Precision psychiatry: a neural circuit taxonomy for depression and anxiety

Abstract

Although there have been tremendous advances in the understanding of human dysfunctions in the brain circuitry for self-reflection, emotion, and cognitive control, a brain-based taxonomy for mental disease is still lacking. As a result, these advances have not been translated into actionable clinical tools, and the language of brain circuits has not been incorporated into training programmes. To address this gap, I present this synthesis of published work, with a focus on functional imaging of circuit dysfunctions across the spectrum of mood and anxiety disorders. This synthesis provides the foundation for a taxonomy of putative types of dysfunction, which cuts across traditional diagnostic boundaries for depression and anxiety and includes instead distinct types of neural circuit dysfunction that together reflect the heterogeneity of depression and anxiety. This taxonomy is suited to specifying symptoms in terms of underlying neural dysfunction at the individual level and is intended as the foundation for building mechanistic research and ultimately guiding clinical practice.

Figure 1. Large-scale intrinsic and task-evoked circuits identified in published work

aMPFC=anterior medial prefrontal cortex. AG=angular gyrus. PCC=posterior cingulate cortex (includes precuneus). dACC=dorsal anterior cingulate cortex. aI=anterior insula. TP=temporal pole. SLEA=sublenticular extended amygdala. ACC/MPFC=dorsal medial prefrontal cortex (includes dorsal ACC and vMPFC, including ventral—subgenual and pregenual—and rostral ACC). msPFC=medial superior prefrontal cortex. LPFC=lateral prefrontal cortex. aIPL=anterior inferior parietal lobule. MPFC=medial prefrontal cortex. vMPFC=ventromedial prefrontal cortex. OFC=orbitofrontal cortex. ACC=anterior cingulate cortex. DLPFC=dorsolateral prefrontal cortex (includes anterior prefrontal cortex and inferior frontal cortex). PCG=precentral gyrus. DPC=dorsal parietal cortex.

Figure 2. Proposed taxonomy of putative biotypes of neural circuit dysfunction for depression and anxiety based on published work

The proposed phenotype associated with each proposed neural dysfunction is mentioned above each type of dysfunction. aMPFC=anterior medial prefrontal cortex. AG=angular gyrus. PCC=posterior cingulate cortex (includes precuneus). dACC=dorsal anterior cingulate cortex. aI=anterior insula. TP=temporal pole. SLEA=sublenticular extended amygdala. ACC/MPFC=dorsal medial prefrontal cortex (includes dorsal ACC and vMPFC, including ventral—subgenual and pregenual— and rostral ACC). msPFC=medial superior prefrontal cortex. LPFC=lateral prefrontal cortex. aIPL=anterior inferior parietal lobule. MPFC=medial prefrontal cortex. vMPFC=ventromedial prefrontal cortex. OFC=orbitofrontal cortex. ACC=anterior cingulate cortex. DLPF=dorsoateral prefrontal cortex (includes anterior prefrontal cortex and inferior frontal cortex). PCG=precentral gyrus. DPC=dorsal parietal cortex.

Figure 3. Speculative connection between neural circuit biotypes for depression and anxiety and potentially suitable interventions

aMPFC=anterior medial prefrontal cortex. AG=angular gyrus. PCC=posterior cingulate cortex (includes precuneus). dACC=dorsal anterior cingulate cortex. aI=anterior insula. TP=temporal pole. SLEA=sublenticular extended amygdala. ACC/mPFC=dorsal medial prefrontal cortex (includes dorsal ACC and vMPFC, including ventral—subgenual and pregenual—and rostral ACC). msPFC=medial superior prefrontal cortex. LPFC=lateral prefrontal cortex. aIPL=anterior inferior parietal lobule. mPFC=medial prefrontal cortex. vMPFC=ventromedial prefrontal cortex. OFC=orbitofrontal cortex. ACC=anterior cingulate cortex. DLPF=dorsolateral prefrontal cortex (includes anterior prefrontal cortex and inferior frontal cortex). PCG=precentral gyrus. DPC=dorsal parietal cortex. TMS=transcranial magnetic stimulation. DBS=deep-brain stimulation.