Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo 1H MRS study.
OBJECTIVE
While the pathophysiology of bipolar disorder (BD) remains to be elucidated, postmortem and neuroimaging studies have suggested that abnormalities in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the levels of specific brain chemicals of interest measured with proton magnetic resonance spectroscopy ((1)H MRS) in medication-free BD subjects and age- and gender-matched healthy controls. We hypothesized that BD subjects would present abnormal cellular metabolism within the DLPFC, as reflected by lower N-acetyl-aspartate (NAA) and creatine + phosphocreatine (Cr + PCr).


METHODS
Thirty-two medication-free BD subjects (33.8 +/- 10.2 years) and 32 matched controls (33.8 +/- 9.0 years) underwent a short echo-time (TE = 30 ms) (1)H MRS. An 8-cm(3) single voxel was placed in the left DLPFC, and individual concentrations of NAA, Cr + PCr, choline-containing compounds (GPC + PC), myo-inositol, and glutamate were obtained, using the water signal as an internal reference.


RESULTS
BD subjects had lower Cr + PCr [F((1,62)) = 5.85; p = 0.018; one-way analysis of variance (ANOVA)] and lower GPC + PC [F((1,62)) = 5.79; p = 0.019; one-way ANOVA] levels in the left DLPFC. No significant differences were observed for other brain metabolites.


CONCLUSIONS
These findings provide further evidence that the pathophysiology of BD involves impairment in the DLPFC. Our findings can be interpreted as evidence for reduced cellular energy and phospholipid metabolism, consistent with the hypothesis of mitochondrial dysfunction in BD.
Frey
Benício N
BN
MOOD-CNS Program, Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, TX 78229, USA. benicio.frey@gmail.com
Stanley
Jeffrey A
JA
Nery
Fabiano G
FG
Monkul
E Serap
ES
Nicoletti
Mark A
MA
Chen
Hua-Hsuan
HH
Hatch
John P
JP
Caetano
Sheila C
SC
Ortiz
Oswaldo
O
Kapczinski
Flávio
F
Soares
Jair C
JC
D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives; D001714:Bipolar Disorder / Q000473:pathology*; D016022:Case-Control Studies; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010725:Phosphocreatine / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology*; D011522:Protons; D012720:Severity of Illness Index
D010743:Phospholipids; D011522:Protons; D010725:Phosphocreatine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine