Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder

Abstract

Using novel MRI techniques, we have found abnormalities in cerebral regions related to cortical-limbic pathways in MDD patients.

Increased myo-inositol in the posterior cingulate cortex in first-episode major depressive patients

“…The findings of altered metabolite levels in the PCC in this study support the notion that the PCC may be involved in pathological rumination and self-focused attention in depression; however, metabolite levels in the PCC of depressed patients have not yet been assessed; thus the increase in the resonance peak of mI in the PCC cannot be directly compared with other studies. Nevertheless, the present results of increased mI levels in the PCC in MDDG are in line with studies showing morphological alterations [21,23], lower electroencephalographic activation at rest [24], and higher metabolic activation during rumination [20] in MDD patients. The literature contains reports of functional hyper-connectivity in the PCC and the subgenual-cingulate cortex, correlated with behavioral measures of rumination and brooding in relation to the severity of depression [24]; and of the PCC with the dorsomedial prefrontal cortex, correlated with depressive symptoms in MDD [14].…”

“…Our MDD patients did not differ from healthy controls in the other metabolites measured. The lack of any such significant differences agrees with studies of anterior brain regions and with similar conditions as our patients in the MDDG that found no differences in other brain metabolites like Glu, Cr [31][32][33][34]37], NAA [31,33,34] or Cho [21,31,33]; however, the possibility that these variations are due to the small number of participants cannot be discarded. In conclusion, to the best of our knowledge this is the first evidence of metabolite alterations in the PCC in moderate-to-severe depression in first-episode, medication-naïve patients.…”

“…The PCC has been found to be activated in healthy subjects during information retrieval from episodic [16] and autobiographic memories [17], as well as during self-referential processing [10,18,19], and rumination [20]. Interestingly, some neuroimaging studies have found both structural and activity alterations in the PCC of MDD patients; for example, MDD patients have reduced cortical thickness [21], decreased gray matter volume [22] and lesser cortical folding and gyrification index over PCC [23]. MDD patients show electroencephalographic hypoactivation over the posterior cingulate while at rest [24], and decreased blood flow with sad, compared to neutral word retrieval [25]; whereas they present greater activation in the PCC than controls during rumination compared to the abstract distraction condition [20], and to sad faces compared to healthy volunteers before antidepressant treatment.…”

“…It participates in signaling processes in the phosphatidylcholine system and is involved in the regulation of cellular osmolarity; therefore, it has been considered as a possible marker of inflammatory responses in the brain and of glial cell loss [27,29]. Levels of mI have been found to be lower in the anterior cingulate cortex [21], as has the mI/Cr (creatine) ratio in the left and right prefrontal regions [30] and in the prefrontal and anterior cingulate cortices in medicated patients after several weeks of wash-out [31]. In contrast, higher levels have been seen in the medial prefrontal cortex and pregenual cingulate cortex of medication-free, fully-recovered patients [32] and in the left dorsolateral prefrontal cortex in treatment-naïve, first-episode, female patients and after antidepressant treatment [33].…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…Specifically, remitters showed increased while non-remitters showed decreased cortical thickness in several regions, indicating that structural recovery might occur only if patients respond to treatment. Interestingly, among the entire sample who received pharmacotherapy, only remitters showed increased hippocampal volume and cortical thickness in the rostral middle frontal gyrus, orbitofrontal cortex, and inferior temporal gyrus, whereas a previous study documented increased orbitofrontal cortical thickness in both remitters and non-remitters after antidepressant treatment [33]. Thus, it has been suggested that the reversible alterations in some frontal regions might be associated with remission itself or with antidepressant effects.…”