Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm

Autor: Manfred Klöbl, D. Pacher, Vera Ritter, Melisande E. Konadu, Rene Seiger, Godber M Godbersen, Siegfried Trattnig, Benjamin Spurny, Sebastian Klug, Rupert Lanzenberger, Thomas Vanicek, Wolfgang Bogner, Murray B. Reed, Gregor Gryglewski, Jakob Unterholzner, Leo Silberbauer
Rok vydání: 2021
Předmět:
Adult
Male
medicine.medical_specialty
Magnetic Resonance Spectroscopy
Cognitive Neuroscience
Glutamic Acid
Hippocampus
Serotonergic
behavioral disciplines and activities
050105 experimental psychology
lcsh:RC321-571
Young Adult
GABA
03 medical and health sciences
0302 clinical medicine
Double-Blind Method
Internal medicine
medicine
Humans
SSRI
Learning
0501 psychology and cognitive sciences
Longitudinal Studies
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
gamma-Aminobutyric Acid
Serotonin transporter
5-HT receptor
biology
business.industry
Putamen
05 social sciences
Glutamate receptor
Association Learning
Brain
Magnetic Resonance Imaging
MRSI
Endocrinology
Neurology
biology.protein
GABAergic
Female
Serotonin
Glutamate
business
Photic Stimulation
Selective Serotonin Reuptake Inhibitors
030217 neurology & neurosurgery
Zdroj: NeuroImage, Vol 232, Iss, Pp 117913-(2021)
ISSN: 1053-8119
Popis: Impaired cognitive flexibility represents a widespread symptom in psychiatric disorders, including major depressive disorder (MDD), a disease, characterized by an imbalance of neurotransmitter concentrations. While memory formation is mostly associated with glutamate, also gamma-Aminobutyric acid (GABA) and serotonin show attributions in a complex interplay between neurotransmitter systems. Treatment with selective serotonin reuptake inhibitors (SSRIs) does not solely affect the serotonergic system but shows downstream effects on GABA- and glutamatergic neurotransmission, potentially helping to restore cognitive function via neuroplastic effects. Hence, this study aims to elaborate the effects of associative relearning and SSRI treatment on GABAergic and glutamatergic function within and between five brain regions using magnetic resonance spectroscopy imaging (MRSI). In this study, healthy subjects were randomized into four groups which underwent three weeks of an associative relearning paradigm, with or without emotional connotation, under SSRI (10mg escitalopram) or placebo administration. MRSI measurements, using a spiral-encoded, 3D-GABA-edited MEGA-LASER sequence at 3T, were performed on the first and last day of relearning. Mean GABA+/tCr (GABA+ = GABA + macromolecules; tCr = total creatine) and Glx/tCr (Glx = glutamate + glutamine) ratios were quantified in a ROI-based approach for the hippocampus, insula, putamen, pallidum and thalamus, using LCModel. A total of 66 subjects ((37 female, mean age ± SD = 25.4±4.7) for Glx/tCr and 58 subjects (32 female, mean age ± SD = 25.1±4.7) for GABA+/tCr were included in the final analysis. A significant measurement by region and treatment (SSRI vs placebo) interaction on Glx/tCr ratios was found (pcor=0.017), with post hoc tests confirming differential effects on hippocampus and thalamus (pcor=0.046). Moreover, treatment by time comparison, for each ROI independently, showed a reduction of hippocampal Glx/tCr ratios after SSRI treatment (puncor=0.033). No significant treatment effects on GABA+/tCr ratios or effects of relearning condition on any neurotransmitter ratio could be found. Here, we showed a significant SSRI- and relearning-driven interaction effect of hippocampal and thalamic Glx/tCr levels, suggesting differential behavior based on different serotonin transporter and receptor densities. Moreover, an indication for Glx/tCr adaptions in the hippocampus after three weeks of SSRI treatment could be revealed. Our findings are in line with animal studies reporting glutamate adaptions in the hippocampus following chronic SSRI intake. Due to the complex interplay of serotonin and hippocampal function, involving multiple serotonin receptor subtypes on glutamatergic cells and GABAergic interneurons, the interpretation of underlying neurobiological actions remains challenging.
Databáze: OpenAIRE
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