Inverse association between serum albumin and depressive symptoms among drug-free individuals with a recent suicide attempt

Abstract

Background and aim: Albumin is a protein with multifaceted functions in the human body. According to many studies, lower serum albumin may be associated with depression in various groups of psychiatric and non-psychiatric patients, as well as with attempted suicide. As more severe depressive symptoms have been identified as a reliable risk factor for suicide in patients with high suicide risk, it would be of interest to study whether, the inverse association between depressive symptoms and albumin may exist among patients with attempted suicide. Therefore, the aim of the study was to investigate the possible association between albumin and depressive symptoms among individuals who recently attempted suicide.

Methods: One-hundred twenty-seven individuals with a recent suicide attempt were involved in the study between 1987 and 2001. Albumin was analyzed in serum. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which the Montgomery-Åsberg Depression Rating Scale (MADRS) and the item assessing Apparent sadness were derived.

Results: Only among patients aged ≥45, serum albumin levels were significantly and negatively correlated with total scores of MADRS and the item Apparent sadness (all p values <.00625).

Conclusions: Our findings indicate an inverse association between serum albumin and the severity of depressive symptoms in individuals who attempted suicide, older than 45 years.

Keywords:

• Albumin
• attempted suicide
• MADRS
• depressive symptoms

Introduction

Suicide is a major health issue throughout the world and one of the leading causes of death among young people [1]. One of the most reliable risk factors for completed suicide is a previous suicide attempt [2–4], therefore individuals with a recent suicide attempt are an important group for suicide research and prevention. In order to find new treatments or methods to identify persons with high risk for completed suicide, studying the neurobiological mechanisms underlying attempted suicide is of interest [5]. Despite an extensive search for biomarkers, no reliable one has been found [5]. The mechanisms involved are supposedly complex, involving several interacting biological and psychological systems.

Albumin is a protein with a multifaceted role in the human body [6]. Among others, albumin plays a role as a carrier protein for various steroids, hormones, and fatty acids, as well as a crucial role in maintaining the oncotic pressure. Furthermore, serum albumin appears to be involved in the physiology of inflammation and has been identified as a non-enzymatic antioxidant [7,8].

In addition, several studies have suggested that albumin in serum may be involved in the pathophysiology of depression. Among others, patients with major depressive disorder (MDD) appear to have lower serum albumin levels compared to controls [9–13], increasing with anti-depressant therapy [8]. Lower serum albumin levels have also been linked to more severe depressive symptoms in various cohorts of patients with non-psychiatric diseases like stroke, HIV, multiple sclerosis (MS), chronic kidney disease, hemodialysis patients, hypertension or cancer [10,12–22]. Interestingly, according to several studies, the negative association between serum albumin and depressive symptoms may be independent of immunological markers like CRP and IL-6 [14–22]. However, this association between symptoms of depression and low albumin seems to be a part of a dysregulation oxidative stress [8]. There is also evidence for the relationship between lower serum albumin levels and depressive symptoms among patients with schizophrenia [23]. However, there are also contradictory, non-significant findings, reported in younger individuals aged <45 years [24–27].

Having depressive symptoms is an important risk factor for suicide, not only in patients with MDD but with various diagnoses like schizophrenia or alcohol dependence [2,28,29]. This is interesting, as there is some evidence for the relationship between lower albumin levels and attempted suicide [30], which is an important risk group for completed suicide [2–4]. These findings, taken together with the well-replicated negative association between depressive symptoms and albumin [10,12–23], raise the issue whether there may be an association between albumin and depressive symptoms among individuals with a recent suicide attempt. Therefore, we aimed in this study to investigate the association between more severe depressive symptoms an important risk factor for suicide [2,28,29] and serum albumin among patients with attempted suicide. As both attempted suicide and the severity of depressive symptoms are risk factors for suicide [2,28,29] appearing to be independent of the clinical diagnosis, we chose to investigate the association between albumin and depressive symptoms regardless of psychiatric diagnoses.

Methods

Subjects

One-hundred twenty-three Swedish patients were recruited shortly after a suicide attempt at the University Hospital in Lund between 1987 and 2001. Suicide attempts were defined as ‘those situations in which a person has performed an actually or seemingly life-threatening behavior with the intent of jeopardizing his/her life, or to give the appearance of such an intent but which has not resulted in death’ [31]. Exclusions criteria were the following: (1) discharge before information and consent about the study, (2) urgent need for psychiatric treatment (i.e. psychotic symptoms or severe depressive symptoms and therefore washout not possible). Psychiatric diagnoses were set by consensus of 2 trained psychiatrists who independently diagnosed the patients according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) [32]. The patients did not receive any anti-depressant or anti-psychotic medication, ADHD medication or mood stabilizer during a washout period of 15 ± 2 days (mean ± SD) after the suicide attempt. Occasional doses of benzodiazepines were allowed; however, no patient received any benzodiazepine for at least 9 h before the blood sample was taken. At the end of the washout period, serum was collected in a standardized manner described earlier after one night of fasting and rest in bed. [33]. On the day of the lumbar punctures, participants were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) [34]. We used the Montgomery–Åsberg Depression Rating Scale (MADRS) consisting of 10 of the items derived from the CPRS [35], as well as the item 41, Apparent sadness, assessing the objective symptom of depressive state. All items were rated from 0 to 6. Albumin concentrations were determined in serum (S-albumin) by electro-immunoassays [36].

All patients were subjected to a general physical examination, including measurement of height and weight in order to calculate the body-mass index (BMI). A complete medical history was taken, including questions about current, as well as smoking status. No patient had a severe medical illness (like autoimmune disease, cancer and kidney disease). The study was approved by the Lund University Medical Ethics Committee. All participants gave their informed consent to participate in the study (LU14-1988). Clinical and demographic characteristics of the sample are presented in Table 1.

Table 1. Demographic, clinical and biological variables of the sample.

	All patients
N	127
Males/Females	61/66
Age	38.1 ± 13.3
BMI
S-albumin g/l	23.9 ± 4.0
MADRS	40.3 ± 5.5
Apparent sadness	17.2 ± 5.6
Axis I diagnoses	1.48 ± 0.71
Mood disorders	71
Anxiety disorders	4
Psychotic disorders	5
Adjustment disorders	27
Substance use disorders	11
Other diagnoses	4
No diagnosis	5

BMI: body-mass index; S: serum; MADRS: Montgomery–Åsberg Depression Rating Scale; Interval data are presented as mean ± standard deviation.

Statistics

All statistical analyses were made using IBM SPSS Statistics 21.0. Since data regarding MADRS were not normally distributed even after log-transformation, we used only non-parametric tests. To test correlations between linear data, the Spearman’s rank order correlation was used. As we had a priori hypotheses of a negative association between albumin and depressive symptoms, one-tailed level of significance was used for these analyses. For remaining statistical analyses we used two-tailed level of significance. Alpha-level of significance was set at p < .05. As age and gender significantly affected albumin concentrations, we tested our hypothesis in subgroups according to age such as patients aged ≥45 (middle aged and old aged according to DSM-IV) [37] and patients aged <45 (young adults according to DSM-IV) [37], as well as, gender such as females and males. To reduce the risk of obtaining false-positive results, Bonferroni correction was used for sub-group analyses.

Results

S-albumin in relation to gender, age, BMI, washout period and smoking

Males had significantly higher serum albumin (p < .001) compared to females in all patients. There was a significant correlation between age and S-albumin (p = .001). S-albumin was not significantly associated with BMI, the length of washout period, or smoking status (n = 95) (all p values >.05).

S-albumin in relation to MADRS and CPRS item 41 – Apparent sadness

In all patients, no significant association was observed between S-albumin, total scores of MADRS or the CPRS item 41 – Apparent sadness (Table 2). With subgroup analyses, we used the Bonferroni corrected p value <.00625. According to this p value, no significant association between S-albumin, total scores of MADRS or the item 41 – Apparent sadness was observed in subgroups divided by gender or in the subgroup of patients aged <45 (Table 2). Among patients aged ≥45, S-albumin were significantly correlated with total scores of MADRS and CPRS item 41 – Apparent sadness according to the Bonferroni corrected p value <.00625 (Table 2).

Table 2. Correlations between S-albumin, total scores of MADRS and the CPRS item Apparent sadness in all patients and in subgroups according to gender and age.

	MADRS		Apparent sadness
	rs	p	rs	p
S-albumin
All patients (n = 127)	0.025	.391	0.023	.398
Females (n = 66)	0.091	.236	0.034	.396
Males (n = 61)	0.049	.355	0.010	.468
Aged ≥45 (n = 36)	−0.452	<.003	−0.513	<.001
Aged <45 (n = 91)	0.145	.085	0.242	.008

MADRS: Montgomery–Åsberg Depression Rating Scale; S: serum. One-tailed level of significance was used. Bonferroni corrected p value was set at <.00625 with subgroup analyses. Significant results are highlighted in bold.

Discussion

We found that lower serum albumin levels were significantly and negatively associated with depressive symptoms measured by the MADRS, as well as the CPRS item 41 – Apparent sadness, assessing the objective symptom of the depressive state in the subgroup of individuals with attempted suicide, aged ≥ 45. This is, to the best of our knowledge, the first study to investigate associations between the severity of depressive symptoms and serum albumin among individuals with attempted suicide.

Similarly to our findings, several previous studies from various groups of patients with psychiatric or somatic diseases have suggested an inverse relationship between serum in albumin and depressive symptoms [10,12–22]. Some studies have however shown non-significant results [24–27]. These have been performed mainly in younger subjects (aged <45 years), which is in line with our finding of significant results only in subjects aged >45years.

There are several possible rationales for an association between albumin and symptoms of depression. Firstly, it is possible that lower albumin may contribute to the dysregulation of oxidative stress which is seen in patients with depression including higher free radicals and oxidative damage products [8]. This effect may be due to that serum albumin is considered the main extracellular molecule responsible for maintaining the plasma redox state. Secondly, serum albumin is a transporter and depot protein for fatty acids including omega-3 polyunsaturated fatty acids which is interesting as deficiency of omega-3 polyunsaturated fatty acids has been linked to both depression and suicidal behavior [38,39]. Thirdly, serum albumin is a carrier protein for other molecules as fatty acids like magnesium ion or thyroid hormones, which all can affect the symptomatology of depression [37,40]. Furthermore, serum albumin is involved in the inflammatory system, decreasing with increased inflammation, and inflammatory markers are known to be associated with depressive disorder and attempted suicide [41,42]. Thus, the low albumin levels could be a result of depression with inflammatory markers. However, according to some works, the correlation between lower serum albumin and depressive symptoms were independent of immunological markers like CRP and IL-6 [14–22].

We only found an association between albumin levels and depressive symptoms in older adults (aged ≥45 years). This is actually consistent with many of the previous studies reporting a significant association, since samples investigated mainly have had mean age of >40 years [10,12–22,43], while studies on samples aged <40 years predominantly did not observe any significant association between albumin and depressive symptoms [24–27].

There are several limitations to the study. The most important limitation is the small sample size and the absence of healthy controls. However, the depressive symptoms experienced by individuals with a recent suicide attempt is of a magnitude that makes them unsuited to compare with healthy individuals, in order to detect within-group differences. Another limitation is that we could not perform any analyses of covariance as data regarding MADRS was not normally distributed, even after log-transformation. However, we performed statistical analyses for subgroups according to age and gender. Another limitation is that we had no data about kidney function, for example, glomerular filtration rate which has importance for serum albumin levels [44].

Our findings may have some indications for future research. For example, the question could be raised whether the measurement of serum albumin could be used as an objective marker for the assessment of symptoms severity of depressive symptom, as well as suicide risk among individuals who attempted suicide and older than 45 years.

In conclusion, our findings suggest that lower serum albumin is associated with more severe depressive symptoms in individuals with a recent suicide attempt, aged ≥45 years. Future studies can further examine and clarify the relationship between albumin and depressive symptoms regarding attempted suicide.

Disclosure statement

No potential conflict of interest was reported by the authors.