Distinct neurobiological signatures of brain connectivity in depression subtypes during natural viewing of emotionally salient films
Abstract
BACKGROUND: Establishing an evidence-based diagnostic system informed by the biological (dys)function of the nervous system is a major priority in psychiatry. This objective, however, is often challenged by difficulties in identifying homogeneous clinical populations. Melancholia, a biological and endogenous subtype for major depressive disorder, presents a canonical test case in the search of biological nosology. METHOD: We employed a unique combination of naturalistic functional magnetic resonance imaging (fMRI) paradigms - resting state and free viewing of emotionally salient films - to search for neurobiological signatures of depression subtypes. fMRI data were acquired from 57 participants; 17 patients with melancholia, 17 patients with (non-melancholic) major depression and 23 matched healthy controls. RESULTS: Patients with melancholia showed a prominent loss of functional connectivity in hub regions [including ventral medial prefrontal cortex, anterior cingulate cortex (ACC) and superior temporal gyrus] during natural viewing, and in the posterior cingulate cortex while at rest. Of note, the default mode network showed diminished reactivity to external stimuli in melancholia, which correlated with the severity of anhedonia. Intriguingly, the subgenual ACC, a potential target for treating depression with deep brain stimulation (DBS), showed divergent changes between the two depression subtypes, with increased connectivity in the non-melancholic and decreased connectivity in the melancholic subsets. CONCLUSION: These findings reveal neurobiological changes specific to depression subtypes during ecologically valid behavioural conditions, underscoring the critical need to respect differing neurobiological processes underpinning depressive subtypes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A dyshomeostasis-induced sense of low self-efficacy may play a particularly important role in melancholia, a subtype of depression with pronounced somatic symptoms and endocrine disturbances that differs physiologically from other forms of depression with respect to functional connectivity of visceromotor areas, including SGC and ACC.
“Instead, we propose that it may play a particularly important role in melancholia, a subtype of depression with pronounced somatic symptoms and endocrine disturbances (Parker and Paterson, 2014) that differs physiologically from other forms of depression with respect to functional connectivity of visceromotor areas, including SGC and ACC (Guo et al., 2016).”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Guo et al., 2016
Decreased functional connectomes in areas of the DMN and LIM are related to anhedonia.
“On the other hand, the decreased functional connectomes in areas of the DMN and LIM are considered to be related to anhedonia [62-68]”
From Mapping neurophysiological subtypes of major depressive disorder using normative models of the functional connectome (2023) · cites this paper as [62]
Cites
Statistical parametric maps in functional imaging: A general linear approach
Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J. ‐., Frith, C. D., & Frackowiak, R. S. J. (1994) · Human Brain Mapping · doi:10.1002/hbm.460020402 · Cited by 9,688 · see citing works
Dissociable intrinsic connectivity networks for salience processing and executive control
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5587-06.2007 · Cited by 7,426 · see citing works
How do you feel — now? The anterior insula and human awareness
(Bud) Craig, A. D. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2555 · Cited by 6,657 · cited 1× · see citing works
“The anterior insula respond robustly to emotionally salient stimuli, such as pain and disgust, and are thought to serve as a hub that integrates interoand exteroceptive information and generates the subjective experience of emotion (Craig, 2009; Nguyen et al. 2015).”
BackgroundSMITH, S., & NICHOLS, T. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2008.03.061 · Cited by 5,250 · see citing works
Large-scale brain networks and psychopathology: a unifying triple network model
Menon, V. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.08.003 · Cited by 4,168 · see citing works
Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., Markowitz, J. C., Ninan, P. T., Kornstein, S., Manber, R., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01866-8 · Cited by 3,829 · see citing works
Toward the future of psychiatric diagnosis: the seven pillars of RDoC
Cuthbert, B. N., & Insel, T. R. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-126 · Cited by 3,053 · see citing works
Subgenual prefrontal cortex abnormalities in mood disorders
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997) · Nature · doi:10.1038/386824a0 · Cited by 2,693 · see citing works
Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., Reiss, A. L., & Schatzberg, A. F. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.020 · Cited by 2,214 · see citing works
Drevets, W. C., Price, J. L., & Furey, M. L. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0189-x · Cited by 2,209 · cited 4× · see citing works
“…paradigms, neuroimaging research in MDD has identified disturbances in brain circuits modulating emotional behaviour, encompassing ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), insula and closely related subcortical structures (Anand et al. 2005; Drevets et al. 2008a).”
BackgroundMethodInfluentialEmotion elicitation using films
Gross, J. J., & Levenson, R. W. (1995) · Cognition & Emotion · doi:10.1080/02699939508408966 · Cited by 2,179 · see citing works
Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000446107 · Cited by 1,196 · see citing works
The subgenual anterior cingulate cortex in mood disorders
Drevets, W. C., Savitz, J., & Trimble, M. (2008) · CNS Spectrums · doi:10.1017/s1092852900013754 · Cited by 1,109 · see citing works
The role of default network deactivation in cognition and disease
Anticevic, A., Cole, M. W., Murray, J. D., Corlett, P. R., Wang, X.-J., & Krystal, J. H. (2012) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2012.10.008 · Cited by 978 · see citing works
Anand, A., Li, Y., Wang, Y., Wu, J., Gao, S., Bukhari, L., Mathews, V. P., Kalnin, A., & Lowe, M. J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.02.021 · Cited by 787 · see citing works
Whole brain resting-state analysis reveals decreased functional connectivity in major depression
Veer, I. M. (2010) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2010.00041 · Cited by 753 · see citing works
Reliability of cortical activity during natural stimulation
Hasson, U., Malach, R., & Heeger, D. J. (2009) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2009.10.011 · Cited by 597 · see citing works
Emotions promote social interaction by synchronizing brain activity across individuals
Nummenmaa, L., Glerean, E., Viinikainen, M., Jääskeläinen, I. P., Hari, R., & Sams, M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206095109 · Cited by 538 · see citing works
Resting-state functional connectivity in treatment-resistant depression
Lui, S., Wu, Q., Qiu, L., Yang, X., Kuang, W., Chan, R. C. K., Huang, X., Kemp, G. J., Mechelli, A., & Gong, Q. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10101419 · Cited by 336 · see citing works
Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders
Myers-Schulz, B., & Koenigs, M. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.88 · Cited by 333 · see citing works
Walter, M., Henning, A., Grimm, S., Schulte, R. F., Beck, J., Dydak, U., Schnepf, B., Boeker, H., Boesiger, P., & Northoff, G. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.39 · Cited by 306 · see citing works
Biological parametric mapping: A statistical toolbox for multimodality brain image analysis
Casanova, R., Ryali, S., Baer, A., Laurienti, P. J., Burdette, J. H., Hayasaka, S., Flowers, L., Wood, F., & Maldjian, J. A. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.09.011 · Cited by 302 · see citing works
Kross, E., Davidson, M., Weber, J., & Ochsner, K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.019 · Cited by 295 · cited 1× · see citing works
“In particular, subgenual ACC (sACC) and vmPFC are frequently reported to present altered activation and functional connectivity in depression (Drevets et al. 1997; Zald et al. 2002; Greicius et al. 2007; Kross et al. 2009; Walter et al. 2009; Myers-Schulz & Koenigs, 2012).”
BackgroundThe burden of severe depression: A review of diagnostic challenges and treatment alternatives
Nemeroff, C. B. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.05.008 · Cited by 295 · see citing works
Bluhm, R., Williamson, P., Lanius, R., Théberge, J., Densmore, M., Bartha, R., Neufeld, R., & Osuch, E. (2009) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2009.02030.x · Cited by 294 · see citing works
Horn (2010) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2010.00033 · Cited by 276 · see citing works
Anterior temporal lobe degeneration produces widespread network-driven dysfunction
Guo, C. C., Gorno‐Tempini, M. L., Gesierich, B. G., Henry, M. L., Trujillo, A. J., Shany‐Ur, T., Jovicich, J., Robinson, S., Kramer, J. H., Rankin, K. P., et al. (2013) · Brain · doi:10.1093/brain/awt222 · Cited by 230 · see citing works
Self-citationA preliminary study of functional connectivity in comorbid adolescent depression
Cullen, K. R., Gee, D. G., Klimes‐Dougan, B., Gabbay, V., Hulvershorn, L. A., Mueller, B. A., Camchong, J., Bell, C. J., Houri, A. K., Kumra, S., et al. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.05.022 · Cited by 226 · see citing works
Sliz, D., & Hayley, S. P. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00323 · Cited by 224 · see citing works
Issues for DSM-5: Whither Melancholia? The Case for Its Classification as a Distinct Mood Disorder
Parker, G. B., Fink, M., Shorter, E., Taylor, M. A., Akiskal, H. S., Berríos, G. E., Bolwig, T. G., Brown, W. A., Carroll, B. J., Healy, D., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09101525 · Cited by 212 · see citing works
Self-citationRegional cerebral metabolism associated with anxiety symptoms in affective disorder patients
Osuch, E. A., Ketter, T. A., Kimbrell, T. A., George, M. S., Benson, B. E., Herscovitch, M. W. W., & Post, R. M. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00920-3 · Cited by 196 · see citing works
Defining nodes in complex brain networks
Stanley, M. L., Moussa, M. N., Paolini, B., Lyday, R. G., Burdette, J. H., & Laurienti, P. J. (2013) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2013.00169 · Cited by 194 · see citing works
Liao, X., Xia, M., Xu, T., Dai, Z., Cao, X., Niu, H., Zuo, X., Zang, Y., & Yong He, A. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.07.058 · Cited by 188 · see citing works
Zald, D. H., Mattson, D. L., & Pardo, J. V. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042457199 · Cited by 186 · see citing works
Defining Melancholia: Properties of a Refined Sign-Based Measure
Parker, G. B., Hadži-Pavlović, D., Wilhelm, K. A., Hickie, I. B., Brodaty, H., Boyce, P. M., Mitchell, P. B., & Eyers, K. (1994) · The British Journal of Psychiatry · doi:10.1192/bjp.164.3.316 · Cited by 185 · see citing works
Self-citationNatural Scenes Viewing Alters the Dynamics of Functional Connectivity in the Human Brain
Betti, V., Penna, S. D., de Pasquale, F., Mantini, D., Marzetti, L., Romani, G. L., & Corbetta, M. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.022 · Cited by 183 · see citing works
Local cortical thinning links to resting-state disconnectivity in major depressive disorder
van Tol, M., Li, M., Metzger, C., Hailla, N., Horn, D. I., Li, W., Heinze, H. –., Bogerts, B., Steiner, J. H., He, H., et al. (2013) · Psychological Medicine · doi:10.1017/s0033291713002742 · Cited by 123 · see citing works
Degradation of emotion processing ability in corticobasal syndrome and Alzheimer’s disease
Kumfor, F., Sapey‐Triomphe, L., Leyton, C. E., Burrell, J. R., Hodges, J. R., & Piguet, O. (2014) · Brain · doi:10.1093/brain/awu246 · Cited by 100 · see citing works
Nguyen, V. T., Breakspear, M. J., Hu, X., & Guo, C. C. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.08.078 · Cited by 90 · see citing works
Self-citationAltered functional connectivity density in major depressive disorder at rest
Zhang, B., Li, M., Qin, W., Demenescu, L. R., Metzger, C. D., Bogerts, B., Yu, C., & Walter, M. (2015) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-015-0614-0 · Cited by 62 · see citing works
Measuring melancholia: the utility of a prototypic symptom approach
Parker, G. B., Fletcher, K., Hyett, M. P., Hadži-Pavlović, D., Barrett, M., & Synnott, H. (2008) · Psychological Medicine · doi:10.1017/s0033291708004339 · Cited by 36 · see citing works
Self-citationFinding a biosignature for melancholic depression
Day, C. V., & Williams, L. M. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.72 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression
Stephan, K. E., Manjaly, Z. M., Mathys, C. D., Weber, L. A. E., Paliwal, S., Gard, T., Tittgemeyer, M., Fleming, S. M., Haker, H., Seth, A. K., et al. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00550 · Cited by 437 · see citing works
“For the ACC in particular, this possibility draws support from neuroimaging investigations that have provided evidence for a role of ACC in metacognitive functions such as performance monitoring and conflict detection (Carter et al., 1998; Botvinick et al., 1999).”
BackgroundInfluentialSun, X., Sun, J., Lu, X., Dong, Q., Zhang, L., Wang, W., Liu, J., Ma, Q., Wang, X., Wei, D., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.05.021 · Cited by 129 · see citing works
Li, X., & Wang, J. (2021) · Brain Imaging and Behavior · doi:10.1007/s11682-020-00299-2 · Cited by 89 · see citing works
Nugent, A. C., Ballard, E. D., Gilbert, J. R., Tewarie, P. K., Brookes, M. J., & Zarate, C. A. (2020) · NeuroImage: Clinical · doi:10.1016/j.nicl.2020.102378 · Cited by 34 · see citing works
Zhang, J., Yang, J., Han, D., Zhao, X., Ma, J., Ban, B., Zhu, X., Yang, Y., Cao, D., & Qiu, X. (2018) · Scientific Reports · doi:10.1038/s41598-018-31530-2 · Cited by 11 · see citing works
- Authors
- Guo, C. C., Hyett, M. P., Nguyen, V. T., Parker, G. B., & Breakspear, M. J.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- Black Dog Institute (AU)
- Corresponding author
- Guo, C. C.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2016-02-18
- Volume
- 46
- Issue
- 7
- Pages
- 1535-1545
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2325655614
- Cited by
- 45
- References
- 42
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 11 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 3
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- melancholia, major depressive disorder, depression subtypes, functional connectivity, default mode network, subgenual anterior cingulate cortex, anterior cingulate cortex, posterior cingulate cortex, ventromedial prefrontal cortex, superior temporal gyrus, anhedonia, resting state, deep brain stimulation
- MeSH terms
- Adult, Aged, Cerebral Cortex, Depressive Disorder, Major, Major Depressive Disorder, Depressive Disorder, Emotions, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Young Adult, Connectome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
