examining neurobiological mechanisms underlying the therapeutic effect of the ketogenic diet in bipolar disorder (bd)

Conditions: Bipolar Disorder

Summary: 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

Keywords: ketogenic diet magnetic resonance imaging