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Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation.

ABSTRACT: The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy (¹H-MRS) at 3?T, utilizing a 2-dimensional J-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluid-corrected ACC metabolite concentrations were compared between healthy control (HC, n?=?16), depressed without SI (Dep/SI-, n?=?13), and depressed with SI (Dep/SI+, n?=?11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and the N-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI-?and Dep/SI+?adolescents. Dep/SI+?adolescents had higher Glx than Dep/SI-?participants (p_adj?=?0.012) and had lower NAA/Glx than both Dep/SI-?(p_adj?=?0.002) and HC adolescents (p_adj?=?0.039). There were significant relationships between SI intensity and Glx (p_FDR?=?0.026), SI severity and NAA/Glx (p_FDR?=?0.012), and SI intensity and NAA/Glx (p_FDR?=?0.004). ACC Glx and NAA/Glx discriminated Dep/SI-?from Dep/SI+?participants. Uncoupled NAA-glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior.

SUBMITTER: Lewis CP

PROVIDER: S-EPMC7181616 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation.

Lewis Charles P CP Port John D JD Blacker Caren J CJ Sonmez A Irem AI Seewoo Bhedita J BJ Leffler Jarrod M JM Frye Mark A MA Croarkin Paul E PE

Translational psychiatry 20200423 1

The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) at 3 T, utilizing a 2-dimensional J-averaged PRESS ...[more]

PMID: 32327639

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Project description:Physiological and psychological underpinnings of suicidal behavior remain ill-defined and lessen timely diagnostic identification of this subgroup of patients. Arterial stiffness is associated with autonomic dysregulation and may be linked to major depressive disorder (MDD). The aim of this study was to investigate the association between arterial stiffness by photo-plethysmogram (PPG) in MDD with and without suicidal ideation (SI) by applying multiscale tone entropy (T-E) variability analysis. Sixty-one 10-min PPG recordings were analyzed from 29 control, 16 MDD patients with (MDDSI+) and 16 patients without SI (MDDSI-). MDD was based on a psychiatric evaluation and the Mini-International Neuropsychiatric Interview (MINI). Severity of depression was assessed using the Hamilton Depression Rating Scale (HAM-D). PPG features included peak (systole), trough (diastole), pulse wave amplitude (PWA), pulse transit time (PTT) and pulse wave velocity (PWV). Tone (Diastole) at all lags and Tone (PWA) at lags 8, 9, and 10 were found to be significantly different between the MDDSI+ and MDDSI- group. However, Tone (PWA) at all lags and Tone (PTT) at scales 3-10 were also significantly different between the MDDSI+ and CONT group. In contrast, Entropy (Systole), Entropy (Diastole) and Tone (Diastole) were significantly different between MDDSI- and CONT groups. The suicidal score was also positively correlated (r = 0.39 ~ 0.47; p < 0.05) with systolic and diastolic entropy values at lags 2-10. Multivariate logistic regression analysis and leave-one-out cross-validation were performed to study the effectiveness of multi-lag T-E features in predicting SI risk. The accuracy of predicting SI was 93.33% in classifying MDDSI+ and MDDSI- with diastolic T-E and lag between 2 and 10. After including anthropometric variables (Age, body mass index, and Waist Circumference), that accuracy increased to 96.67% for MDDSI+/- classification. Our findings suggest that tone-entropy based PPG variability can be used as an additional accurate diagnostic tool for patients with depression to identify SI.

Project description:ContextAnhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of γ-aminobutyric acid (GABA).ObjectiveTo test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored.DesignCase-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T.SettingTwo clinical research divisions at 2 teaching hospitals.ParticipantsTwenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12-19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age.Main outcome measuresAnterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable.ResultsCompared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t = 3.2; P < .003). When subjects with MDD were categorized based on the presence of anhedonia, only anhedonic patients had decreased GABA/w levels compared with control subjects (t = 4.08; P < .001; P(Tukey) < .001). Anterior cingulate cortex GABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r = -0.50; P = .02), as well as for the entire participant sample including the control subjects (r = -0.54; P < .001). Anterior cingulate cortex white matter was also significantly decreased in adolescents with MDD compared with controls (P = .04).ConclusionsThese findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in the present study, may permit greater specificity in evaluating this important clinical feature.

Dataset Information

Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation.

Publications

Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation.

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