Increased thalamic N-acetylaspartate in male patients with familial bipolar I disorder

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

“…This would suggest that Cr may not be a stable resonance to be used as an internal standard or reference ratio in bipolar depression research. This certainly warrants further investigation as the current literature in bipolar disorder, although different in methodology, mood state, and brain region, has reported increased creatine (Deicken et al, 2001;Michael et al, 2003Ftrend, Hamakawa et al, 1999Fmen only), decreased creatine (Deicken et al, 2003), or no change in creatine (Hamakawa et al, 1998;Friedman et al, 2004;Cecil et al, 2002;Brambilla et al, 2005;Frey et al, 2005).…”

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

“…In contrast with the majority of published MRS research on bipolar disorder, one study by Deicken et al 31 reported increased thalamic NAA in male bipolar subjects compared to normal controls. However, all but two of the bipolar subjects in this study were taking maintenance medications such as lithium and divalproex, which may have contributed to the observed increases in NAA.…”

“…A number of studies have demonstrated that at therapeutically relevant concentrations, lithium is a potent, noncompetitive inhibitor of inositol-1-phosphatase, an enzyme that normally serves to recycle inositol sugar phosphates back into the free inositol pool. This inhibition leads to an accumulation of inositol-1-phosphate (a component of the PME signal in 31 P MRS) and a simultaneous decrease in levels of mI. [96][97][98] Since sufficient supplies of mI are necessary both for the re-synthesis of certain membrane components and to maintain the phosphoinositide intracellular signaling system, it has been suggested that lithium achieves its effects through this depletion of the free inositol pool.…”

“…Although the confounding effects of lithium cause difficulty in the interpretation of mI levels in bipolar patients, it may yet be argued that elevated mI levels suggest an increase in membrane breakdown and inhibition of membrane metabolism in bipolar disorder that may be caused by mitochondrial dysfunction. 31 P MRS studies of PME levels in bipolar subjects have indicated that some abnormalities in bipolar membrane metabolism may be state dependent, specifically differing during periods of euthymia, mania, and depression (Tables 9 and 10). Similar to the multicomponent Cho signal, the PME signal observed by 31 P MRS is the combined product of multiple compounds.…”

“…However, all but two of the bipolar subjects in this study were taking maintenance medications such as lithium and divalproex, which may have contributed to the observed increases in NAA. 24,31 Furthermore, since positron emission tomography (PET) studies have reported increases in the concentration of thalamic monoaminergic synaptic terminals in bipolar patients, 32,33 it is possible that Deicken et al's 31 observations of increased thalamic NAA were due to increased synaptic density rather than metabolic abnormality. Similarly, with regard to the findings of Ongur et al 34 of regionally reduced glial cell number and density in patients with bipolar disorder, it is also possible that Deicken et al's 31 findings may be due to glial cell hypoplasia in the thalamus.…”