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Review
. 2021 Sep;26(9):4583-4604.
doi: 10.1038/s41380-020-01007-8. Epub 2021 Jan 7.

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

Elizabeth Shephard  1   2 , Emily R Stern  3   4 , Odile A van den Heuvel  5   6 , Daniel L C Costa  7 , Marcelo C Batistuzzo  7 , Priscilla B G Godoy  7 , Antonio C Lopes  7 , Andre R Brunoni  7 , Marcelo Q Hoexter  7 , Roseli G Shavitt  7 , Y C Janardhan Reddy  8 , Christine Lochner  9 , Dan J Stein  10 , H Blair Simpson  11 , Euripedes C Miguel  12
Affiliations
Review

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

Elizabeth Shephard et al. Mol Psychiatry. 2021 Sep.

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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Conflict of interest statement

Conflicts of Interests

The authors Elizabeth Shephard, Emily R. Stern, Odile A. van den Heuvel, Daniel L.C. Costa, Priscilla B.G. Godoy, Marcelo C. Batistuzzo, Antonio C. Lopes, Marcelo Q. Hoexter, Christine Lochner, and Euripedes C. Miguel have no conflicts of interests to declare. Roseli G. Shavitt has received consulting honoraria from Lundbeck and a travel grant from LIBBS. Andre R Brunoni has received funding from the São Paulo Research Foundation (2017/50223–6, 2018/10861–7), the Brazilian National Council of Scientific Development productivity support (PQ-1B) and the University of São Paulo Medical School productivity support (PIPA-A), and is the Chief Medical Advisor of Flow Neuroscience (Malmö, Sweden) and has a small equity in this company. Janardhan Reddy Y.C. has received support from the various Government of India funding agencies for research on OCD, including the Department of Biotechnology (DBT), Department of Science and Technology (DST), and the Indian Council of Medical Research (ICMR); he is also currently involved in an NIMH multicenter international study on OCD. Dan J. Stein has received research grants and/or consultancy honoraria from Lundbeck and Servier. H. Blair Simpson has received research funds for a multi-site industry sponsored clinical trial from Biohaven Inc., royalties from Cambridge University Press and UpToDate Inc., and a stipend from the American Medical Association for serving as an Associate Editor for JAMA Psychiatry.

Figures

Figure 1.
Figure 1.. Five circuits involved in OCD
according to van den Heuvel et al. (2016) [16]. The fronto-limbic circuit (red) includes the amygdala and ventromedial prefrontal cortex (vmPFC) and is involved in producing emotional responses, such as fear and anxiety. The sensorimotor circuit (green) includes the supplementary motor area (SMA), putamen and thalamus and is involved in producing and controlling motor behavior and the integration of sensory information. The ventral cognitive circuit (yellow) includes the inferior frontal gyrus (IFG), ventrolateral prefrontal cortex (vlPFC), ventral caudate and thalamus and is involved in self-regulatory behavioral control. The ventral affective circuit (purple) includes the orbitofrontal cortex, nucleus accumbens (NAcc) and thalamus and is involved in processing and responding to reward. The dorsal cognitive circuit (blue) includes the dorsolateral prefrontal cortex (dlPFC), dorsomedial prefrontal cortex (dmPFC), dorsal caudate and thalamus and is involved in executive functions (e.g. working memory, planning) and emotion regulation.
Figure 2
Figure 2. The fronto-limbic circuit
includes the amygdala and ventromedial prefrontal cortex (vmPFC, consisting of ventral orbitofrontal cortex, ventral anterior cingulate cortex and the ventral part of medial frontal gyrus). These regions are structurally and functionally connected with each other to form a network that generates emotional responses (amygdala and NAcc) and evaluates whether those responses are appropriate or require regulation (vmPFC). The fronto-limbic circuit is connected with the hippocampus and regions from other circuits that are involved in top-down behavioral control, including the dorsolateral prefrontal cortex (dlPFC) from the dorsal cognitive circuit, and can recruit these regions to dampen fronto-limbic activity thereby facilitating emotional regulation.
Figure 3.
Figure 3.. The sensorimotor circuit
includes cortical and subcortical regions involved in the generation and control of motor behaviours (primary motor cortex - precentral gyrus, supplementary motor area, putamen, globus pallidus and thalamus) and the integration of sensory information (postcentral gyri, secondary somatosensory cortex, insula).
Figure 4.
Figure 4.. The ventral cognitive circuit
includes prefrontal (inferior frontal gyrus, ventrolateral prefrontal cortex) and subcortical regions (ventral caudate and thalamus) involved in self-regulatory functions. The inferior frontal gyrus (IFG), particularly in the right hemisphere, and ventral caudate together act as a “braking system”, which implements response inhibition, the ability to withhold inappropriate responses.
Figure 5.
Figure 5.. The ventral affective circuit
includes the orbitofrontal cortex (OFC), ventral striatum (particularly the nucleus accumbens, NAcc) and the thalamus. This circuit is crucially involved in reward functions which are largely mediated by dopaminergic signaling.
Figure 6.
Figure 6.. The dorsal cognitive circuit
involves the pre-supplementary motor area (pre-SMA), dorsolateral PFC (dlPFC), dorsomedial PFC (dmPFC), dorsal caudate and thalamus and handles executive functions such as working memory and planning/organization and emotion regulation.
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References

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