Grey matter volume abnormalities in the first depressive episode of medication-naïve adult individuals: a systematic review of voxel based morphometric studies

Abstract

Background

To identify the reliable and consistent grey matter volume (GMV) abnormalities associated with major depressive disorder (MDD), we excluded the influence of confounding clinical characteristics, comorbidities and brain degeneration on brain morphological abnormalities by inclusion of non-comorbid and non-geriatric drug-naïve MDD individuals experiencing first episode depressive.

Methods

The PubMed, Scopus, Web of Science, Science Direct and Google scholar databases were searched for papers published in English up to April 2020.

Results

A total of 21 voxel based morphometric (VBM) studies comparing 845 individuals in the first depressive episode and medication-naïve with 940 healthy control subjects were included. The results showed a grey matter volumes reductions in the orbitofrontal cortex (OFC), prefrontal cortex (PFC), frontal and temporal gyri, temporal pole, insular lobe, thalamus, basal ganglia, cerebellum, hippocampus, cingulate cortex, and amygdala. In addition, increased grey matter volumes in the postcentral gyrus, superior frontal gyrus, insula, basal ganglia, thalamus, amygdala, cuneus, and precuneus differentiated the first depressive episode in medication-naïve individuals from healthy subjects.

Conclusion

The present systematic review provided additional support for the involvement of grey matter structural abnormalities in limbic-cortical circuits as possibly specific structural abnormalities in the early stage of MDD.

Key points

• Distinct brain regions in MDD patients might be associated with the early stages of illness, and thus it is critical to study the causal relationship between brain structures and the onset of the disease to improve the evaluation in clinic.

• Grey matter alterations in the fronto-limbic networks in the first episode, medication-naïve MDD might suggest that these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.

• First episode, medically naïve depressive patients show grey matter volume alterations in brain regions mainly associated with emotion regulation including parietal–temporal regions, PFC, insular lobe, thalamus, basal ganglia, cerebellum and limbic structures that may be specific changes in early stage of MDD.

• Genotype–diagnosis interaction effects on brain morphology in the cortico-limbic-striatal circuits, including the PFC, amygdala, hippocampus and striatum that might be implicated in the dysfunctional regulation of emotion in first-episode MDD patients.

• Future longitudinal and prospective studies should be conducted to identify the core structural brain changes in people at-risk for MDD and explore the association of their brain volumes with symptom onset.

Keywords:

• Major depressive disorder
• first episode
• medication naïve
• grey matter volume
• voxel-based morphometry

Disclosure statement

No potential conflict of interest was reported by the authors and there is no financial support for this publication that can influence the outcome.

Additional information

Funding

Translational Psychiatry Program (USA) is funded by a grant from the National Institute of Health/National Institute of Mental Health (1R21MH117636-01A1, to JQ). Center of Excellence on Mood Disorders (USA) is funded by the Pat Rutherford Jr. Chair in Psychiatry, John S. Dunn Foundation and Anne and Don Fizer Foundation Endowment for Depression Research. Translational Psychiatry Laboratory (Brazil) is funded by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (GZR and JQ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (JQ), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) (GZR and JQ), and Instituto Cérebro e Mente (JQ and GZR). JQ is a 1A CNPq Research Fellow.