Trait-related alterations of N-acetylaspartate in euthymic bipolar patients: A longitudinal proton magnetic resonance spectroscopy study

Abstract

Background Neurochemical changes are responsible for bipolar disorder (BD) pathophysiology. Despite current progress in BD research, mood- and trait-related alterations in BD continue to elicit further investigation. Methods In this study, we report a longitudinal proton magnetic resonance spectroscopy study evaluating dorsomedial prefrontal cortex (DMPFC) metabolites N-acetylaspartate (NAA), creatine plus phosphocreatine (total creatine [tCr]), phosphorylcholine plus glycerophosphocholine, myo-inositol, and glutamate plus glutamine levels of manic and euthymic adult BD type I patients (n=48) treated with standard antimanic medicines, compared to matching healthy controls (n=44). Results DMPFC NAA values and NAA/tCr ratio were significantly lower in euthymic BD patients when compared with healthy controls with similar levels of other metabolites in all groups, indicating a trait-related NAA abnormality in euthymic BD patients. Limitations Limitations of our study include a relatively low (1.5 tesla) magnetic resonance field strength and variable drugs administered to achieve euthymia despite the best efforts to standardize the open fashion treatment. Conclusions Our study contributes to the integrating models of trait-related metabolite alterations observed in euthymia since NAA is considered as a marker of neuronal viability and mitochondrial energy metabolism. In light of supporting and conflicting results reported previously, future studies with longitudinal designs and larger patient groups are warranted to better define both state- and trait-related cerebral metabolic alterations associated with BD pathophysiology.

Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder

“…Reduced NAA/tCr ratios have been reported in diverse cases, such as patients with Alzheimer’s disease, euthymic bipolar disorder, or men with recreational cannabis usage [ 70 – 72 ]. Interestingly, increased NAA/tCr levels have rarely been reported.…”

Zusammenhang zwischen der Einnahme von Lithium und neuroradiologischen Veränderungen bei der bipolar affektiven Störung: Gibt es Hinweise auf ein klinisches Ansprechen?

“…Bei Betrachtung der verschiedenen einzelnen Metaboliten gibt es Hinweise, dass der Zustand einer Euthymie in einzelnen zentralnervösen Regionen nicht zu einer Normalisierung der jeweiligen Konzentrationen zu führen scheint. Darauf weisen beispielsweise neueste longitudinale Daten hin, welche im Vergleich zu gesunden Kontrollen erniedrigte NAA-Konzentrationen bei euthymen Patienten im dorsomedialen PFC aufzeigen [59] Spezifische Veränderungen unter Lithium Relativ betrachtet sind die Daten zum Wirkstoff Lithium sehr konsistent. Die lithiumassoziierten Veränderungen können insgesamt als normalisierend beschrieben werden.…”

Neurophysiological effects of multiple mood episodes in bipolar disorder

“…[13][14][15][16][17] Progressive neurostructural changes in bipolar disorder therefore might constitute both a cause and consequence of increasing disease burden, creating a feedback loop with significant clinical consequences. 11,19,20 Cross-sectional, correlational studies are hampered by problems retrospectively enumerating mood episodes over a prolonged period of time. However, there are relatively few data confirming the implied association between affective episode number, or other measures of disease burden and either functional activation or related neurochemical changes in the relevant brain regions.…”

“…[3][4][5][6][7][8][9][10] Lower concentrations of N-acetylaspartate (NAA) in the prefrontal cortex of bipolar patients have also been interpreted to partially reflect neuronal loss, consistent with a pattern of atrophic changes. 11,12 Recent models of bipolar disorder build on these findings, hypothesizing that prefrontal neuropathic changes exacerbate an underlying dysregulation of extended limbic networks central to the control and expression of affect.…”

“…Longitudinal functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies have been small, and are often confounded by between-scan differences in mood state. 11,19,20 Cross-sectional, correlational studies are hampered by problems retrospectively enumerating mood episodes over a prolonged period of time.…”