Conduct randomized double-blind controlled trial (RCT), to examine the effects of vitamin D on cognitive performance in euthymic BD.

Bipolar disorder (BD) is a chronic mental disease related to recurrent episodes along with cognitive or functional decline. Comparing efficacy of pharmacological interventions targeting to treat cognitive deficit in BD is unexplored. The majority of the observational studies demonstrate a significant association between low serum vitamin D and compromised cognition in a wide range of neuropsychiatry diseases. Recent survey further revealed the high prevalence of hypovitamin D in BD. The effect of supplement and association between vitamin D and cognition in BD and the underlying mechanism is unclear.

The investigators will collect vitamin D levels and assess their association with cognition in a euthymic bipolar cohort (N=200) for screen. Then, the investigators estimate to recruit 120 of participants with cognitive deficits and combined vitamin D deficiency, to conduct a RCT. Participants will keep their usual treatment and will be randomized to receive either vitamin D supplement or a placebo for eight weeks. Cognitive test, adverse side effect, mood status and blood 25(OH)D levels and biomarkers will be measured before and after intervention.

Inclusion Criteria:

1. Patients who diagnosed with BD-I based on the Diagnostic and Statistical Manual (DSM-IV) criteria are consecutively referred by board-certified psychiatrists in Taipei City Hospital, Songde branch.
2. Age of participants should range from 20 to 65 years old.
3. No history of vitamin D supplementation within three months before the study.
4. The BD patients in their euthymic state (both Hamilton Depression Rating Scale and Young Mania Rating Scale ≤ 8) and no change of their psychoactive medications in recent three months.

Exclusion Criteria:

1. With known substance use disorder (except nicotine use disorder)
2. With any disorder with known neurological symptoms or complications (ex. brain injury, stroke or brain lesions)
3. Comorbid with schizophrenia spectrum disorders
4. With active physical condition (such as renal impairment, hepatic failure…) or pregnancy
5. Inability to complete the standard assessment or incapability of providing informed consent

individual patient data can be sharing with de-identification process after asking

A pharmacist will prepare the dosing of solubilized vitamin D3 and also identical appearance of placebo according to a randomized block schedule. Patients and researchers were blinded to treatment assignment.