Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients

Caetano, Sheila C.; Fonseca, Manoela; Olvera, Rene L.; Nicoletti, Mark; Hatch, John P.; Stanley, Jeffrey A.; Hunter, Kristina; Lafer, Beny; Pliszka, Steven R.; Soares, Jair C.

doi:10.1016/j.neulet.2005.04.099

Cited by 69 publications

(69 citation statements)

References 36 publications

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“…The increase of choline and creatine without a concomitant N-acetylaspartate decline, as observed here, suggests accelerated membrane turnover but without neurodegeneration. While preliminary, this finding is concordant with those of other studies of pediatric major depression that found no N-acetylaspartate decline, albeit in different brain regions (42)(43)(44)(45)47). In contrast, Nacetylaspartate loss was reported in the caudate in adults with major depression in a small (N=7) study that analyzed N-acetylaspartate/creatine ratios (15).…”

supporting

confidence: 89%

“…Using similar three-dimensional 1 H-MRS, Farchione et al (42) found increased choline concentrations in the left dorsolateral prefrontal cortex, whereas Caetano et al (43), in a later 8-cm 3 single-voxel study, reported decreased choline concentrations in the left dorsolateral prefrontal cortex. In contrast, Mirza et al (44), using single 3-cm 3 voxels, found no differences in choline concentrations in the anterior cingulate cortex.…”

Section: Cholinementioning

confidence: 94%

“…The few studies that quantified creatine concentration in pediatric major depression focused on other brain regions; they reported decreases in the anterior cingulate cortex in adolescent major depression (44) and no abnormalities in the dorsolateral prefrontal cortex (42,43). In adult major depression, the only study of creatine concentrations in the basal ganglia used low-spatial-resolution (27 cm 3 ) single-voxel MRS and did not identify any abnormality (14).…”

Section: Creatinementioning

confidence: 99%

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Lateralized Caudate Metabolic Abnormalities in Adolescent Major Depressive Disorder: A Proton MR Spectroscopy Study

Gabbay

Hess

Liu

et al. 2007

AJP

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Objective-Proton magnetic resonance spectroscopy ( 1 H-MRS) has been increasingly used to examine striatal neurochemistry in adult major depressive disorder. This study extends the use of this modality to pediatric major depression to test the hypothesis that adolescents with major depression have elevated concentrations of striatal choline and creatine and lower concentrations of N-acetylaspartate.Method-Fourteen adolescents (ages 12-19 years, eight female) who had major depressive disorder for at least 8 weeks and a severity score of 40 or higher on the Children's Depression Rating Scale -Revised and 10 healthy comparison adolescents (six female) group-matched for gender, age, and handedness were enrolled. All underwent three-dimensional 3-T 1 H-MRS at high spatial resolution (0.75-cm 3 voxels). Relative levels of choline, creatine, and N-acetylaspartate in the left and right caudate, putamen, and thalamus were scaled into concentrations using phantom replacement, and levels were compared for the two cohorts.Results-Relative to comparison subjects, adolescents with major depressive disorder had significantly elevated concentrations of choline (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left caudate. No other neurochemical differences were observed between the groups.Conclusions-These findings most likely reflect accelerated membrane turnover and impaired metabolism in the left caudate. The results are consistent with prior imaging reports of focal and lateralized abnormalities in the caudate in adult major depression.Rates of major depressive disorder rise dramatically in adolescence, with an estimated lifetime prevalence of 15% in adolescents by ages 15-18. Major depression is associated with significant morbidity, including deterioration in academic functioning, increased risk of substance use, and attempted and completed suicides (1,2). Furthermore, adolescent major depression is a strong predictor of major depression in adulthood, which carries its own burden of disadvantage (3). These findings highlight the need for specific neurobiological research in adolescent major depression.Converging lines of evidence suggest that the pathophysiology of depression entails impairment of cellular resilience and neuroplasticity in specific cortical, subcortical, and limbic brain regions. The relationship between the basal ganglia and depression has been inferred from the high comorbidity between depression and Parkinson's disease as well as Huntington's NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript disease, both basal ganglia-related disorders. In addition, morphometric studies (but not all) and functional neuroimaging studies have documented smaller caudate, putamen, and thalamus as well as impaired metabolism and blood flow in the striatum and thalamus in depression (4-10).Proton magnetic resonance spectroscopy ( 1 H-MRS) has provided additional evidence for the involvement of the striatum in adult major depression. 1 H-MRS provides metabolic assay of ne...

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supporting

confidence: 89%

Section: Cholinementioning

confidence: 94%

Section: Creatinementioning

confidence: 99%

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Lateralized Caudate Metabolic Abnormalities in Adolescent Major Depressive Disorder: A Proton MR Spectroscopy Study

Gabbay

Hess

Liu

et al. 2007

AJP

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“…Abnormal DLPFC function in MDD patients during working memory has been reported. 25,28 Neurochemical 45,46 and neuropathological 6 abnormalities of the DLPFC have also been noted. The theory of prefrontal cortex hypoactivation, that is, 'hypofrontality', in patients with mood disorders has been supported by various studies.…”

Section: Working Memory In Depression K Matsuo Et Almentioning

confidence: 95%

Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder

et al. 2006

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The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age7s.d. = 34.3711.5 years) and 15 healthy comparison subjects (37.7712.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P < 0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P < 0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.

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“…Human MRS studies have identified increased inositol in medial temporal lobe including amygdala (Venkatraman et al, 2009) and in fronto-cortical (PFC, ACC) gray and white matter (Caetano et al, 2005;Kumar et al, 2002) in depression, and in amygdala and thalamus in association with high depression symptoms in fibromyalgia (Valdes et al, 2010); decreased PFC-ACC inositol has also been reported in depression (Coupland et al, 2005). Inositol is an intracellular lipid and precursor of phosphatidylinositol (PI) structural lipids and inositol phosphate secondary messengers e.g.…”

Section: Metabolic and Structural Changes In Cps Micementioning

confidence: 99%

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

et al. 2016

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Human depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward. Using multimodal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we investigated CPS effects on function and structure in the mouse brain under light anesthesia. Mice underwent a baseline MRI/MRS session, followed by 15-day CPS (n=26) or control handling (n=27), and a post-treatment MRI/MRS session. In BOLD fMRI, relative to controls, CPS mice exhibited robust, reproducible increases in FC within 8 of 9 identified cortical networks, including the prefrontal and cingulate cortices that contribute to the "mouse DMN". CPS mice exhibited increases in between-network FC, including amygdala -prefrontal cortex and amygdala -cingulate cortex. MRS identified metabolic alterations in CPS mice as increased inositol levels in amygdala and increased glycerophosphorylcholine levels in prefrontal cortex. Diffusion-weighted MRI detected increased fractional anisotropic values in the cingulum. This study demonstrates that chronic psychosocial stress induces FC states in the mouse brain analogous to those observed in depression, as well as cerebral metabolism and white matter pathway alterations that contribute to understanding of pathological processes. It also demonstrates the importance of brain imaging to the establishment of valid animal models in translational psychiatry. AbstractHuman depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward.Using multimodal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we investigated CPS effects on function and structure in the mouse brain under light anesthesia. Mice underwent a baseline MRI/MRS session, followed by 15-day CPS (n=26) or control handling (n=27), and a posttreatment MRI/MRS session. In BOLD fMRI, relative to controls, CPS mice exhibited robust, reproducible increases in FC within 8 of 9 identified cortical networks, including the prefrontal and cingulate cortices that contribute to the "mouse DMN". CPS mice exhibited increases in b...

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Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients

Cited by 69 publications

References 36 publications

Lateralized Caudate Metabolic Abnormalities in Adolescent Major Depressive Disorder: A Proton MR Spectroscopy Study

Lateralized Caudate Metabolic Abnormalities in Adolescent Major Depressive Disorder: A Proton MR Spectroscopy Study

Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

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