Reduced amygdala–prefrontal coupling in major depression: association with MAOA genotype and illness severity
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The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects. In our control group, we observed tight coupling of the amygdala and dorsal prefrontal areas comprising the dorsolateral prefrontal cortex (DLPFC), dorsal parts of the anterior cingulate cortex (dACC), and lateral orbitofrontal cortex. Amygdala-prefrontal connectivity was significantly reduced in depressed patients and carriers of the higher active MAOA risk alleles (MAOA-H). Hence, depressed MAOA-H carriers showed the weakest amygdala-prefrontal coupling of the investigated subgroups. Furthermore, reduced coupling of this circuitry predicted more than 40% variance of clinical variables characterizing a longer and more severe course of disease. We conclude that genetic variation in the MAOA gene may affect the course of major depression by disrupting cortico-limbic connectivity.
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MDD is linked to reduced cortico-limbic functional connectivity (e.g., mPFC↔amygdala) when presented with negative cues.
“MDD has been linked to reduced cortico-limbic functional connectivity (e.g., mPFC↔amygdala) when presented with negative cues [175-178].”
From Prefrontal cortex and depression (2022) · cites this paper as [175]
The Discussion reports reduced amygdala–DLPFC and amygdala–dACC connectivity in depressed patients during emotion processing. However, the fMRI methods include sad, angry, happy, and neutral faces, and the connectivity analysis does not isolate responses to negative cues. The reported regions are DLPFC and dACC rather than a specifically identified mPFC–amygdala connection. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThese patterns (amygdalar hyperactivity and reduced cortico-limbic functional connectivity) were linked to greater depression severity and a longer disease duration.
“these patterns were linked to greater depression severity and a longer disease [175, 176, 178]”
From Prefrontal cortex and depression (2022) · cites this paper as [175]
The Association with illness severity section (page unavailable) reports that reduced amygdala–DLPFC connectivity correlated with an illness-severity index that included duration of illness. The cited passages do not establish that amygdalar hyperactivity was linked to severity or duration; the reported amygdala activation was a task effect across the whole sample. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe same group found that amygdala-DLPFC connectivity was significantly associated with illness severity, with reduced connectivity linked to a more severe and pervasive course.
“However, the same study group found that amygdala-DLPFC connectivity was significantly associated with illness severity, indicating that patients with MDD with reduced connectivity between these regions had a more pervasive and severe course of illness.58”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [58]
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Monoamine oxidase A gene DNA hypomethylation - A risk factor for panic disorder?
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- Authors
- Dannlowski, U., Ohrmann, P., Konrad, C., Domschke, K., Bauer, J., Kugel, H., Hohoff, C., Schöning, S., Kersting, A., Baune, B. T., Mortensen, L. S., Arolt, V., Zwitserlood, P., Deckert, J., Heindel, W., & Suslow, T.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Suslow, Thomas
- ORCID
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-11
- Volume
- 12
- Issue
- 01
- Pages
- 11
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2101006267
- Cited by
- 216
- References
- 67
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 14 · 2020: 10 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 16 · 2015: 18 · 2014: 24 · 2013: 9 · 2012: 21
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- major depressive disorder, amygdala, prefrontal cortex, functional connectivity, monoamine oxidase A, facial expression processing, emotion regulation, disease severity, clinical course, anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex
- MeSH terms
- Adult, Alleles, Amygdala, Antidepressive Agents, Chronic Disease, Major Depressive Disorder, Emotions, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Monoamine Oxidase, Neural Pathways, Neuropsychological Tests, Psychiatric Status Rating Scales, Cluster Analysis, Treatment Outcome, Prefrontal Cortex
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