title: Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders.
abstract: OBJECTIVE
  We aimed to determine the effect of an open-label 8 week Vitamin D3 supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D3 supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD).
  
  
  METHODS
  The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6-17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D3 (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D3 supplementation.
  
  
  RESULTS
  Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=-3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=-2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14).
  
  
  CONCLUSIONS
  Following an 8 week open label trial with Vitamin D3, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry.
authors.affiliation: 1 Center for Comparative NeuroImaging, University of Massachusetts Medical School , Worcester, Massachusetts.|2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Elif M
authors.initials: EM
authors.lastname: Sikoglu
authors.affiliation: 1 Center for Comparative NeuroImaging, University of Massachusetts Medical School , Worcester, Massachusetts.|2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.|4 Office Médico-Pédagogique, Department of Psychiatry, University of Geneva School of Medicine , Geneva, Switzerland .
authors.forename: Ana A Liso
authors.initials: AA
authors.lastname: Navarro
authors.affiliation: 2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Debra
authors.initials: D
authors.lastname: Starr
authors.affiliation: 2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Yael
authors.initials: Y
authors.lastname: Dvir
authors.affiliation: 5 Department of Pediatrics, University of Massachusetts Medical School, Worcester , Massachusetts.
authors.forename: Benjamin Udoka
authors.initials: BU
authors.lastname: Nwosu
authors.affiliation: 1 Center for Comparative NeuroImaging, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Czerniak
authors.affiliation: 1 Center for Comparative NeuroImaging, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Rogan
authors.affiliation: 2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Castro
authors.affiliation: 6 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine , Baltimore, Maryland.|7 F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.affiliation: 2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.|5 Department of Pediatrics, University of Massachusetts Medical School, Worcester , Massachusetts.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Frazier
authors.affiliation: 1 Center for Comparative NeuroImaging, University of Massachusetts Medical School , Worcester, Massachusetts.|2 Child and Adolescent NeuroDevelopment Initiative, University of Massachusetts Medical School , Worcester, Massachusetts.|3 Department of Psychiatry, University of Massachusetts Medical School , Worcester, Massachusetts.|8 Department of Radiology, University of Massachusetts Medical School , Worcester, Massachusetts.
authors.forename: Constance M
authors.initials: CM
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000339:Affect / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D002762:Cholecalciferol / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002762:Cholecalciferol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid