Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients.
OBJECTIVE
Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder.


METHODS
The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference.


RESULTS
Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites.


CONCLUSIONS
These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.
Sassi
Roberto B
RB
Division of Mood and Anxiety Disorders, Associate Professor of Psychiatry and Radiology, Krus Endowed Chair in Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Stanley
Jeffrey A
JA
Axelson
David
D
Brambilla
Paolo
P
Nicoletti
Mark A
MA
Keshavan
Matcheri S
MS
Ramos
Renato T
RT
Ryan
Neal
N
Birmaher
Boris
B
Soares
Jair C
JC
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002794:Choline / Q000032:analysis / Q000378:metabolism; D003401:Creatine / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism; D017397:Prefrontal Cortex / Q000737:chemistry* / Q000378:metabolism / Q000503:physiopathology; D012008:Recurrence
D010725:Phosphocreatine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline