Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis

Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis

J Psychiatry Neurosci 2020;45(6):406-429 | PDF | Appendix

Daniela A. Espinoza Oyarce, MNeurosci; Marnie E. Shaw, PhD; Khawlah Alateeq, MMagResonTech; Nicolas Cherbuin, PhD

Background: Structural differences associated with depression have not been confirmed in brain regions apart from the hippocampus. Comorbid anxiety has been inconsistently assessed, and may explain discrepancies in previous findings. We investigated the link between depression, comorbid anxiety and brain structure.

Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42018089286). We searched the Cochrane Library, MEDLINE, PsycInfo, PubMed and Scopus, from database inception to Sept. 13, 2018, for MRI case–control studies that reported brain volumes in healthy adults and adults with clinical depression. We summarized mean volumetric differences using meta-analyses, and we assessed demographics, depression factors and segmentation procedure as moderators using meta-regressions.

Results: We included 112 studies in the meta-analyses, assessing 4911 healthy participants and 5934 participants with depression (mean age 49.8 yr, 68.2% female). Volume effects were greater in late-onset depression and in multiple episodes of depression. Adults with depression and no comorbidity showed significantly lower volumes in the putamen, pallidum and thalamus, as well as significantly lower grey matter volume and intracranial volume; the largest effects were in the hippocampus (6.8%, p < 0.001). Adults with depression and comorbid anxiety showed significantly higher volumes in the amygdala (3.6%, p < 0.001). Comorbid anxiety lowered depression effects by 3% on average. Sex moderated reductions in intracranial volume.

Limitations: High heterogeneity in hippocampus effects could not be accounted for by any moderator. Data on symptom severity and medication were sparse, but other factors likely made significant contributions.

Conclusion: Depression-related differences in brain structure were modulated by comorbid anxiety, chronicity of symptoms and onset of illness. Early diagnosis of anxiety symptomatology will prove crucial to ensuring effective, tailored treatments for improving long-term mental health and mitigating cognitive problems, given the effects in the hippocampus.


Submitted Sep. 17, 2019; Revised Feb. 7, 2020; Accepted Feb. 27, 2020; Published online July 29, 2020

Affiliations: From the Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, ACT, Australia (Espinoza Oyarce, Alateeq, Cherbuin); and the College of Engineering and Computer Science, The Australian National University, Canberra, ACT, Australia (Shaw).

Funding: D. Espinoza Oyarce is funded by the Australian Government Research Training Program (AGRTP) Scholarship. The funder had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the review; and in the decision to submit the paper for publication.

Competing interests: None declared.

Contributors: D. Espinoza Oyarce and N. Cherbuin designed the study. All authors acquired and analyzed the data. D. Espinoza Oyarce, M. Shaw and N. Cherbuin wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

ORCID: Daniela A. Espinoza Oyarce (https://orcid.org/0000-0002-0843-9195). Marnie E. Shaw https://orcid.org/0000-0002-9834-6725). Nicolas Cherbuin (https://orcid.org/0000-0001-6481-0748).

DOI: 10.1503/jpn.190156

Correspondence to: D.A. Espinoza Oyarce, Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Florey Building 54, Mills Road, Acton 2601, Canberra, Australia; danielaandrea.espinozaoyarce@anu.edu.au