The GABAergic Deficit Hypothesis of Major Depressive Disorder

By B. Luscher, Qiuying Shen, N. Sahir. Molecular Psychiatry, 2010

855 citations recorded by the source corpus.

Increasing evidence points to an association between major depressive disorders (MDDs) and diverse types of GABAergic deficits. In this review, we summarize clinical and preclinical evidence supporting a central and causal role of GABAergic deficits in the etiology of depressive disorders. Studies of depressed patients indicate that MDDs are accompanied by reduced brain concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and by alterations in the subunit composition of the principal receptors (GABAA receptors) mediating GABAergic inhibition. In addition, there is abundant evidence that suggests that GABA has a prominent role in the brain control of stress, the most important vulnerability factor in mood disorders. Furthermore, preclinical evidence suggests that currently used antidepressant drugs (ADs) designed to alter monoaminergic transmission and nonpharmacological therapies may ultimately act to counteract GABAergic deficits. In particular, GABAergic transmission has an important role in the control of hippocampal neurogenesis and neural maturation, which are now established as cellular substrates of most if not all antidepressant therapies. Finally, comparatively modest deficits in GABAergic transmission in GABAA receptor-deficient mice are sufficient to cause behavioral, cognitive, neuroanatomical and neuroendocrine phenotypes, as well as AD response characteristics expected of an animal model of MDD. The GABAergic hypothesis of MDD suggests that alterations in GABAergic transmission represent fundamentally important aspects of the etiological sequelae of MDDs that are reversed by monoaminergic AD action.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Cellular and Molecular Neuroscience

View Paper: https://www.semanticscholar.org/paper/460a94ca121bdd2bbb76edd24d90f79f216c8cab

How researchers see this paper

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

In Behavioral Neuroscience

1. G. Sanacora
2. R. Duman
3. John H. Krystal

In Biological Psychiatry

1. R. Duman
2. G. Sanacora
3. John H. Krystal
4. K. Al-Harbi

In Cellular and Molecular Neuroscience

1. G. Sanacora
2. R. Duman
3. John H. Krystal
4. E. Nestler
5. Bruce S. McEwen
6. L. Monteggia
7. H. Schmidt
8. J. Warner-Schmidt

Citations in the corpus

• Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience (2015, background): “In this context, given findings that GABA deficits are prevalent in MDD (63) and that GABA concentrations in pericingulate cortex may control fluctuations of activity in the DMN (64), future work might explore more explicitly the relation between the DMN and the pericingulate GABA-ergic system in…”
• A review of depression and suicide risk assessment using speech analysis (2015, background): “, 2008; Sharp and Cowen, 2011), neurotransmitter dysfunction (Luscher et al., 2011; Poulter et al., 2008) and genetic abnormalities (Dwivedi et al.”
• Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments (2019, background): “There is also evidence that administration of adrenal glucocorticoids can lead to deficits of GABA neurotransmission (Ghosal et al., 2017; Luscher et al., 2011; Northoff and Sibille, 2014).”