Pauls2014 - Obsessive-compulsive disorder, an integrative genetic and neurobiological perspective

  • Type:#article
  • Year read:#read2022
  • Subject: OCD Genetics
  • Bibtex: @pauls2014
  • Bibliography: Pauls, D. L., Abramovitch, A., Rauch, S. L., & Geller, D. A. (2014). Obsessive–compulsive disorder: An integrative genetic and neurobiological perspective. Nat. Rev. Neurosci., 15(6), 410–424.

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Key takeaways

  • In OCD, there is an imbalance between the direct- and indirect pathways of the cortico-striato-thalamo-cortical (CSTC) circuitry. There is excessive activity in the direct (Striatum -> globus pallidus interna and substantia nigra) pathway, and lower activity in the indirect pathway (striatum inhibits globus pallidus externa, which leads to more activity in the subthalamic nucleus, which inhibits the thalamus).
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The typical conceptualization of frontostriatal circuitry entails a direct and indirect pathway (FIG. 2). In healthy individuals, the excitatory, direct pathway is modulated by the indirect pathway’s inhibitory function (FIG. 2). Based on convergent findings from animal and human research, the prevailing model postulates that a lower threshold for activation of this system results in excessive activity in the direct pathway over the indirect pathway113, leading to hyperactivation of the orbitofrontal–subcortical pathway. As a result, exaggerated concerns about danger, hygiene or harm — mediated by the orbitofrontal cortex (OFC) — may result in persistent conscious attention to the perceived threat (that is, obsessions) and, subsequently, to compulsions aimed at neutralizing the perceived threat. The temporary relief that results from performing compulsions leads to reinforcement and repetitive (or ritualistic) behaviour when obsessions recur113 (FIG. 1).