Page 17 - JCBP-2-3

Journal of Clinical and
Basic Psychosomatics The antidepressant effect of ketamine

with DMN 2 weeks post-ketamine treatment. Remission treatment. While the α band showed initial changes in
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in depressive patients after ketamine treatment has been the early stages of treatment but returned to baseline
associated with increased functional connectivity between levels at treatment cessation, the θ and low-β bands
the sgACC and the supplementary motor area, as well exhibited significant changes after the end of treatment.
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as the dlPFC. Another study revealed that depression McMillan et al. combined MRI and EEG to investigate
remission was related to decreased functional connectivity the correlation mechanism between EEG and BOLD
between the sgACC and the right amygdala, a finding signals underlying the rapid-acting antidepressant effect of
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corroborated by a recent study. Nugent et al. reported ketamine. They found that low β and high γ power time
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decreased functional connectivity between the amygdala courses explained significant variance in the BOLD signal.
and the insula, as well as the temporal cortex, post- This finding suggested that the decreased sgACC BOLD
ketamine treatment, suggesting that ketamine could signal might be noise with no relation to the antidepressant
normalize this hyperactive signature of depression. response to ketamine.
Functional connectivity within the frontostriatal circuitry A recent EEG study revealed increased long-term
has also been associated with ketamine response. Decreased potentiation approximately 4 h after a single ketamine
functional connectivity within the frontostriatal circuitry infusion, suggesting that ketamine could accelerate neural
at baseline has been linked to subsequent improvements plasticity within the time frame of its antidepressant
in depressive symptoms, and frontostriatal connectivity effects. Sleep slow wave activity (SWA), measured using
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increased 2 days after a single ketamine infusion. In EEG, may be a marker of homeostatic sleep regulation as
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addition, increased frontostriatal connectivity was found well as synaptic plasticity. Evidence shows reduced SWA
to be associated with improvements in anhedonia. 29 in depressive patients. Duncan et al. observed increased
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As a pivotal hub of the epithalamus, the habenula SWA during the first non-rapid eye movement (REM)
directly connects with limbic structures and the basal episode post-ketamine treatment compared with baseline
ganglia, playing a crucial role in regulating emotion, in TRD patients. This alteration in SWA was significantly
reward, and motivation. Studies have reported that correlated with the changes in brain-derived neurotrophic
increased functional connectivity between the habenula factor (BDNF), a classical marker of neuronal plasticity,
and the right dlPFC is associated with an improved in patients who responded to ketamine. Another study
antidepressant response following a single ketamine revealed a relationship between a lower SWA ratio in
infusion. Furthermore, increased functional connectivity the non-REM period and the antidepressant effect of
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between the right habenula and the occipital-temporal ketamine. Rantamaki and Kohtala proposed the
cortex, as well as the para-hippocampal gyrus, has been coding, consolidation, and reorganization hypothesis of
linked to subjective mood improvement. 31 depression, considering changes in SWA and synaptic
strength as the underlying mechanisms of the rapid-acting
Relatively, few studies have employed task-based fMRI antidepressant effects of ketamine.
due to the stringent demands of research equipment.
However, a double-blind controlled trial investigated 4. Neurobiochemical markers
the influence of ketamine on cognitive and emotional Several neurobiochemical hypotheses explain the
processing in patients with TRD. This study applied antidepressant effect of ketamine. The most popular
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implicit and explicit facial recognition tasks to examine is the glutamatergic hypothesis, which has been the
how ketamine impacts brain activity. The results subject of extensive investigation. Moreover, evidence
indicated that the pattern of brain activity after ketamine from research testing the energy metabolism hypothesis,
infusion resembled that of the control group following a immunoinflammatory hypothesis, and neurotrophic
placebo infusion, suggesting that ketamine may act as hypothesis has provided valuable insights. This section
an antidepressant by normalizing brain function during presents a review of the relevant investigations on these
mood processing. four hypotheses.
3. Neuroelectrophysiological markers 4.1. Glutamatergic neurotransmitters

Neuroelectrophysiological changes associated with the Magnetic resonance spectroscopy (MRS) can be used to
antidepressant effects of ketamine can be detected using examine intracerebral glutamatergic levels. MRS studies
magnetoencephalography and electroencephalography have shown that the glutamate levels in the hippocampus,
(EEG), two technologies known for their high temporal PFC, and ACC are decreased in depressive patients. 40-42
resolution. EEG analysis revealed significant changes in In addition, glutamate levels in the ACC are significantly
the α, θ, and low-β frequency bands during ketamine correlated with anhedonia in patients. Milak et al.
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Volume 2 Issue 3 (2024) 4 doi: 10.36922/jcbp.2596