A <sup>1</sup>HMRS study of the anterior cingulate gyrus in euthymic bipolar patients

Amaral, José Antônio; Tamada, Renata Sayuri; Issler, Cilly Klüger; Caetano, Sheila C.; Cerri, Giovanni Guido; Castro, Cláudio Campi de; Lafer, Beny

doi:10.1002/hup.761

Cited by 21 publications

(3 citation statements)

References 38 publications

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“…Although the mechanistic contributions have yet to be definitively elucidated, changes to the 1 H-MRS choline resonance are believed to reflect non-steady state alterations to the rate of membrane synthesis and breakdown, and/or changes in cell density (Rae, 2014). In addition to the findings reported here in adolescents, studies in adults with BD have found no difference in choline between BD and healthy controls (Amaral et al, 2006; Kraguljac et al, 2012; Scherk et al, 2009). However, because the tCho concentration is known to display regional differences in normal brain of up to 46% (Bracken et al, 2011), is thought to vary with mood state (Charles et al, 1994), and can potentially be affected by drugs lithium and valproic acid (Moore et al, 2000; Silverstone et al, 2004), our findings must be considered limited in their applicability to the ACC, in depressed patients not currently taking mood stabilizing medications.…”

Section: Discussionsupporting

confidence: 63%

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

Xian¹,

Forrest²,

Kuykendall³

et al. 2014

Journal of Affective Disorders

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Background Delayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology. Case-control studies utilizing proton-1 magnetic resonance spectroscopy (1H-MRS) have found increased total choline levels in several brain regions in MDD. However, there are no published 1H-MRS reports directly comparing adolescents with MDD and BD. We hypothesized that ACC choline levels would be increased in adolescents with unipolar versus bipolar depression. Methods We studied depressed adolescents with MDD (n=28; mean age 17.0±2.1 years) and BD (n=9; 17.3±3.1 years). A Siemens Verio 3-Tesla clinical MRI system was used to acquire scans, using a single-voxel PRESS sequence. The voxel (18.75 cm3) was positioned on the ACC in the midsagittal plane. To remove potential gender effects, only female adolescent participants were included. Data were analyzed using the ANOVA and post-hoc Tukey tests. Results A significantly increased ACC choline/creatine ratio was observed in participants with MDD (mean=0.253±0.021) compared to BD (mean=0.219±0.020) (p=0.0002). There were no significant differences in the other 1H-MRS metabolites. Limitations Cross sectional design, single gender sample, limited sample size. Conclusions The present findings suggest that ACC total choline may have the potential to serve as a diagnostic biomarker in adolescent mood disorders.

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Section: Discussionsupporting

confidence: 63%

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

Xian¹,

Forrest²,

Kuykendall³

et al. 2014

Journal of Affective Disorders

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“…The findings from the present study are in agreement with some papers that did not find differences in brain metabolite levels in the prefrontal cortex of bipolar patients compared to healthy controls [ 15 , 26 ]. Also, these results could be explained by the use of the same methodology, such as only evaluating BD I patients under strict criteria of euthymia; assessed patients had been receiving lithium alone for a long time or associated with another psychiatric drug, including other mood stabilizers, antipsychotics, and antidepressants.…”

Section: Discussionsupporting

confidence: 94%

Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

et al. 2015

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Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD), but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS). The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

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“…While some cross-sectional studies involving euthymic BD patients mostly on lithium treatment have reported similar NAA levels and similar or lower NAA/tCr ratio compared with healthy controls in anterior cingular cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and frontal cortex (FC) (Amaral et al, 2006; Brambilla et al, 2005; Hamakawa et al, 1999; Molina et al, 2007), higher NAA/tCr ratio in lithium-treated BD patients has also been found in DLPFC (Brambilla et al, 2005). Euthymic BD patients who were medication free for at least 2 weeks have been found to have lower DLPFC NAA/tCr ratio (Winsberg et al, 2000), whereas manic/mixed patients have been reported to have decreased NAA levels in medial orbital prefrontal cortex and similar NAA levels in DLPFC compared with healthy controls (Cecil et al, 2002; Michael et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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

Aydın

Yurt

Gökmen

et al. 2016

Journal of Affective Disorders

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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.

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A ¹HMRS study of the anterior cingulate gyrus in euthymic bipolar patients

Abstract: We did not find a significant difference in the NAA/Cr and Cho/Cr ratio between bipolar patients and healthy controls. Chronic administration of psychotropic drugs could have had an effect on NAA/Cr levels of bipolar patients.

Cited by 21 publications

References 38 publications

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

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

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A 1HMRS study of the anterior cingulate gyrus in euthymic bipolar patients

Abstract: We did not find a significant difference in the NAA/Cr and Cho/Cr ratio between bipolar patients and healthy controls. Chronic administration of psychotropic drugs could have had an effect on NAA/Cr levels of bipolar patients.

Cited by 21 publications

References 38 publications

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: A potential new tool for diagnosis

Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

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

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A ¹HMRS study of the anterior cingulate gyrus in euthymic bipolar patients