Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis

Abstract

Background. Because cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.Method. A systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.Results. A total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.Conclusions. By excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal-limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.

Abnormal cerebellar volume in acute and remitted major depression

“…Several meta-analyses considering automated and userindependent structural data analysis approaches, such as voxel-based morphometry (VBM), have consistently demonstrated gray matter volume (GMV) reductions in anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and hippocampus in patients with MDD (Bora et al 2012, Du et al 2012, Lai 2013, Zhao et al 2014). These investigations have reinforced existing neuroanatomical models of affective disorder (Price and Drevets 2012).…”

“…While only few studies have explicitly addressed the effects of antidepressant treatment on GMV (Hamilton et al 2008, Smith et al 2013, Kong et al 2014, Zhao et al 2014, preliminary evidence suggests that selective serotonin reuptake inhibitor treatment may be associated with GMV increase in DLPFC (Smith et al 2013), ACC (Zhao et al 2014, Willard et al 2015 and/or amygdala (Hamilton et al 2008). In an attempt to distinguish morphological features of the disease itself from those of treatment, were here included subgroups of medicated and non-medicated patients with acute MDD, as well as a subgroup of remitted patients on maintenance therapy.…”

“…Yet to the best of our knowledge, this is the first report investigating cerebellar abnormalities in MDD using a specific data analysis protocol for infratentorial structures and a patient sample characterized by acute symptom load, symptom remission, and presence/absence of drug treatment. Thus, replication is warranted by future studies, as much as investigations are needed to establish potential gender-specific effects A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT on brain structure in MDD (Zhao et al 2014).…”

Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats

“…Depression is associated with atrophy and loss of neurons in limbic and cortical brain areas, which could contribute to the symptoms of depression [23]. Moreover, magnetic resonance imaging shows smaller hippocampal volume in depressed patients besides changes in other limbic areas [36,37]. We have proposed that chronic hyperglycemia, imposed by the diabetic condition, is a more reliable animal model to mimic human depression since, unlike from acute stressors, it affects brain plasticity and function over time [2,9,32].…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…Thus, structural alterations in the ACC may be associated with the affective and cognitive dysfunctions in MDD. Some studies have focused on the early morphological changes in first-episode, medication-naive MDD patients [28][29][30]. A recent study in untreated, firstepisode, mid-life MDD patients showed a modestly negative correlation between cortical thickness in the rostral middle frontal cortex and depression severity based on the Hamilton Depression Rating Scale (HDRS) [31] (Fig.…”