Sex-dependent grades of haematopoietic modulation in patients with major depressive episodes are associated with suicide attempts
Open accessAbstract
Suicide is the leading cause of non-natural death worldwide, and major depressive disorder (MDD) is the mood disorder with the highest prevalence among individuals with suicidal behaviour (SB). The role of inflammation and immunomodulation in mood disorders has raised interest in recent years, as inflammation biomarkers have been reported to be increased in mood disorder patients, suggesting a role of inflammation in their pathogenesis. The influence of inflammation on the haematopoietic production is well known; however, a comprehensive study of the haematopoietic production in patients with major depressive episodes (MDE) is lacking. We examined global haematopoietic parameters from complete blood counts (CBC) of patients with MDE, in search of prognostic patterns. MDE patients presented differences in several CBC parameters, differences that were clearly pronounced and/or significant in concurrence with suicide attempts (SA). Red and white blood cell lineage parameters were affected, suggesting general haematopoietic modulation or imbalance. We observed distinct haematological parameter changes in women versus men, with men presenting milder alterations than women. Interestingly, we found that the List of Threatening Experiences (LTE) score, but not the Childhood Trauma Questionnaire (CTQ), was associated with the haematopoietic alterations observed exclusively in women and, more importantly, served as a parameter to stratify female MDE patients based on concurrence or non-concurrence with SA. In conclusion, grades of haematopoietic modulation in MDE patients are associated with absence or presence of SA. Haematopoietic manifestations differ between men and women and, in the latter, are markedly influenced by late, and not early, traumatic events.
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In Martínez-Botía, Velasco and Rolle et al., MLR was more significantly decreased with suicide attempt than in major depressive disorder without suicide attempt and healthy controls.
“MLR was more significantly decreased with SA than MDD nSA and HC”
In Martínez-Botía, Velasco and Rolle et al., NLR was not statistically significant where found between groups.
“NLR was not statistically significant where found between groups”
In Martínez-Botía, Velasco and Rolle et al., PLR was not statistically significant where found between groups.
“PLR was not statistically significant where found between groups”
Five included studies were conducted in Turkey, one in India, two in Spain, one in Sweden, one in Israel, and one in Thailand.
“Five studies were conducted in Turkey [8, 20, 30–32], one in India [27], two in Spain [4, 29], one in Sweden [28], one in Israel [26], and one in Thailand [9].”
In three other studies, the difference in PLR between patients with a history of SA and those without was not observed.
“Conversely, this difference was not observed in three other studies [20, 29, 32] (Table 2).”
MLR was reported to be decreased in depressed patients with SB vs HC.
“However, MLR was reported to be decreased in depressed patients with SB vs HC [29] (Table 3).”
Inflammatory response is influenced by multiple factors, such as body mass index, use of tobacco and other psychoactive substances, duration and severity of illness, resistance to antidepressant treatment, other psychiatric comorbidities, unbalanced diet, lack of exercise, and stress or traumatic life events in childhood or adulthood.
“However, we also need to keep in mind that inflammatory response is influenced by multiple factors, such as body mass index, use of tobacco and other psychoactive substances, duration and severity of illness, resistance to antidepressant treatment, other psychiatric comorbidities, unbalanced diet, lack of exercise, and stress or traumatic life events in childhood or adulthood [27, 29, 39].”
The phenomenon of clearer PLR difference vs HC might be explained by platelets being one of the first cells to start an inflammatory cascade and patients with depression having a loss of equilibrium in hematopoietic production.
“This phenomenon might be explained by the fact that platelets are one of the first cells to start an inflammatory cascade (cytokines, chemokines, the serotonin pathway), and patients with depression had a loss of equilibrium in hematopoietic production, resulting in an imbalance or distress in modulation [29].”
In two studies, the difference in PLR between depressed patients and HC was not observed.
“Conversely, in two studies, this difference was not observed [20, 29] (Table 3).”
In two studies there was a nonsignificant tendency toward an increase in NLR in patients with a history of SA vs without any.
“First, in two studies there was a (nonsignificant) tendency toward an increase in NLR in patients with a history of SA vs without any [29, 32].”
Three other studies reported no statistically significant differences in NLR between depressed patients with a history of SA and HC.
“However, three other studies reported no statistically significant differences [28, 29, 31] (Table 3).”
The present review found no evidence for a link between MLR and SB in depressed patients; only two studies explored MLR in relation to SB in MDD, with no reported statistically significant differences between depressed patients with and without SB.
“Finally, only two studies explored the MLR index in relation to SB in MDD, with no reported statistically significant differences between depressed patients with and without SB [4, 29] (Table 2).”
The number of studies on the association between NLR, PLR, MLR, and depression is increasing, and different voices have emerged.
“As the number of studies on the association between NLR, PLR, MLR, and depression is increasing, different voices have emerged (46–49).”
From Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio in Depression: An Updated Systematic Review and Meta-Analysis (2022) · cites this paper as [48]
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- Authors
- Martínez-Botía, P., Velasco, A., Rolle, V., Jiménez-Trevino, L., De la Fuente-Tomás, L., Bernardo, Á., Arias, T., Muñoz-Turrillas, M. D. C., García-Alvarez, L., González-Blanco, L., Rodríguez-Revuelta, J., Garcia-Portilla, M. P., Courtet, P., Bobes, J., Gutiérrez, L., & Sáiz, P. A.
- Affiliations
- Universidad de Oviedo (ES)
- Hospital Universitario Central de Asturias (ES)
- Inserm (FR)
- Corresponding author
- Gutiérrez, Laura
- Sáiz, Pilar Alejandra
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 40
- Pages
- 17-30
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W3037628226
- Cited by
- 27
- References
- 46
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 5 · 2021: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Neuropsychopharmacology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- Funders
- Universidad de Oviedo
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive episode, suicide attempts, complete blood count, sex differences, inflammation, immunomodulation, childhood trauma, prognostic factors, suicidal behavior
- MeSH terms
- Adult, Aged, Cross-Sectional Studies, Depressive Disorder, Major, Major Depressive Disorder, Female, Hematopoiesis, Humans, Male, Middle Aged, Sex Characteristics, Suicide, Attempted, Cohort Studies, Principal Component Analysis
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 ›
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