Examining Neurobiological Mechanisms Underlying the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder (BD)

The investigators aim to examine the effect of the ketogenic diet on brain activity, metabolism, and emotions in adults with Bipolar Disorder (BD).

The investigators hypothesize that a ketogenic diet will enhance levels of the ketone body β-Hydroxybutyrate (beta OHB), resulting in reduced mania/hypomania severity and predisposition to mania/hypomania in individuals with BD. To test this hypothesis in depth, the investigators will use a novel, multidisciplinary mechanistic study using multimodal neuroimaging, peripheral markers of mitochondrial metabolism, and participant-derived induced pluripotent stem cell (iPSC)-derived organoids.

Eligibility Criteria:
Inclusion Criteria:

All participants:

* 18-40 years of age
* Not following a ketogenic diet

BD hypomanic group (n=30):

* Meeting sex proportion: 50% female
* Meeting diagnosis proportion: 50:50% Bipolar I: Bipolar II (BDI:II) (Diagnostic and Statistical Manual of Mental Disorders 5; DSM-5)
* Score greater than 10 on the Young Mania Rating Scale score(YMRS)
* BD medications will be allowed as in our previous studies: any combination of atypical antipsychotics, lithium, antidepressants, anxiolytics (common in BD)

BD euthymic group (n=30):

* Meeting sex proportion: 50% female
* Meeting diagnosis proportion: 50:50% BDI:II (DSM-5)
* Score less than or equal to 10 on YMRS
* BD medications will be allowed as in our previous studies: any combination of atypical antipsychotics, lithium, antidepressants, anxiolytics (common in BD)

Healthy Control (HC) Group (n=30):

* Sex matched with BD groups
* No psychiatric history

Exclusion Criteria:

All participants:

* Not between 18-40 years of age
* History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report)
* Mini-Mental State Examination score (cognitive state) \<24
* Premorbid National Adult Reading Test Intelligent Quotient (NAART IQ) estimate\<85
* Visual disturbance: \<20/40 Snellen visual acuity
* History of alcohol/substance use disorder (SUD; all substances, including nicotine), and/or illicit substance use (except cannabis) over the last 6 months (SCID-5). Note: lifetime/present cannabis use (at non-abuse (\<3 times in the past month) and non SUD levels) will be allowed, given its common usage in BD and young adults. Cannabis SUD over the last 6 months will not be allowed. Urine tests on scan days will exclude current illicit substance use (except cannabis). Salivary alcohol tests on scan days will exclude intoxicated individuals
* MRI exclusion: metallic objects, e.g., surgical implants; claustrophobia; positive pregnancy test for females or self-report pregnancy
* Unable to understand English
* Conditions related to the pancreas, liver, thyroid or gallbladder.
* Taking anticoagulants and/or those with blood dyscrasias (illnesses) who have coagulation disorders (eg, hemophilia) because of the ketomojo finger stick blood tests
* Scoring 3 or higher on positive symptom factor questions on the Positive and Negative Syndrome Scale (PANSS) questionnaire (indicative of psychotic symptoms)
* Currently following a ketogenic diet
* Head circumference larger than 24 inches (62cm) and/or chest circumference larger than 55 inches (139 cm)

BD hypomanic group:

* Must be meeting sex proportions: not 50% female
* Must be meeting diagnosis proportions: not 50:50% BDI:II (DSM-5)
* Diagnosis of BD in a manic or euthymic episode
* Score 10 or lower on the Young Mania Rating Scale score(YMRS)
* Using psychotropic medications other than those allowed in inclusion criteria
* Does not have a smartphone with a) iOS version 12.0 or above, or b) Android version 8 and later to use with the Keto-Mojo app

BD euthymic group:

* Not meeting sex proportion: not 50% female
* Not meeting diagnosis proportion: not 50:50% BDI:II
* Diagnosis of BD in a depressive, hypomanic, or manic episode
* Score greater than 10 on YMRS
* Using psychotropic medications other than those allowed in inclusion criteria
* Does not have a smartphone with a) iOS version 12.0 or above, or b) Android version 8 and later to use with the Keto-Mojo app

Healthy Control (HC) Group

* Not sex-matched with BD groups
* Has psychiatric history