Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

Change from baseline to week 12 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).

Change from baseline to week 12 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.

Change from baseline to week 12 of insulin resistance measured using the homeostatic model assessment of insulin resistance (HOMA-IR) using fasting blood glucose and insulin levels.

Change from baseline to week 12 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 30-210; a higher score indicates a higher level of psychotic symptoms.

Change from baseline to week 12 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.

Change from baseline to week 12 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60. A higher score indicates a more severe illness.

Change from baseline to week 12 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.

Change from baseline to week 12 in participant body weight in kilograms, as measured using a standing scale.

Change from baseline to week 12 in fasting Hemoglobin A1c level.

Change from baseline to week 12 in fasting triglyceride levels.

Change from baseline to week 12 in fasting LDL levels.

Change from baseline to week 12 in fasting HDL levels.

Change from baseline to week 12 in fasting hs-CRP levels.

Change from baseline to week 12 in GABA concentration measured by proton magnetic resonance spectroscopy.

Change from baseline to week 12 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.

Change from baseline to week 12 in brain GSH measured by proton magnetic resonance spectroscopy.

Changes from baseline to week 12 in PCr concentration as measured by in vivo 31P-MRS.

Change from baseline to week 12 in pH as measured by in vivo 31P MRS.

Change from baseline to week 12 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS.

Change from baseline to week 12 from baseline to week 12 in adverse events.

Change from baseline to week 12 from baseline to week 12 in Hamilton Anxiety Rating Scale (HAM-A) total score. Scores range from 0 - 56; a higher score indicates a higher level of anxiety.

Change from baseline to week 12 in Depression Anxiety Stress Scales (DASS-42) Stress Subscale score. Scores range from 0-42; a higher score indicates a higher level of stress.

Change from baseline to week 12 in Matrics Consensus Cognitive Battery (MCCB) Total Score. Scores range from 0.00% - 100.00%; a higher score indicates higher cognition.

Change from baseline to week 12 in Global Functioning Scale (GFS) - Social and Role total score. Scores range from 6-60; a lower score indicates worse social and role functioning.

Change from baseline to week 12 in blood and saliva cf-mtDNA levels.

Change from baseline to week 12 in blood and saliva GDF15 levels.

Change from baseline to week 12 in blood NAD/NADH+ ratio.

Change from baseline to week 12 in blood GSH/GSSH ratio.

Change from baseline to week 12 in World Health Organization Disability Assessment Schedule (WHODAS) scale. Scores range from 0-144. A higher score indicates greater dysfunction and disability in major life domains.

Change from baseline to week 12 in World Health Organization Quality of Life (WHOQOL) scale. Scores range from 1-130. A lower score indicates lower perceived quality of life.

Change from baseline to week 12 in Extrapyramidal Symptom Rating Scale (ESRS) total score. Scores range from 0-102; a higher score indicates more severe symptoms.

Change from baseline to week 12 in Pittsburgh Sleep Quality Index (PSQI) total score. Scores range from 0-21; a higher score indicates worse sleep quality.

Change within network positive correlations and between network negative correlations from baseline to week 12.

Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas from baseline to week 12.

Change in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas from baseline to week 12.

Change in fractional anisotropy (FA), a scalar measure of diffusivity, of water in the brain assessed by DTI at 3T from baseline to week 12. FA values range from 0 (isotropic, meaning diffusion is equally restricted in 3D space) to 1 (anisotrophic, meaning that diffusion is completely restricted to a single direction).