Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression
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Background Mood disorders are associated with the highest increase of attempted and completed suicide. Suicidality in major depressive disorder and in schizophrenia has been associated with reduced gray matter volumes in orbitofrontal cortex. Lithium reduces the suicide risk of patients with bipolar disorder (BD) to the same levels of the general population, and can increase GM volumes. We studied the effect of a positive history of attempted suicide and ongoing lithium treatment on regional GM volumes of patients affected by bipolar depression.Methods With a correlational design, we studied 57 currently depressed inpatients with bipolar disorder: 19 with and 38 without a positive history of suicide attempts, 39 unmedicated and 18 with ongoing lithium treatment. Total and regional gray matter volumes were assessed using voxel-based morphometry.Results Total GM volume is inversely correlated with depression severity. A positive history of suicide attempts was associated with higher stress in early life. Suicide attempters showed reduced GM volumes in several brain areas including dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate, superior temporal cortex, parieto-occipital cortex, and basal ganglia. Long term lithium treatment was associated with increased GM volumes in the same areas where suicide was associated with decreased GM.Conclusions Reduced GM volumes in critical cortical areas of suicidal patients could be a biological correlate of an impaired ability to associate choices and outcomes and to plan goal-directed behaviors based on a lifetime historical perspective, which, coupled with mood-congruent depressive cognitive distortions, could lead to more hopelessness and suicide. Lithium could exert its specific therapeutic effect on suicide by acting in the same areas.
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“Antiapoptotic effects of lithium (226) may increase gray matter volume in the dlPFC, where hypoactivity and cortical thinning are implicated in suicide risk.”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [226]
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Huber, R. S., Subramaniam, P., Kondo, D. G., Shi, X., Renshaw, P. F., & Yurgelun‐Todd, D. A. (2019) · Bipolar Disorders · doi:10.1111/bdi.12729 · Cited by 46 · see citing works
Lippard, E. T. C., Johnston, J. A. Y., Spencer, L., Quatrano, S., Fan, S., Sankar, A., Weathers, J., Pittman, B., Oquendo, M. A., & Blumberg, H. P. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.11.097 · Cited by 44 · see citing works
Gray matter volumetric study of major depression and suicidal behavior
Rizk, M. M., Rubin-Falcone, H., Lin, X., Keilp, J. G., Miller, J. M., Milak, M. S., Sublette, M. E., Oquendo, M. A., Ogden, R. T., Abdelfadeel, N. A., et al. (2019) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2018.11.007 · Cited by 35 · see citing works
Vai, B., Mazza, M. G., Cazzetta, S., Calesella, F., Aggio, V., Lorenzi, C., Zanardi, R., Poletti, S., Colombo, C., & Benedetti, F. (2021) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2021.100254 · Cited by 13 · see citing works
Self-citation
- Authors
- Benedetti, F., Radaelli, D., Poletti, S., Locatelli, C., Falini, A., Colombo, C., & Smeraldi, E.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Benedetti, Francesco
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 135
- Issue
- 1-3
- Pages
- 139-147
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W1979203160
- Cited by
- 165
- References
- 69
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11 · 2023: 6 · 2022: 2 · 2021: 15 · 2020: 18 · 2019: 8 · 2018: 29 · 2017: 11 · 2016: 12 · 2015: 8 · 2014: 18 · 2013: 8 · 2012: 4
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- European Commission (222963)
- Ministero della Salute
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- suicidality, lithium, gray matter volume, bipolar depression, bipolar disorder, suicide attempts, orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, depression severity, early life stress, hopelessness, goal-directed behavior
- MeSH terms
- Adult, Bipolar Disorder, Cerebral Cortex, Decision Making, Depression, Major Depressive Disorder, Depressive Disorder, Major, Depressive Disorder, Female, Goals, Humans, Male, Middle Aged, Organ Size, Suicide, Suicide, Attempted, Case-Control Studies, Prefrontal Cortex, Lithium Compounds, Mood Disorders
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