Precision psychiatry: a neural circuit taxonomy for depression and anxiety
Open accessAbstract
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.
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The neural, cognitive, information processing, and psychological patterns discussed above have broad transdiagnostic relevance, particularly with respect to other disorders of negative affect (e.g., anxiety, trauma-related conditions).
“Likewise, the neural, cognitive, information processing, and psychological patterns discussed above have broad transdiagnostic relevance, particularly with respect to other disorders of negative affect (e.g., anxiety, trauma-related conditions) 140 -that likewise respond to pharmacologic interventions with plasticity-enhancing properties 141,142 .”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [140]
The sections on the neural-circuit approach and negative-affect biotypes describe circuit dysfunction, attention, and emotional-processing patterns that cross depression and several anxiety diagnoses. They do not establish the same broad relevance for trauma-related conditions; PTSD appears in a cited study’s title, not in the paper’s account of its proposed biotypes. The available passages have no page numbers. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA focus on establishing correlations across levels of analysis, both before and after administering plasticity-enhancing interventions, will help clarify the degree to which an integrative neuroplasticity model may be relevant to some individual forms of depression and negative affect, but not others.
“Rather than assuming a unitary etiology, and a correspondingly uniform pathway to recovery from depression, a focus on establishing correlations across levels of analysis-both before and after administering plasticity-enhancing interventions-will help to clarify the degree to which an integrative neuroplasticity model may be relevant to some individual forms of depression and negative affect, but”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [140]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredBipolar disorder involves difficulty maintaining a consistent hierarchical inference: neurotransmitter and modulatory systems that set precision (like NMDA, dopamine and serotonin) fluctuate abnormally, causing the brain to over-fit at times and under-fit at others.
“One proposal is that bipolar disorder involves difficulty maintaining a consistent hierarchical inference: the neurotransmitter and modulatory systems that set precision (like NMDA, dopamine and serotonin) fluctuate abnormally, causing the brain to over-fit at times and under-fit at others (67).”
From Predictive coding and neurocomputational psychiatry: a mechanistic framework for understanding mental disorders (2026) · cites this paper as [67]
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Experimental — accuracy not yet measuredClusters 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]).”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [7]
OCD's complex phenomenology likely reflects widespread abnormalities across multiple brain regions and circuits.
“the complex phenomenology of the condition likely reflects widespread abnormalities across multiple brain regions and circuits encompassing a variety of emotional, cognitive, and behavioral domains, like most psychiatric disorders [5, 7].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [7]
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“However, average differences between groups may mask important heterogeneitybetween individuals (13),withsomepatientsnot showing these changes, or even demonstrating opposite patterns (e.”
Paying attention to attention in depression
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Self-citationToward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder
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How inflammation affects the brain in depression: a review of functional and structural MRI studies
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Deep Brain Stimulation for Depression Informed by Intracranial Recordings
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“Stereo-EEG recording contacts (white) sample regions within depression-relevant frontotemporal networks, including dlPFC and dmPFC (blue), dACC (green), vmPFC (yellow), OFC (pink), and MTL (red).”
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“Increased connectivity between nodes of the DMN and nodes of the FPCN would be expected to be associated with decreased depression and anxiety severity and improvements in attentional and metacognitive regulation (Mulders et al., 2015; Williams, 2016).”
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Deep phenotyping of attention impairments and the ‘Inattention Biotype’ in Major Depressive Disorder
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Self-citationTranslational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry
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- Authors
- Williams, L. M.
- Affiliations
- Stanford University (US)
- Corresponding author
- Williams, Leanne M
- ORCID
- Williams, Leanne M
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 3
- Issue
- 5
- Pages
- 472-480
- ISSN
- 2215-0366 (ISSN-L)
- PMC
- PMC4922884
- OpenAlex
- W2341692630
- Cited by
- 641
- References
- 74
- Citations by year
- 2026: 77 · 2025: 73 · 2024: 90 · 2023: 79 · 2022: 70 · 2021: 74 · 2020: 69 · 2019: 53 · 2018: 24 · 2017: 24 · 2016: 7
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health ((R01MH101496))
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- precision psychiatry, neural circuit dysfunction, depression, anxiety, mood disorders, anxiety disorders, functional neuroimaging, depression heterogeneity, individual differences
- MeSH terms
- Anxiety, Brain, Depression, Humans, Neural Pathways, Psychiatry
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