The Subgenual Anterior Cingulate Cortex in Mood Disorders

By Wayne C. Drevets, Jonathan Savitz, M. Trimble. CNS Spectrums, 2008

1,090 citations recorded by the source corpus.

ABSTRACT 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.

Subfields: Cognitive Neuroscience, Neurology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/ae6030e638cb2edf474229388bb8651e46fb9936

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

In Neurology

In Psychiatry and Mental health

Citations in the corpus

Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008, background): “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).”
Neurocircuitry of Mood Disorders (2010, background): “…matter volume in the prefrontal cortex of lithium-responsive BD subjects to an extent that would reduce or eliminate partial volume effects (Moore et al, 2008; Drevets et al, 2008) the sgACC metabolism appears abnormally elevated relative to healthy controls (Mah et al, 2007; Bauer et al, 2005).”
Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields (2013, neutral): “Significant differences in connectivity were seen with the subgenual cingulate (SG), a region repeatedly implicated in antidepressant response and an effective DBS target (Drevets et al., 2008;Mayberg, 2009;Mayberg et al., 2005).”
Social functioning in major depressive disorder. (2016, neutral): “Consistent with the increased activity, 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).”
The influence of negative emotions on pain: Behavioral effects and neural mechanisms (2009, neutral): “In accordance with these suggested functions, malfunctioning of the ACC has been reported for post-traumatic stress disorder (Liberzon and Martis, 2006), major depressive disorder and bipolar disorder (Drevets et al., 2008) as well as anxiety disorders (Etkin and Wager, 2007).”
Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. (2012, background): “The subgenual has been observed to be hyperactive in depression and a decrease in this hyperactivity is associated with antidepressant response (16,17,58) (Table 1).”
Self-awareness, self-regulation, and self-transcendence (S-ART): a framework for understanding the neurobiological mechanisms of mindfulness (2012, methodology): “Through an interaction with the sgACC, there is evidence suggesting a mechanism for appraising the value of stimuli with respect to current goals and decisions, while some data suggest a role in modulating emotion and disengagement through executive control mechanisms (Drevets et al., 2008; Roy et a”
The Role of Sleep in Emotional Brain Function (2014, background): “…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).”
Phasic and sustained fear in humans elicits distinct patterns of brain activity (2010, neutral): “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).”
Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity (2012, neutral): “Significant differences in connectivity were seen in a variety of cortical and limbic regions including the subgenual cingulate , a region repeatedly implicated in antidepressant response to a variety of treatment modalities (Drevets et al., 2008; Mayberg, 2009; Mayberg et al., 2005).”