A Probiotic Intervention to Prevent Relapse Following Hospitalization for Mania

Primary Aim 1. To determine if adjunctive probiotic administration can reduce relapse for participants first hospitalized for mania. Hypothesis: Participants receiving adjunctive probiotic microorganisms vs. adjunctive placebo will have a lower rate of relapse as defined by a re-hospitalization (e.g., admission to an inpatient unit) during the 24 week study period.

Secondary Outcomes. The number of new mood episodes, the severity of psychiatric symptoms, and changes in cognitive scores over the 24 week study period will be evaluated.

Exploratory Aim 1. To study the effect of probiotic therapy in lowering the levels of inflammatory markers following an acute episode of mania. Hypothesis: Participants receiving adjunctive probiotic microorganisms vs. adjunctive placebo will have reduced levels of antibodies to casein, gliadin, and the NMDA receptor, and reduced levels of C-Reactive protein and the cytokine TNF alpha following 24 weeks of probiotic therapy.

Exploratory Aim 2. To evaluate changes in the gut microbiota following probiotic administration. Hypothesis: Probiotic administration will enrich the gut microbiota of participants with the given microorganisms and these changes may correlate to changes in the peripheral inflammatory markers being measured.

Inclusion criteria

• Capacity for written informed consent
• Currently (or within the last 3 weeks) admitted to inpatient hospital for symptoms of mania.
• Primary Axis I diagnosis (DSM-5) at time of admission of bipolar I (single manic episode, most recent episode manic, or most recent episode mixed) OR schizoaffective disorder, bipolar type (manic or mixed state).
• Proficient in the English language.
• Available to attend follow-up visits.

Exclusion criteria

• Substance- or medically-induced symptoms of mania at time of assessment.
• HIV infection or other immunodeficiency condition (such as receiving cancer chemotherapy).
• A serious medical condition that affects brain or cognitive functioning (e.g., epilepsy, serious head injury, concussion involving loss of consciousness, brain tumor, or other neurological disorder). Note that Hepatitis-C is not an exclusion criterion unless the participant has an acute infection.
• Poorly controlled comorbid medical condition.
• Major surgery in the last year.
• History of weight loss surgery.
• Diagnosis of Intellectual Disability or history of severe learning disorder.
• Diagnosis of alcohol or substance use disorder (moderate/severe) according to DSM-5 criteria within the last 3 months, or has a positive drug toxicity screen proximate to the time of recruitment.
• History of IV drug use.
• Participated in any investigational drug trial in the past 30 days.
• Abnormal electrolyte levels.
• AST and ALT > 3 times upper limit of normal.
• Pregnant, breastfeeding, or planning to become pregnant during the study period.
• Documented celiac disease (as such persons should be on a gluten-free diet as this is the standard care). Of note, we are not limiting the study to individuals with elevated levels of gliadin or casein antibodies as we intend to look at these levels as a predictor of response.