Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A ¹H magnetic resonance spectroscopy study

Abstract

Aim:We utilized single-voxel 1 H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Methods:Fifteen adult MDD patients and 15 ageand sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment.Results: At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Conclusion:Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas.

Evaluation of Myo-Inositol as a Potential Biomarker for Depression in Schizophrenia

“…In neuro-inflammatory conditions, elevated myo-Inositol levels are presumed to reflect astrocyte and microglial activation (Chang et al, 2014, Kirov et al, 2013; conversely, reduced myo-Inositol levels have been interpreted as evidence of astrocyte necrosis in neuromyelitis optica (Ciccarelli et al, 2013). Several postmortem studies have found reduced density of glial cells (Ongür et al, 1998;Hamidi et al, 2004) and decreased concentration of protein markers specific to astrocytes in MDD (MiguelHidalgo et al, 2000;Miguel-Hidalgo et al, 2011;MiguelHidalgo et al, 2014), providing a histological basis for interpreting reduced myo-Inositol levels in MDD as evidence of glial dysfunction (Coupland et al, 2005;Chen et al, 2014). Analysis of post-mortem tissue has also implicated reduction in glial numbers in schizophrenia (Rajkowska et al, 2002;Stark et al, 2004), though MRS studies, including this current study, have generally found no evidence of altered levels of myo-Inositol in schizophrenia Schwerk et al, 2014).…”

“…Consistently, proton magnetic resonance imaging ( 1 H-MRS) studies of patients with major depressive disorder (MDD) report reduced levels of myo-Insoitol in prefrontal and anterior cingulate cortex (ACC; Frey et al, 1998;Coupland et al, 2005;Chen et al, 2014). Conversely, positive clinical outcome in MDD is associated with increased myo-Inositol levels (Chen et al, 2014;Zheng et al, 2010). These data indicate that reduced myo-Inositol in MDD is primarily associated with depression symptoms rather than being secondary to treatment.…”

“…Myo-Inositol contributes to glial osmoregulatory functioning (Strange, 1992;Fisher et al, 2002), as well as a wide range of other structural and signaling functions. Consistently, proton magnetic resonance imaging ( 1 H-MRS) studies of patients with major depressive disorder (MDD) report reduced levels of myo-Insoitol in prefrontal and anterior cingulate cortex (ACC; Frey et al, 1998;Coupland et al, 2005;Chen et al, 2014). Conversely, positive clinical outcome in MDD is associated with increased myo-Inositol levels (Chen et al, 2014;Zheng et al, 2010).…”

Frontal Cortex Myo-Inositol Is Associated with Sleep and Depression in Adolescents: A Proton Magnetic Resonance Spectroscopy Study

“…On the contrary, bipolar disorder may be characterized by elevated frontal cortex mI concentrations, and the anti-manic effects of lithium may be associated with a reduction of mI [61]. Electro-convulsive treatment (ECT) may increase mI concentrations [60]. These results are not, however, unanimous, as some studies have reported increased or similar mI levels in depressed patients versus healthy controls [24,62,63].…”

“…It has been suggested that a reduced cerebral mI concentration is a neurochemical biomarker for depression; lower inositol has been reported in the cerebrospinal fluid of depressed patients [56] as well as in the frontal cortex of suicide victims (postmortem) and patients with bipolar disorder [57]. Some 1 H MRS studies have observed lower cerebral mI concentrations in depressed patients than in controls [48,58,59,60]. On the contrary, bipolar disorder may be characterized by elevated frontal cortex mI concentrations, and the anti-manic effects of lithium may be associated with a reduction of mI [61].…”