The subgenual anterior cingulate cortex in mood disorders
Open accessAbstract
The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this “subgenual” ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended “visceromotor network” of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.
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The differential effects of these drugs on dendritic atrophy in stressed rats resemble their effects on sgACC volume in humans with BD.
“The differential effects of these drugs on dendritic atrophy in stressed rats thus resemble their effects on sgACC volume in humans with BD (Moore et al. 2008; Drevets et al. 1997; Drevets and Savitz 2008).”
From Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008) · cites this paper as Drevets and Savitz 2008
The section on rodent models of repeated stress says lithium reversed dendritic atrophy in stressed rats and likens this to its effect on gray-matter reductions in bipolar disorder. The structural neuroimaging section reports greater sgACC volume in lithium-treated bipolar patients. Our copy does not establish the claimed differential effects of multiple drugs on both rat dendritic atrophy and human sgACC volume; page numbers are unavailable. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA meta-analysis on volumetric fMRI studies has revealed a volume reduction of the ACC compared with healthy control subjects.
“a meta-analysis on volumetric fMRI studies has revealed a volume reduction of ACC compared with healthy control subjects (Drevets et al., 2008;Zhao et al., 2014).”
From Social functioning in major depressive disorder (2016) · cites this paper as Drevets et al., 2008
In healthy men, intranasal oxytocin administration can increase empathic concern, enhance empathic accuracy and improve ToM.
“In healthy men, intranasal oxytocin administration can increase empathic concern (Hurlemann et al., 2010), enhance empathic accuracy (Bartz et al., 2010) and improve ToM (Domes et al., 2006).”
From Social functioning in major depressive disorder (2016) · cites this paper as Domes et al., 2006
Biomarkers that distinguish between depressed and non-depressed individuals have been identified at the neural level.
“Biomarkers that distinguish between depressed and non-depressed individuals have been identified at the neural level (Drevets et al, 2008; Northoff et al, 2011)”
From Resting-state cortico-thalamic-striatal connectivity predicts response to dorsomedial prefrontal rTMS in major depressive disorder (2014) · cites this paper as Drevets et al, 2008
Depression has been associated with functional and structural abnormalities in subgenual cingulate, thalamus, striatum, and limbic regions.
“Depression has been associated with functional and structural abnormalities in subgenual cingulate, thalamus, striatum, and limbic regions (Alcaro et al, 2010; Drevets et al, 2008; Heller et al, 2009, 2013; Mayberg, 2009; Phillips et al, 2003).”
From Resting-state cortico-thalamic-striatal connectivity predicts response to dorsomedial prefrontal rTMS in major depressive disorder (2014) · cites this paper as Drevets et al, 2008
Clinical studies indicate that metabolism in sACC is elevated in the depressed phase relative to the remitted phase of the same patients with major depressive disorder.
“Clinical studies indicate that metabolism in sACC is elevated in the depressed phase relative to the remitted phase of the same patients with major depressive disorder (Drevets et al., 2008).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Drevets et al., 2008
Anterior cingulate and neighbouring medial frontal regions and linked basal ganglia have been linked with mood regulation, including depression and anxiety.
“In addition, this structure and neighbouring medial frontal regions and linked basal ganglia have been also been strikingly linked with mood regulation, including depression and anxiety (Drevets et al., 2008; Gutman et al., 2009; Johansen-Berg et al., 2008; Mayberg et al., 2005).”
From The human parental brain: In vivo neuroimaging (2011) · cites this paper as Drevets et al., 2008
The subgenual ACC is especially involved in fear responses and shows abnormal activity in mood disorders.
“which is especially involved in fear responses and shows abnormal activity in mood disorders (Drevets et al, 2008).”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Drevets et al, 2008
The key regions that have gained consensus for involvement in MDD include the limbic cortex (amygdala, hippocampus), the cingulate cortex, dorsal striatum, and the frontal lobe (DLPFC and MPFC).
“The key regions that have gained consensus for an involvement in MDD include the limbic cortex (amygdala, hippocampus), the cingulate cortex, dorsal striatum and the frontal lobe (dorsolateral prefrontal cortex [DLPFC] and medial prefrontal cortex [MPFC]).”
From Widespread reductions in gray matter volume in depression (2013) · cites this paper as Drevets et al., 2008
A substantial body of imaging data demonstrates spatially distributed functional abnormalities occurring throughout the brain in MDD.
“A substantial body of imaging data demonstrates spatially distributed functional abnormalities occurring throughout the brain in MDD (Drevets et al., 2008).”
From Widespread reductions in gray matter volume in depression (2013) · cites this paper as Drevets et al., 2008
The functional role of the cingulate cortex-and specifically the ACC-in depression is well described.
“The functional role of the cingulate cortex—and specifically the ACC—in depression is well described (Drevets et al., 2008).”
From Widespread reductions in gray matter volume in depression (2013) · cites this paper as Drevets et al., 2008
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- [38]Drevets WC Bogers W Raichie ME Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism Eur Neuropsychopharmacol 2002 12 527 544 12468016
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- [93]Drevets WC Furey ML Squire L Emotional disorders: depression and the brain The New Encyclopedia of Neuroscience 4 New York, NY Elsevier Publishing, Inc In press
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“The differential effects of these drugs on dendritic atrophy in stressed rats thus resemble their effects on sgACC volume in humans with BD (Moore et al. 2008; Drevets et al. 1997; Drevets and Savitz 2008).”
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“…the mechanisms underlying affective brain processes (Critchley 2005, Delgado et al 2006, Hartley & Phelps 2010, Ochsner et al 2009), translationally bridging animal models of emotion regulation and relevant clinical disorders (Davidson 2002, Delgado et al 2006, Drevets et al 2008, Etkin 2010).”
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“As aberrant sgACC-DMN hyperconnectivity has been observed in depression (Connolly et al., 2013; Drevets et al., 2008), it has been speculated that decreased connectivity in these regions mediated by mindfulness training may relate to an antidepressant effect (Yang et al., 2016).”
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- Authors
- Drevets, W. C., Savitz, J., & Trimble, M.
- Affiliations
- National Institutes of Health (US)
- National Institute of Mental Health (US)
- National Hospital for Neurology and Neurosurgery (GB)
- Venue
- CNS Spectrums
- Publisher
- Cambridge University Press (CUP)
- Published
- 2008-08
- Volume
- 13
- Issue
- 8
- Pages
- 663-681
- ISSN
- 1092-8529 (ISSN-L)
- 2165-6509
- PMC
- PMC2729429
- OpenAlex
- W1582811168
- Cited by
- 1,109
- References
- 109
- Citations by year
- 2026: 55 · 2025: 58 · 2024: 64 · 2023: 48 · 2022: 68 · 2021: 112 · 2020: 62 · 2019: 63 · 2018: 57 · 2017: 55 · 2016: 72 · 2015: 63 · 2014: 68 · 2013: 70 · 2012: 68
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS Spectrums (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (Z01MH002790)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- subgenual anterior cingulate cortex, mood disorders, major depressive disorder, bipolar disorder, gray matter volume, antidepressant response, deep brain stimulation, stress response, emotional behavior, neuroendocrine regulation, autonomic responses
- MeSH terms
- Corpus Callosum, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Mood Disorders
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