Why are cortical GABA neurons relevant to internal focus in depression? A cross-level model linking cellular, biochemical and neural network findings.
Georg Northoff, Etienne Sibille
Molecular Psychiatry September 2014 DOI: 10.1038/mp.2014.68 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Depression |
| Key points | Argues that deficits in GABA-mediated inhibitory regulation in key brain regions may underlie a shift in resting-state activity between the perigenual anterior cingulate cortex and dorsolateral prefrontal cortex, producing a network imbalance between default-mode and executive networks that manifests as increased self-focus and rumination in depression. Proposes that this model offers new hypotheses about how internal and external mental contents are balanced in healthy subjects. |
Abstract
Major depression is a complex and severe psychiatric disorder whose symptomatology encompasses a critical shift in awareness, especially in the balance from external to internal mental focus. This is reflected by unspecific somatic symptoms and the predominance of the own cognitions manifested in increased self-focus and rumination. We posit here that sufficient empirical data has accumulated to build a coherent biologic model that links these psychologic concepts and symptom dimensions to observed biochemical, cellular, regional and neural network deficits. Specifically, deficits in inhibitory γ-aminobutyric acid regulating excitatory cell input/output and local cell circuit processing of information in key brain regions may underlie the shift that is observed in depressed subjects in resting-state activities between the perigenual anterior cingulate cortex and the dorsolateral prefrontal cortex. This regional dysbalance translates at the network level in a dysbalance between default-mode and executive networks, which psychopathologically surfaces as a shift in focus from external to internal mental content and associated symptoms. We focus here on primary evidence at each of those levels and on putative mechanistic links between those levels. Apart from its implications for neuropsychiatric disorders, our model provides for the first time a set of hypotheses for cross-level mechanisms of how internal and external mental contents may be constituted and balanced in healthy subjects, and thus also contributes to the neuroscientific debate on the neural correlates of consciousness.
Comparable studies
Other theoretical and historical papers on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Mindfulness-based cognitive therapy for depression | 2006 | Theoretical or philosophical paper | |
| Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame | 2020 | Theoretical or philosophical paper | |
| The Yale Manual for Psilocybin-Assisted Therapy of Depression (using Acceptance and Commitment Therapy as a Therapeutic Frame) | 2020 | Theoretical or philosophical paper | |
| Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments | 2022 | Theoretical or philosophical paper | |
| Improving cognitive functioning in major depressive disorder with psychedelics: A dimensional approach | 2021 | Theoretical or philosophical paper |
Citations in the library
Cited by 5
- Is the self a higher-order or fundamental function of the brain? The "basis model of self-specificity" and its encoding by the brain's spontaneous activity. Cognitive Neuroscience 2016
- Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine Current Neuropharmacology March 10, 2016
- Too Fast or Too Slow? Time and Neuronal Variability in Bipolar Disorder—A Combined Theoretical and Empirical Investigation Schizophrenia Bulletin March 14, 2017
- Preliminary analysis of ayahuasca-induced anatomical alterations in the somatosensory cortex of juvenile non-human primates (Callithrix jacchus) subjected to chronic stress Translational Psychiatry February 19, 2026
- Affective neuroscience of self-generated thought. Annals of the New York Academy of Sciences May 12, 2018
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- Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network Neuroimage September 18, 2012
and 4 more in the library