Psychiatric Times.
No. 9
Utilization of MRS to Identify Neurochemical Abnormalities in Patients With Bipolar Disorder
By Serap Monkul, M.D., and Jair C. Soares, M.D.
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August 1, 2004
Dr. Monkup is a postdoctoral fellow in the division of mood and anxiety disorders in the department of psychiatry at the University of Texas Health Sciences Center at San Antonio.
Dr. Soares is chief of the division of mood and anxiety disorders in the department of psychiatry at the University of Texas Health Sciences Center at San Antonio.
Bipolar disorder is associated with altered brain chemistry in a number of regions, mainly the DLPFC, basal ganglia, hippocampus and anterior cingulate. The NAA levels in the DLPFC are decreased in patients with BD. It is not clear whether such an abnormality may precede illness onset, or to what extent it may reflect aberrant neurodevelopmental mechanisms, or whether it is related to progressive neuronal loss during the disease process.
Decreased NAA levels may reduce the transfer of acetyl groups required for myelin formation and/or maintenance (Chakraborty et al., 2001). Moreno et al. (2001) demonstrated that NAA synthesis is coupled to energetic (glucose) metabolism using in vivo 13C-MRS and [1-13C] glucose infusion. Abnormal brain energy metabolism is also suggested by 31P-MRS findings, such as decreased phosphocreatine (PCr) and intracellular pH (Kato et al., 1994, 1993). A mitochondrial dysfunction hypothesis for the pathophysiology of BD has also been proposed (Konradi et al., 2004).
Studying treatment effects on the neurochemistry of BD is an intriguing area of research (Soares, 2002). The findings of the studies reviewed here show that lithium(Drug information on lithium) increases total brain NAA and decreases mI in the anterior cingulate and right frontal lobe, whereas it does not affect the Cho resonance in the parietal lobes. Divalproex also appears to have an effect on the activity of the intracellular phosphoinositol cycle similar to lithium.
Treatment with GABAergic medications increases prefrontal GABA, while treatment with SSRIs is possibly associated with increased occipital cortex GABA concentrations and with a decrease in Cho in the anterior cingulate cortex.
These findings are preliminary and need replication, but they are important. They reflect cellular metabolism and membrane turnover, upon which many essential neuronal functions, such as neurotransmission and second- messenger cascades, are dependent. The application of in vivo MRS technology to the study of the pathophysiology of BD and the mechanisms of action of mood stabilizers is a new field of research. Currently, this is primarily a research tool, but as research evolves and the mechanisms involved are elucidated, it is expected that such tools will be of relevance for diagnosing and monitoring the effects of various treatments.
Acknowledgement
Our work on this field has been partly supported by MH 01736, the National Alliance for Research on Schizophrenia and Depression, Dana Foundation, the American Foundation for Suicide Prevention, the U.S. Department of Veterans Affairs, the Krus Endowed Chair in Psychiatry (UTHSCSA), and the UTHSCSA GCRC and its imaging core (M01-RR-01346).
Dr. Monkup is a postdoctoral fellow in the division of mood and anxiety disorders in the department of psychiatry at the University of Texas Health Sciences Center at San Antonio.
Dr. Soares is chief of the division of mood and anxiety disorders in the department of psychiatry at the University of Texas Health Sciences Center at San Antonio.
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