Medial prefrontal aberrations in major depressive disorder revealed by cytoarchitectonically informed voxel-based morphometry
Open accessAbstract
OBJECTIVE: The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The authors performed morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and comparison subjects using both uni- and multivariate statistics. METHOD: Multisite voxel- and region-based morphometric MRI analysis was conducted in 73 depressed patients and 73 matched comparison subjects without psychiatric history. Frontal pole volume was first compared between depressed patients and comparison subjects by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. RESULTS: Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients, with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients. CONCLUSIONS: Across disparate methods, subregion specificity in the left medial frontal pole volume in depressed patients was demonstrated. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology, such as the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression.
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Smaller hippocampal and medial prefrontal cortex volumes are consistently linked to longer duration of major depressive disorder.
“longer illness duration (24,26–30)”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [24]
Smaller hippocampal and medial prefrontal cortex volumes are consistently linked to a more recurrent or relapsing course of major depressive disorder.
“they have been consistently associated with markers of a progressive course of MDD characterized by more recurrent episodes/relapses (3,19–25)”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [24]
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“Several prior studies have implicated dysregulation in themedial portion of BA 10 in patientswithmajor depression (77, 78), and thepolar components ofVMPF10maybe smaller in patients with major depression compared with healthy controls (79).”
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- Authors
- Bludau, S., Bzdok, D., Gruber, O., Kohn, N., Riedl, V., Sorg, C., Palomero-Gallagher, N., Müller, V. I., Hoffstaedter, F., Amunts, K., & Eickhoff, S. B.
- Affiliations
- Forschungszentrum Jülich (DE)
- From the Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany; the Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; the Center for Translational Research in Systems Neuroscience and Psychiatry, Clinic for Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany; the Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of...
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2016-03-01
- Volume
- 173
- Issue
- 3
- Pages
- 291-298
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5441234
- OpenAlex
- W2175558603
- Cited by
- 67
- References
- 43
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 3 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 4 · 2019: 3 · 2018: 8 · 2017: 7 · 2016: 2
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- mediaTUM (Technical University of Munich) (submittedVersion)
- GRO (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- European Commission (604102, 2007–2013, FP7 2007-2013, FP7/2007)
- Deutsche Forschungsgemeinschaft (, EI 816/6-1, LA 3071/3‐1, 816/4-1, 3071/3-1, FP7/2007–2013, EI 816/4–1)
- Servier
- National Institute of Mental Health (R01MH074457, EI 816/6-, MH074457)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- major depressive disorder, brain structural changes, medial prefrontal cortex, disease severity, disease duration, anterior cingulate cortex, amygdala, uncinate fasciculus, searchlight analysis, support vector machine, cytoarchitecture
- MeSH terms
- Adult, Major Depressive Disorder, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Psychiatric Status Rating Scales, Case-Control Studies
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