scholarly journals Revisiting the Monoamine Hypothesis of Depression: A New Perspective

2014 ◽  
Vol 6 ◽  
pp. PMC.S11375 ◽  
Author(s):  
Joel S. Goldberg ◽  
Clifton E. Bell ◽  
David A. Pollard
Keyword(s):  
Good Evidence ◽  
Aminobutyric Acid ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Laboratory Findings ◽  
Refractory Depression ◽  
Potential Benefits ◽  
New Perspective ◽  
Long Chain ◽  
Hplc Data

As the incidence of depression increases, depression continues to inflict additional suffering to individuals and societies and better therapies are needed. Based on magnetic resonance spectroscopy and laboratory findings, gamma aminobutyric acid (GABA) may be intimately involved in the pathophysiology of depression. The isoelectric point of GABA (pI = 7.3) closely approximates the pH of cerebral spinal fluid (CSF). This may not be a trivial observation as it may explain preliminary spectrophotometric, enzymatic, and HPLC data that monoamine oxidase (MAO) deaminates GABA. Although MAO is known to deaminate substrates such as catecholamines, indoleamines, and long chain aliphatic amines all of which contain a lipophilic moiety, there is very good evidence to predict that a low concentration of a very lipophilic microspecies of GABA is present when GABA pI = pH as in the CSF. Inhibiting deamination of this microspecies of GABA could explain the well-established successful treatment of refractory depression with MAO inhibitors (MAOI) when other antidepressants that target exclusively levels of monoamines fail. If further experimental work can confirm these preliminary findings, physicians may consider revisiting the use of MAOI for the treatment of non-intractable depression because the potential benefits of increasing GABA as well as the monoamines may outweigh the risks associated with MAOI therapy.

scholarly journals Imaging the Pathophysiology of Essential Tremor—A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Florian Holtbernd ◽  
N. Jon Shah
Keyword(s):  
Magnetic Resonance ◽  
Essential Tremor ◽  
Neurodegenerative Disorder ◽  
Aminobutyric Acid ◽  
Emission Computed Tomography ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Imaging Studies ◽  
Limited Evidence ◽  
Neurotransmitter System

Background: The pathophysiology underlying essential tremor (ET) still is poorly understood. Recent research suggests a pivotal role of the cerebellum in tremor genesis, and an ongoing controversy remains as to whether ET constitutes a neurodegenerative disorder. In addition, mounting evidence indicates that alterations in the gamma-aminobutyric acid neurotransmitter system are involved in ET pathophysiology. Here, we systematically review structural, functional, and metabolic neuroimaging studies and discuss current concepts of ET pathophysiology from an imaging perspective.Methods: We conducted a PubMed and Scopus search from 1966 up to December 2020, entering essential tremor in combination with any of the following search terms and their corresponding abbreviations: positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and gamma-aminobutyric acid (GABA).Results: Altered functional connectivity in the cerebellum and cerebello-thalamico-cortical circuitry is a prevalent finding in functional imaging studies. Reports from structural imaging studies are less consistent, and there is no clear evidence for cerebellar neurodegeneration. However, diffusion tensor imaging robustly points toward microstructural cerebellar changes. Radiotracer imaging suggests that the dopaminergic axis is largely preserved in ET. Similarly, measurements of nigral iron content and neuromelanin are unremarkable in most studies; this is in contrast to Parkinson's disease (PD). PET and MRS studies provide limited evidence for cerebellar and thalamic GABAergic dysfunction.Conclusions: There is robust evidence indicating that the cerebellum plays a key role within a multiple oscillator tremor network which underlies tremor genesis. However, whether cerebellar dysfunction relies on a neurodegenerative process remains unclear. Dopaminergic and iron imaging do not suggest a substantial overlap of ET with PD pathophysiology. There is limited evidence for alterations of the GABAergic neurotransmitter system in ET. The clinical, demographical, and genetic heterogeneity of ET translates into neuroimaging and likely explains the various inconsistencies reported.

scholarly journals GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness

2019 ◽  
Author(s):  
Jordan D. Chamberlain ◽  
Holly Gagnon ◽  
Poortata Lalwani ◽  
Kaitlin E. Cassady ◽  
Molly Simmonite ◽  
...  
Keyword(s):  
Older Adults ◽  
Visual Cortex ◽  
Magnetic Resonance ◽  
Aminobutyric Acid ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Younger Adults ◽  
Inhibitory Neurotransmitter ◽  
Neural Representations ◽  
Age Related

AbstractAge-related neural dedifferentiation – reduced distinctiveness of neural representations in the aging brain– has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults predicted individual differences in neural distinctiveness even after controlling for gray matter volume and age. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.Significance StatementNeural representations in the ventral visual cortex are less distinguishable in older compared to younger humans, and this neural dedifferentiation is associated with age-related cognitive deficits. Animal models suggest that reductions in the inhibitory neurotransmitter gamma aminobutyric acid (GABA) may play a role. To investigate this hypothesis, we combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in a study of the human ventral visual cortex. We observed reduced distinctiveness of neural patterns and reduced GABA levels in older compared to younger adults. Furthermore, older adults with higher GABA levels tended to have more distinctive neural representations. These findings suggest that reduced GABA levels contribute to age-related declines in neural distinctiveness in the human ventral visual cortex.

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