Ketogenic Intervention in Depression

The WHO-5 (World Health Organization-Five Well-Being Index) is a self-assessment questionnaire used to measure subjective well-being and mental health. It was developed by the World Health Organization (WHO) and consists of five statements related to positive mood, vitality, and general interest in life. The five statements in the WHO-5 questionnaire are as follows:

I have felt cheerful and in good spirits. I have felt calm and relaxed. I have felt active and vigorous. I woke up feeling fresh and rested. My daily life has been filled with things that interest me. Respondents are asked to rate each statement based on how they have felt over the past two weeks, using a six-point Likert scale ranging from "at no time" to "all of the time." The scores for each item are summed, resulting in a total score ranging from 0 to 25. Higher scores indicate better well-being

Hamilton Depression Scale consists of 17 items that cover various symptoms of depression, including depressed mood, guilt, suicidal thoughts, insomnia, agitation, weight loss, and somatic symptoms. Each item is rated on a scale from 0 to 4 or 0 to 2, depending on the item, with higher scores indicating more severe symptoms.

The scale is typically administered by a trained healthcare professional who interviews the individual and rates their symptoms based on their observations and the individual's self-report. The rater assesses the severity of each symptom and determines the appropriate score for each item.

The total score on the Hamilton Depression Scale can range from 0 to 52, with higher scores indicating greater severity of depression. However, it is important to note that the interpretation of the total score requires clinical judgment and consideration of the individual's overall presentation and context.

changes in fasting ketone levels.

changes in fasting glucose levels.

The Patient Health Questionnaire-9 used bi-weekly to asses changes in degree of depression (intensity and severity).

Each item in the PHQ-9 is rated on a scale from 0 to 3, reflecting the frequency of the symptoms over the past two weeks. The response options are "not at all" (0), "several days" (1), "more than half the days" (2), and "nearly every day" (3). The scores for each item are summed to obtain a total score ranging from 0 to 27.

The interpretation of PHQ-9 scores is as follows:

0-4: None to minimal depression 5-9: Mild depression 10-14: Moderate depression 15-19: Moderately severe depression 20 and above: Severe depression

changes in daily glucose and ketone levels.

Changes in metabolic blood panel will be assessed at in lab visits (eg. Baseline, Week 6, and Week 12)

Changes in both Systolic and Diastolic blood pressure will be measured at each lab visit (eg. Baseline, Week 6, and Week 12).

Recording: The systolic and diastolic pressures are recorded in millimeters of mercury (mmHg). For example, a reading of "120/80 mmHg" indicates a systolic pressure of 120 mmHg and a diastolic pressure of 80 mmHg.

The NIH Toolbox includes a comprehensive set of measures across various domains, including:

Cognition: executive function, attention, memory, language, processing speed, and working memory. These measures help evaluate cognitive abilities and identify potential cognitive impairments.

Emotion: emotional well-being, social functioning, and psychological distress. It provides tools to assess symptoms of depression, anxiety, and positive affect, as well as social functioning and quality of life.

Motor: motor function, dexterity, strength, coordination, and balance. These assessments are designed to evaluate both fine and gross motor skills and detect any motor impairments or changes over time.

Sensation: auditory, visual, and somatosensory abilities. These measures help evaluate sensory perception, discrimination, and thresholds.

During whole brain EPI data acquisition, participants will be presented with words and pictures and asked to make judgements about the stimuli, such as indicating whether a particular stimulus (e.g., face-name association, word, number, or letter) has been previously presented, if a presented stimulus is a city or mountain scene, the direction an arrow is pointing (left or right), if a pair of stimuli match (e.g., faces with neutral or emotional expressions; word with a face). Behavioral responses will be recorded with an MRI compatible button box.

Changes in cortical thickness, brain volume, and functional connectivity for pre- intervention and post intervention testing days.

Whole brain echo-planar imaging (EPI) volumes sensitive to the BOLD signal will be acquired. Images will be re-aligned, un-warped, and normalized. Confounding effects of white matter, CSF signal, and head motion will be regressed from the functional time series, followed by bandpass filtering, linear detrending and smoothing, and whole brain resting state networks will be identified (e.g., default mode network, salience network, etc).

Changes in lean body mass.

Changes in body mass index.

Changes in total body weight.