Neurochemical and microstructural alterations in bipolar and depressive disorders: A multimodal magnetic resonance imaging study

Abstract

AimsDepression in bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatments and poor clinical outcomes in many bipolar patients. Herein, we report direct comparisons between medication-free patients with BD and those with UD in terms of the microstructure and neurometabolites in eight brain regions.MethodsA total of 20 patients with BD, 30 with UD patients, and 20 matched healthy controls (HCs) underwent 3.0T magnetic resonance imaging with chemical exchange saturation transfer (CEST) for glutamate (Glu; GluCEST) imaging, multivoxel magnetic resonance spectroscopy, and diffusion kurtosis imaging.ResultsCompared with HCs, patients with UD showed significantly lower levels of multiple metabolites, GluCEST% values, and diffusional kurtosis [mean kurtosis (MK)] values in most brain regions. In contrast, patients with BD presented significantly higher levels of Glu in their bilateral ventral prefrontal white matter (VPFWM), higher choline (Cho)-containing compounds in their left VPFWM and anterior cingulate cortex (ACC), and higher GluCEST% values in their bilateral VPFWM and ACC; moreover, reduced MK in these patients was more prominent in the left VPFWM and left thalamus.ConclusionThe findings demonstrated that both patients with UD and BD have abnormal microstructure and metabolic alterations, and the changes are not completely consistent in the prefrontal lobe region. Elevated Glu, Cho, and GluCEST% in the ACC and VPFWM of patients with UD and BD may help in differentiating between these two disorders. Our findings support the significance for the microstructural integrity and brain metabolic changes of the prefrontal lobe region in BD and UD.

Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome

“…For instance, NAA levels increased after a pharmacological treatment of HIV [158]. Similarly, lower NAA levels have been observed reliably in people diagnosed with depression [70,81,82], which were normalized by SSRI treatment [159,160]. In the present study, the NAA levels were inversely associated with the PASC group scores on a brief test of recent verbal memory [103], which is broadly consistent with reports of moderate correlations with cognitive ability [161].…”

“…Based on its sensitivity to neuronal dysfunction, NAA has been used as a marker of neuronal integrity, viability, density, and metabolic homeostasis [78,79]. Indeed, reduced NAA has been reliably reported for traumatic brain injury [80], depression [70,81,82], neuroinflammation [83], and a range of brain-based disorders [84].…”

A Magnetic Resonance Spectroscopy Study on Polarity Subphenotypes in Bipolar Disorder

“…Of note, in a recent study on ACC, decreased Cr and tCr were found in euthymic BD compared to healthy individuals, while increased PCr and lower Cr/PCr ratio in ACC were associated with greater severity of physical and sexual abuse in the BD group only [ 90 ]. With regard to the PCC, an area with increased tCr in our study in both manic and depressive polarities, few studies are available in BD while data on the metabolite profile of PCC are limited [ 91 , 92 , 93 ]. Previous studies focusing on PCC in BD and unipolar depression groups [ 92 , 93 ] or acutely manic BD and acutely ill patients with schizophrenia [ 89 ] did not find Cr changes in BD.…”

“…Given that Cho is considered a marker of phospholipid membrane metabolism, the observed elevated levels in our study probably indicate increased membrane breakdown in PCC and hippocampus in manic and to a lesser degree depressive polarities compared to healthy individuals. In a recent study on BD and unipolar depression, Kong and colleagues reported increased Cho in PCC in the BD group but not in unipolar depression compared to healthy individuals [ 91 ].…”

The Cerebellum’s Role in Affective Disorders: The Onset of Its Social Dimension

“…Regarding this, there are studies assuming that 5-HT3R antagonists provide anti-depressant effects [10,14]. Although the "monoamine hypothesis" is the most accepted theory, recent works have shown an increasing role played by GABA and Glu in the progression of MDD [4,7,10,18] and BD [19]. GABAergic projections are from the hypothalamus (Hyp) to the occipital and parietal cortex, from Hip to PFC and NA and from the thalamus (Thl) to the Ventral Tegmental Area (VTA) [7,10].…”