title: Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder.
abstract: Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Yuksel
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Du
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ravichandran
authors.affiliation: McLean Hospital, Belmont, MA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Goldbach
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Geisel School of Medicine, Dartmouth, NH, USA.
authors.forename: T
authors.initials: T
authors.lastname: Thida
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.|Key Laboratory of Biomedical Information Engineering of Education Ministry, Institute of Biomedical Engineering, Xi`an Jiaotong University, Xi`an, China.
authors.forename: P
authors.initials: P
authors.lastname: Lin
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Koc University, Department of Psychology, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Dora
authors.affiliation: McLean Hospital, Belmont, MA, USA.|George Washington University Medical School, Washington, DC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gelda
authors.affiliation: McLean Hospital, Belmont, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: O'Connor
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Bryn Mawr College, Bryn Mawr, PA.
authors.forename: S
authors.initials: S
authors.lastname: Sehovic
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gruber
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ongur
authors.affiliation: McLean Hospital, Belmont, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism*; D010775:Photic Stimulation
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase