the selection of appropriate behavior sequences 42,50.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [50]
Obsessions and compulsions result from malfunctioning neural circuits that include OFC, ACC, caudate, and anterior thalamus.
“they consistently share the idea that obsessions and compulsions somehow result from malfunctioning neural circuits that include OFC, ACC, caudate, and anterior thalamus (Fig.2).”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [50]
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References 45 · Cited by 143
- Authors
- Ting, J. T., & Feng, G.
- Affiliations
- McGovern Institute for Brain Research (US)
- Broad Institute (US)
- Corresponding author
- Feng, Guoping
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 21
- Issue
- 6
- Pages
- 842-848
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC3192923
- OpenAlex
- W1997650932
- Cited by
- 143
- References
- 45
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 11 · 2023: 11 · 2022: 11 · 2021: 19 · 2020: 12 · 2019: 10 · 2018: 5 · 2017: 9 · 2016: 7 · 2015: 13 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Hartwell Foundation (R01MH081201)
- National Alliance for Research on Schizophrenia and Depression
- Broad Institute (R01MH081201)
- Simons Foundation Autism Research Initiative (R01MH081201)
- Scheme for Promotion of Academic and Research Collaboration
- National Institutes of Health
- Stanley Center for Psychiatric Research, Broad Institute
- National Institute of Mental Health (F32MH084460, R01MH081201)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- obsessive-compulsive disorder, obsession, susceptibility genes, genetic mouse models, neural circuit dysfunction
- MeSH terms
- Animals, Disease Models, Animal, Humans, Obsessive-Compulsive Disorder, Mice
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