Default mode dysfunction underpins suicidal activity in mood disorders
Abstract
Background: Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention. Method: Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity. Results: Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA. Conclusions: DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.
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These studies have mostly assessed suicide risk in larger clinical samples of participants diagnosed with mood disorders and other psychiatric conditions with which suicide is a comorbid phenotype, but rarely have they investigated suicide transdiagnostically.
“Finally, these studies have mostly assessed suicide risk in larger clinical samples of participants diagnosed with mood disorders (64–75) and other psychiatric conditions (76–79) with which suicide is a comorbid phenotype, but rarely have they investigated suicide transdiagnostically.”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [73]
A resting-state study of large-scale brain networks in suicide attempters compared to non-attempters found that increased posterior default mode network connectivity was associated with recent suicidal activity in attempters; attempters also had greater midline circuitry activity and differential basal ganglia and default mode network co-activity.
“A resting-state study of large-scale brain networks in suicide attempters compared to non-attempters found that increased posterior default mode network connectivity was associated with recent suicidal activity in attempters; attempters also had greater midline circuitry activity and differential basal ganglia and default mode network co-activity (73).”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [73]
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Liu, C., Fang, S., Cheng, C., Lin, P., Dong, D., Yao, S., Situ, W., & Wang, X. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111622 · Cited by 2 · see citing works
Schaffer, A., & Malhi, G. S. (2024) · Bipolar Disorders · doi:10.1111/bdi.13442 · Cited by 2 · see citing works
Self-citationHwang, H.-H., Kim, S., Shim, S.-H., & Kim, J. S. (2025) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn-25-0078 · Cited by 1 · see citing works
Zhang, J.-W., Yu, H., He, L., Zhang, R., Lv, H.-Z., Peng, Z.-W., & Wang, Y. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121634 · Cited by 1 · see citing works
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Make news: Suicidal behaviour disorder – A ‘diagnosis’ with good intentions?
Malhi, G. S., & Bell, E. (2019) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867419872533 · Cited by 1 · see citing works
Self-citationNeural bases of suicidal ideation and depression in young college students
López-Ramírez, E., Pérez-Santiago, A. D., Sánchez-Medina, M. ., Matías-Pérez, D., & García-Montalvo, I. A. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1141591 · Cited by 1 · see citing works
Höfels, S. (2025) · BILT Student Research Journal 2025 - Issue 6 · doi:10.70969/20251001 · Cited by 1 · see citing works
Preventing suicide by young people requires integrative strategies
Malhi, G. S., Bell, E., & Mannie, Z. N. (2021) · The Medical Journal of Australia · doi:10.5694/mja2.51367 · Cited by 1 · see citing works
Self-citationThe Ethics of Suicide in Mental Illness: Novel Neuroscientific Perspectives
Malhi, G. S. (2019) · The American Journal of Bioethics · doi:10.1080/15265161.2019.1654021
Self-citationSuicide is indeed more common in serious mental illnesses: Are there neural mediators?
Malhi, G. S., Bell, E., & Mannie, Z. N. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2021.01.011
Self-citationSuicide as a Systemic Disorder
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Neural Timescale of Adolescents Major Depressive DisorderPreprint
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Troubles bipolaires et risque suicidaire
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Neural correlates of decision making and executive function in suicidal thoughts and behaviors
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- Authors
- Malhi, G. S., Das, P., Outhred, T., Bryant, R. A., Calhoun, V., & Mann, J. J.
- Affiliations
- The University of Sydney (AU)
- UNSW Sydney (AU)
- Mind Research Network (US)
- New York State Psychiatric Institute (US)
- Corresponding author
- Malhi, Gin S.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2019-05-30
- Volume
- 50
- Issue
- 7
- Pages
- 1214-1223
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2947576353
- Cited by
- 73
- References
- 41
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 10 · 2021: 13 · 2020: 6 · 2019: 5
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Social Psychology › Mental Health via Writing
- Keywords
- suicide, mood disorders, depression, default mode network, basal ganglia, salience network, frontoparietal network, resting-state functional connectivity, self-referential processing, cognitive flexibility, suicide attempters
- MeSH terms
- Default Mode Network, Adolescent, Adult, Aged, Basal Ganglia, Bipolar Disorder, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Rest, Suicide, Attempted, Case-Control Studies, Mood Disorders, Young Adult, Executive Function, Suicidal Ideation
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