Location of altered brain metabolite levels found in bipolar I patients

Bipolar I disorder patients have increased phospholipid levels in the thalami and increased N-acetyl-aspartate (NAA) levels in the left hippocampus compared with healthy individuals, a team of investigators has discovered.

"While MRS [magnetic resonance spectroscopy] data on bipolar data remain somewhat inconsistent, the findings here are consistent with other evidence supporting the hypothesis that dysfunctional thalamocortical gating plays a role in bipolar disorder," report Fleur Howells and colleagues from the University of Cape Town in South Africa.

They add: "Further enquiry into the functioning of the glial cells in the thalami of individuals with bipolar I disorder, should be pursued in future studies of bipolar I disorder."

The researchers studied 19 individuals with euthymic bipolar I disorder and eight mentally healthy controls, administering the Young Mania Rating Scale and Hospital Depression and Anxiety Scale. All participants underwent proton magnetic resonance imaging (¹H-MRS) with two-dimensional chemical shift imaging to determine brain concentration profiles of NAA, choline metabolites, and myo-inositol in the hippocampal complexes, the brain stem, including the locus Creoles, and the dorsal thalami.

Bipolar I disorder patients had a range of comborbidities, including anxiety disorders, impulse control disorders, eating disorders, substance-related disorders, personality disorders, and a dissociative disorder. All patients were receiving mood stabilizing drugs, and three had undergone electroconvulsive shock therapy (ECT). Patients reported an average of 2.8 manic episodes and 3.4 depressive episodes, with one reporting have undergone three mixed episodes.

The team reports in Progress in Neuro-Psychopharmacology and Biological Psychiatry that bipolar I disorder patients had significantly increased choline metabolite concentrations in the thalami compared with controls, and significantly increased relative NAA concentrations in the left hippocampus. There were no other significant differences in metabolite concentrations.

The finding of alterations in thalami indicate possible reduced thalamocortial connectivity, which the researchers say may contribute to "dysregulation of behavioural systems required for attentional processes."

Also, increased relative NAA concentrations suggest that there is an increase in myelin production and mitochondrial function, which is consistent with the finding of increased phospholipid concentration in the thalami and may be indicative of neuro-inflammation, they add.

The researchers note that on ANCOVA analysis, the relative differences in metabolite concentrations were unaffected by age, symptom severity, type of medication taken, or ECT.

Liam Davenport, medwireNews Reporter

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