Wednesday journal club - Exploring the Impact of Low-Dose Oral Ketamine Treatment on EEG Power Spectra in Major Depressive Disorder with Chronic Suicidality

Major Depressive Disorder (MDD) represents a significant global health burden, with a heightened risk of chronic suicidality among affected individuals. Novel treatment approaches, such as ketamine, have garnered attention due to their potential to alleviate depressive symptoms and reduce suicidality rapidly. This study delves into the neurophysiological effects of low-dose oral ketamine treatment by investigating changes in Electroencephalogram (EEG) power spectra. Understanding the neurobiological underpinnings of ketamine's action through EEG analysis holds promise for elucidating its therapeutic mechanisms and guiding the development of more effective interventions for MDD and associated chronic suicidality.

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Introduction:

The study explores the effects of long-term, low-dose oral ketamine treatment on EEG (Electroencephalogram) power spectra in adults diagnosed with Major Depressive Disorder (MDD) and chronic suicidality. It is known that individuals with MDD are at a higher risk of suicide, making this an important area of research. The authors aim to investigate whether ketamine treatment has a measurable impact on EEG signals and if these changes correlate with improvements in clinical measures of depression, anxiety, and suicidality.

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Methods:

The study took place at the Thompson Institute between August 2018 and November 2019 and involved 32 participants who completed the trial. Participants received six weeks of flexible-dose oral ketamine treatment, followed by a four-week follow-up phase without treatment. The study included a range of clinical, neurophysiological, neuroimaging, and biochemical measures, but for this analysis, only EEG recordings and two clinical scales were used.

The primary clinical outcome measure was the reduction in suicidality assessed by the Beck Scale for Suicide Ideation (BSS). Secondary clinical measures included the Depression Anxiety Stress Scale (DASS-21). EEG data was recorded during resting-state conditions, and spectral analysis was performed to examine changes in power across different frequency bands (theta, alpha, low-beta, high-beta).

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Results:

The study found significant changes in EEG power spectra in response to ketamine treatment. Notably, there was a decrease in alpha band power at the centro-parietal region between pretreatment and posttreatment, followed by an increase between posttreatment and follow-up. Additionally, alpha band power increased at the temporal region between posttreatment and follow-up.

Theta band power showed significant changes between posttreatment and follow-up, with increases in power at the temporal and centro-parietal regions and a decrease at the occipital region. However, the timing of these changes suggests that the effects of ketamine may be transient.

Low-beta band power increased at the occipital region and decreased at the temporal region between posttreatment and follow-up. High-beta band power did not show significant changes.

What do they all mean? Well, let’s talk about band power a bit here. 

EEG power bands refer to specific frequency ranges of brainwave activity measured using an electroencephalogram (EEG). These bands are named after Greek letters, and each of them is associated with different mental states, cognitive processes, and functions. Here's an explanation of each EEG power band:

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Delta (δ) Waves (0.5-4 Hz):

• Delta waves are the slowest brainwaves and are typically observed in deep sleep stages (slow-wave sleep).
• They are associated with restorative processes, physical healing, and unconscious functions.
• An excess of delta activity during wakefulness may indicate brain damage or certain neurological conditions.

Theta (θ) Waves (4-8 Hz):

• Theta waves are commonly seen during light sleep stages, meditation, and states of deep relaxation.
• They are also associated with creativity, daydreaming, and access to the subconscious mind.
• Excessive theta activity may occur in people with attention deficit disorders.

Alpha (α) Waves (8-13 Hz):

• Alpha waves are prominent when a person is awake but relaxed and not highly focused on external stimuli.
• They are often observed when closing one's eyes, daydreaming, or during meditation.
• An increase in alpha activity may indicate a calm and alert mental state.

Beta (β) Waves (13-30 Hz):

• Beta waves are associated with active, alert, and engaged mental states.
• They are prevalent when a person is awake, alert, and focused on tasks.
• Higher beta frequencies may indicate stress, anxiety, or intense cognitive processing.

Low Beta (13-20 Hz):

• Low beta waves are in the lower range of beta frequencies and are associated with normal, everyday waking consciousness.
• They are often seen during problem-solving, decision-making, and active mental engagement.

High Beta (20-30 Hz):

• High beta waves represent higher-frequency beta activity.
• They are often associated with heightened alertness, cognitive control, and stress.
• Excessive high beta activity may be linked to anxiety disorders.

Gamma (γ) Waves (30-100 Hz):

• Gamma waves are the fastest brainwaves and are associated with high-level cognitive functions.
• They are thought to play a role in perception, memory, and information processing.
• Abnormal gamma wave activity has been studied in conditions like schizophrenia.
  

Discussion:

The study's findings provide valuable insights into the impact of low-dose oral ketamine treatment on EEG power spectra in individuals with MDD and chronic suicidality. The observed changes in alpha, theta, and low-beta bands suggest that ketamine may have neurophysiological effects on brain activity, particularly in regions associated with depressive symptoms and emotional regulation.

It is essential to note that the correlation analysis indicated that changes in EEG power spectra did not strongly correlate with improvements in the primary clinical outcome measure (BSS). However, there were significant correlations between changes in EEG and secondary clinical measures (DASS-21), suggesting that EEG changes may relate more to anxiety and stress symptoms.

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Limitations:

The study acknowledges several limitations, including the relatively small sample size and the absence of control groups. The participants were also taking various psychotropic medications, which could have confounded the results. Additionally, the study did not explore differences between responders and non-responders to ketamine treatment, which could provide valuable insights.

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Conclusion:

In conclusion, this study demonstrates that low-dose oral ketamine treatment can lead to significant changes in EEG power spectra in individuals with MDD and chronic suicidality. While the correlation with the primary clinical outcome was weak, the relationships with secondary clinical measures suggest that EEG may be a valuable tool for assessing the impact of ketamine on anxiety and stress symptoms. Future research with larger sample sizes and controlled designs is needed to further elucidate the role of EEG as a potential biomarker for ketamine treatment response in depression and suicidality.

Journal Club Rating: This study provides valuable insights into the effects of ketamine on EEG in individuals with MDD and suicidality, with important implications for future research and treatment approaches. However, the limitations and the need for further investigation into the clinical significance of EEG changes should be considered.

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