Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk
Abstract
:1. Introduction
2. Material and Methods
3. Vitamin D
3.1. Vitamin D Sources and References Levels
3.2. Vitamin D Metabolism
3.3. Vitamin D Is a Bioactive Agent in the Brain
4. Depression: A Significant Risk Factor for Suicide and Suicide Attempt
4.1. Neurological Mechanisms Associated with Depression and Suicide
4.2. Inflammatory Mechanisms Associated with Depression and Suicide
5. Vitamin D, Depression, and Suicide: Interrelated Evidence and Mechanisms
5.1. Sun and Depression
5.2. Vitamin D Levels, Depression, and Suicide
Author, Year | Country; N; Age | Objective(s) | Vitamin D Measure | Depression Measure | Suicidal Behavior | Additional Outcomes | Results/Conclusion |
---|---|---|---|---|---|---|---|
Grudet et al., 2014 [90] | Sweden; 59 suicide attempters (25 men and 34 women): non-suicidal depressed patients (n = 17) and healthy controls (n = 14); 18–73 years old | Asses the association between suicide attempt, vitamin D, and inflammatory changes | Calcidiol was measured in plasma using liquid chromatography–mass spectrometry (LC–MS) | Diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) as schizoaffective disorder (n = 2), Psychotic Disorder (n = 1), Major Depressive Disorder (n = 10), Bipolar I Disorder (n = 3), Bipolar II Disorder (n = 12), Anxiety disorder (n = 4), Generalized Anxiety Disorder (n = 1), Dysthymic Disorder (n = 4), Alcohol Dependence (n = 6), Substance Dependence (n = 2), Adjustment Disorder (n = 7), Adjustment Disorder with Depressed Mood (n = 3), and Depressive Disorder | Suicide attempt | Vitamin D’s association with plasma IL-1β, IL-6, and TNF-α | In comparison to depressed non-suicidal patients and healthy controls, patients with suicide attempts had significantly lower mean vitamin D levels. Clinically, 58% of the suicide attempters had vitamin D deficiency. Increased levels of IL-6 and IL-1β in the blood were associated with low vitamin D. A deficiency in vitamin D was found in suicide attempters. The results suggest this deficiency might contribute to higher proinflammatory cytokines previously found in suicidal individuals. |
Il Park et al., 2016 [92] | Republic of Korea; 15,695 subjects; 20 years and older | Explore the relationship among depressive symptoms, suicidal ideation, and vitamin D in a representative sample of the general population | Serum calcidiol levels were measured by radioimmunoassay (DiaSorin, Stillwater, MN, USA) using a gamma counter (1470 Wizard; Perkin Elmer) | Depressive symptoms (“yes” vs. “no”) were evaluated by asking, “Have you felt so sad or hopeless for at least two consecutive weeks during the past year that you had difficulty performing your usual activities?” | Self-reported information about suicidal ideation (‘‘yes’’ vs. ‘‘no’’) was evaluated by asking, “Did you ever feel like committing. suicide during the past year?” | Sociodemographic and health-related factors | No significant differences in serum 25-hydroxyvitamin D concentrations were found among depressive symptoms and suicidal ideation. Vitamin D, depressive symptoms, and suicidal ideation were not significantly associated. Further studies could help elucidate further the association or lack of association between vitamin D, depressive symptoms, and suicidal ideation. |
Grudet et al., 2020 [24] | USA; 48 un-medicated major depressive disorder (MDD) subjects and 54 healthy controls; 39.3 ± 14.9 years old | Asses the association between suicide ideation, vitamin D, and inflammatory markers in patients with MDD | Analyses of calcidiol were conducted by liquid chromatography–mass spectrometry, model Sciex API 4000 LC/MS/MS | The Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID); clinical interview with a board-certified psychiatrist. Depression severity: 17-item version of the Hamilton Depression Rating Scale (HDRS). | MDD subjects were categorized as “non-Suicidal Ideation group” or “Suicidal Ideation group” based on their HDRS suicidality item score. Subjects indicating a suicide attempt or current suicidal intent within the past week were excluded from the study. | Inflammatory markers IL-6 and TNF-α, neutrophil-to-lymphocyte ratio (NLR), and white blood cell count (WBC) | Patients with MDD with and without suicidal ideation (SI) did not display significant differences in calcidiol levels when compared between them and controls. All the measured inflammatory markers were negatively correlated with calcidiol; these correlations were more significant in MDD subjects, especially in the SI group. Even though calcidiol levels did not discriminate MDD with or without SI or vs. controls, indicators of immune activation in MDD were associated with lower calcidiol, particularly in cases with SI. |
Grudet et al., 2022 [18] | Sweden; 202 patients and 41 healthy Controls; 18–77 years old | (a) Compare calcidiol levels between clinically depressed individuals with insufficient treatment response and healthy controls; (b) assess the association between different affective disorder diagnoses, grade of suicidal ideation, and calcidiol levels | Analyses of calcidiol were conducted by liquid chromatography–mass spectrometry, model Sciex API 4000 (LC/MS/MS) | Diagnosis made according to the DSM-IV-TR; International Neuropsychiatric Interview (MINI) 6.0; SCID-II. Current psychiatric symptoms were assessed using the Comprehensive Psychopathological Rating Scale (CPRS), and the Montgomery-Åsberg Depression Rating Scale (MADRS) was extracted. Patients were divided into four groups based on their diagnosis: major depressive disorder (MDD) single episode (n = 17), MDD recurrent episode (n = 101), chronic MDD (n = 59), or dysthymia (n = 18). | Suicidal ideation (SI) was assessed by the Suicide Assessment Scale (SUAS-S). Subjects are divided into high-grade suicidal ideation and low-grade suicidal ideation. | Patients with depression that had not remitted with previous and ongoing treatments at the moment of the study had significantly lower levels of calcidiol than healthy controls. Only 5% of the controls were calcidiol deficient (<50 nmol/L), while 30% of the depressed patients were. The odds of being depressed decreased 17% per 10 nmol/L increase of calcidiol, which is significant. Symptom severity in dysthymic patients correlated with calcidiol but not in other groups. No significant differences were found in mean calcidiol levels between the four affective disorder diagnoses groups. | |
Calderon-Espinoza et al., 2022 [91] | Mexico; 72 patients were classified into three groups according to their vitamin D levels; 50.6 ± 12.76 years old | Determine the frequency of depression, anxiety symptoms, and suicidal risk or ideation, and associate it with vitamin D serum levels in patients with rheumatoid arthritis | Vitamin D quantification was determined using the chemiluminescence immunoassay technique (Liaison 25-OH Vitamin D Total Assay, Stillwater, MN) | Hospital Anxiety and Depression Scale (HADS) | Spanish adaptation of the self-applied Plutchik scale | Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Rheumatoid Arthritis Quality-of-Life Questionnaire, e-Health Assessment Questionnaire–Disability Index (HAQ–DI) | The Plutchik score and suicidal risk were inversely correlated with inadequate vitamin D levels but not with the Hospital Anxiety and Depression Scale. Higher scores on the Rheumatoid Arthritis Quality-of-Life Questionnaire were associated with suicidal ideation. Inadequate vitamin D serum levels correlated with a Plutchik low correlation coefficient. Regarding the covariance analysis, vitamin D levels persist associated with decreasing suicide ideation. |
5.3. Vitamin D and Neurological Mechanisms Associated with Depression and Suicide
Author, Year | Country; N; Age | Objective | Vitamin D Measure | Depression Measure | Intervention | Additional Outcomes | Results/Conclusion |
---|---|---|---|---|---|---|---|
Lansdowne et al., 1998 [95] | Australia; 44 healthy students; 18 to 43 years old | Test the efficiency of vitamin D supplementation on participants’ mood during winter | No measurement | The Positive and Negative Affect Schedule (PANAS) was used as a self-report measure of positive affectivity (PA) and negative affectivity (NA) | Subjects were given 400 IU, 800 IU, or no vitamin D3 for five days during late winter in a random double-blind study | None | Both doses (400 IU and 800 IU) increased their reported PA by almost a full standard deviation above their population mean. NA did not decrease significantly for either dose group compared to the placebo. Even though it did not reach significance, the trend for NA was a decrease in both dose groups. The placebo group remained practically matched the population means. |
Hoogendijk et al., 2008 [94] | The Netherlands; 1282 residents; 65 to 95 years old | Explore if there is an association between altered calcidiol and parathyroid hormone (PTH) levels and depression | Serum calcidiol concentration was determined using a competitive binding protein assay (Nichols Institute Diagnostics Inc, San Juan Capistrano, California) | Depression was measured using self-reports (Centre for Epidemiologic Studies–Depression scale) and diagnostic interviews (Diagnostic Interview Schedule) | None | Potentially confounding factors and explanatory factors were also measured | Compared to 1087 control individuals, calcidiol levels were 14% lower in 169 persons with minor depression, whereas their PTH was 5% higher. Twenty-six persons with MDD also had a lower calcidiol level by 14% and higher PTH by 33%. Decreased serum calcidiol levels and increased serum PTH levels were significantly associated with depression severity (Center for Epidemiologic Studies Depression Scale). |
Jorde et al., 2008 [96] | Norway; 441 subjects (BMI 28–47 kg/m); 21–70 years old | Serum calcidiol was determined by immunometric (electrochemiluminescence) using an automated clinical chemistry analyzer (Modular E170; Roche Diagnostics®) | Depressed mood was judged with the Beck Depression Inventory (BDI) at inclusion and the end of the study | 20,000 or 40,000 IU vitamin D per week or placebo for one year in a random double-blind study | Blood samples were drawn for analysis of serum calcium, creatinine, and parathyroid hormone (PTH) | Patients with < 40 nmol L(-1) calcidiol levels had significantly more depressive traits as measured by the total and subscales of the BDI than patients with serum levels ≥ 40 nmol L(-1) calcidiol levels. The BDI scores improved significantly after one year in both groups with vitamin D supplementation but not in the placebo group. | |
Kaviani et al., 2020 [23] | Iran; 56 subjects with mild to moderate depression and no other psychiatric disorder; 18–60 years old | Assess the effects of vitamin D supplementation on consequent serum calcidiol, depression severity, and serotonin and oxytocin in patients with mild to moderate depression | The enzyme immunoassay (EIA) method was employed for assessing serum calcidiol (Euroimmun EIA kit, Lubeck, Germany) | Structural clinical diagnostic interview based on the DSM–IV criteria and Beck Depression Inventory-II (BDI-II) score | 50,000 IU cholecalciferol/2 weeks and control (placebo) in an 8-week double-blind, randomized clinical trial | Intact parathormone (iPTH), serum oxytocin, and platelet serotonin | After eight weeks, significant changes in the calcidiol concentrations and BDI-II scores were observed in the intervention group compared to the controls. Differences between groups were not significant for oxytocin and serotonin, but oxytocin concentrations were significantly reduced in controls, and platelet serotonin increased more in controls. |
Rhee et al., 2020 [104] | Republic of Korea; 1736 subjects; 19 to 76 years old | Explore the association between specific domains of depressive symptoms and serum calcidiol concentrations by each sex | 25-Hydroxyvitamin D 125I RIA Kit (DiaSorin, Stillwater, MN, USA) using a 1470 WIZARD Gamma Counter (PerkinElmer, Turku, Finland) | Patient Health Questionnaire-9 (PHQ-9) | None | Other covariates such as sociodemographic information, lifestyle behaviors, and health factors | Log-transformed serum calcidiol concentrations and total PHQ-9 scores were associated significantly only in men after adjusting for various covariates. Moreover, the association between the cognitive and affective subscales and the serum calcidiol concentrations was significant only in men. No association was found in the somatic subscale. |
5.4. Vitamin D and Inflammatory Mechanisms Associated with Depression and Suicide
6. Relationship between VDR Gene, Depression, and Suicide
7. Vitamin D Supplementation for the Treatment of Depression
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
1,25(OH)2D | calcitriol |
25(OH)D | calcidiol |
7-DHC | 7-dehydrocholesterol |
ACC | anterior cingulate cortex |
BBB | blood-brain barrier |
BDNF | brain-derived neurotrophic factor |
CRP | C-reactive protein |
CYP27B1 | 25-hydroxyvitamin D-1 alpha hydroxylase |
CYP2R1 | 25-hydroxylase |
DBP | vitamin D binding protein |
dlPFC | dorsolateral prefrontal cortex |
HPA | hypothalamic–pituitary–adrenal |
IDO | indoleamine 2,3-dioxygenase |
IL | interleukin |
KYN | kynurenine |
LPS | lipopolysaccharide |
MAO-A | monoamine oxidase-A |
MDD | major depressive disorder |
NF-κB | nuclear factor κB |
NGF | nerve growth factor |
NLR | neutrophile-to-lymphocyte ratio |
NT | neurotrophin |
QUIN | quinolinic acid |
RCT | randomized clinical trials |
RXR | retinoid X receptor |
SAD | seasonal affective disorder |
SERT | serotonin reuptake transporter |
SSRI | selective serotonin reuptake inhibitors |
TPH2 | tryptophan hydroxylase 2 |
UVB | ultraviolet-B |
VDR | vitamin D receptor |
VDREs | vitamin D response elements |
WBC | white blood cell count |
WHO | World Health Organization |
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Author, Year | Participants | Conclusions |
---|---|---|
Shin et al., 2016 [88] | 52,228 |
|
Dogan-Sander et al., 2021 [107] | 7162 |
|
Nerhus et al., 2016 [108] | 358 |
|
Grudet et al., 2020 [24] | 102 |
|
Grudet et al., 2014 [90] | 90 |
|
Hashash et al., 2019 [106] | 1352 |
|
Calderón-Espinoza et al., 2022 [91] | 72 |
|
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Somoza-Moncada, M.M.; Turrubiates-Hernández, F.J.; Muñoz-Valle, J.F.; Gutiérrez-Brito, J.A.; Díaz-Pérez, S.A.; Aguayo-Arelis, A.; Hernández-Bello, J. Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk. Nutrients 2023, 15, 1765. https://doi.org/10.3390/nu15071765
Somoza-Moncada MM, Turrubiates-Hernández FJ, Muñoz-Valle JF, Gutiérrez-Brito JA, Díaz-Pérez SA, Aguayo-Arelis A, Hernández-Bello J. Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk. Nutrients. 2023; 15(7):1765. https://doi.org/10.3390/nu15071765
Chicago/Turabian StyleSomoza-Moncada, María Montserrat, Francisco Javier Turrubiates-Hernández, José Francisco Muñoz-Valle, Jesús Alberto Gutiérrez-Brito, Saúl Alberto Díaz-Pérez, Adriana Aguayo-Arelis, and Jorge Hernández-Bello. 2023. "Vitamin D in Depression: A Potential Bioactive Agent to Reduce Suicide and Suicide Attempt Risk" Nutrients 15, no. 7: 1765. https://doi.org/10.3390/nu15071765