Background: Some physicians have reported lower serum albumin levels in patients with major depression in Western countries. In this study, the relationship between serum albumin levels and mood disorders (including mania and major depression) was investigated during the acute phases in Taiwanese psychiatric inpatients.
Methods: A review of medical charts during a 1-year period was carried out in a population of 213 Taiwanese psychiatric inpatients that included 61 patients with mood disorders (with or without suicide attempts). The collected data included age, body weight, height, serum albumin levels, and routine blood biochemistry examination results. These data were compared with data from a healthy control group (N=32) drawn from the staff of the psychiatric ward. Statistical analysis was done using covariance after age adjustment.
Results: The mean serum albumin levels were 40.2±4.0 g/L in patients with mania (N=25), 39.8±2.8 g/L in patients with major depression (N=36), and 45.8 ±2.0 g/L in the control group. Patients with mania (F=64.6, p=0.000) and major depression (F=68.9, p=0.000), respectively, had significantly lower albumin levels than the control group after age adjustment. However, for the patients with major depression, no significant difference in serum albumin levels were found between patients who had attempted suicide and those who had not.
Conclusion: Lower serum albumin levels were noted during the acute phases of mania and major depression in Taiwanese psychiatric inpatients.
(Chang Gung Med J 2002;25:509-13)

Key words: albumin, mania, major depression, bipolar disorder, suicide attempt.

The concentration of albumin in plasma is commonly below normal during infections,(1) after injury (including elective surgery) and myocardial infarctions,(2,3) in patients with malignant diseases,(4) and in critically ill patients.(5) The factors which determine the concentrations of circulating proteins include changes in circulating fluid volume, exchange with or loss of the extravascular tissue space, lymphatic return, catabolism, synthesis, and outflow.(6)
Recently, many reports have shown that depression is accompanied by an activation of the immune/inflammatory system, including an acute phase response as indicated by changes in serum acute phase protein.(7-12) Some physicians have reported that lower serum albumin (one of the negative acute phase proteins) levels were noted in patients with major depression in Western countries.(15-20) However, there were no discussions concerning serum albumin levels and patients with mania except for other acute phase proteins.(12-14) Recently, some physicians have also reported that lower serum zinc and albumin concentrations (zinc is closely bound to albumin in peripheral blood) were related to the immune/inflammatory response in patients with major depression.(15,16) Albumin is a metal-binding protein shown to possess free radical scavenging properties, and may thus be a selective antioxidant.(17) Therefore, the role of serum albumin in patients with psychiatric diseases is important and needs to be studied again.
In this study, the relationship between serum albumin levels and mood disorders (including mania and major depression) was investigated during the acute phases in Taiwanese psychiatric inpatients. In addition, the serum albumin levels of patients with major depression were compared between those who had attempted suicide and those who had not.

METHODS

Subjects and design
From January 1995 through December 1995, 213 patients (99 men, 114 women) admitted to the acute psychiatric inpatient unit of the Chang Gung Memorial Hospital in Kaohsiung were included in the study. All medical records were reviewed. The collected data included age, body mass index (BMI), albumin level, suicide attempts on admission, and mood disorders (including mania and major depression) in patients with no other co-morbid illnesses according to DSM-III R criteria. All subjects had normal blood test results, including complete blood count, serum sodium, potassium, blood urea nitrogen, creatinine and alanine aminotransaminase. The control group data came from 32 healthy volunteers (14 men, 18 women) who were members of the staff of the same psychiatric ward.

Laboratory data
Serum albumin levels were detected in the clinical biochemistry laboratory of the Chang Gung Memorial Hospital in Kaohsiung using the bromocresol green method, Hitachi 705 at 37 oC (Albumin Automated Analysis, Wako, Japan) after the patients had fasted for at least 9 hours the morning after admission.(18) The data of the control group were also collected at the same clinical biochemistry laboratory after they had fasted for at least 9 hours.

Statistical analysis
Data were evaluated using analysis of covariance (ANCOVA) after age adjustment for different sex, subtypes, and suicide attempts in mood disorders. All tests were carried out at the 5% alpha level.

RESULTS

In this study, the 213 patients included 106 with schizophrenia, 61 with mood disorders, 10 with organic disorders, 9 with delusion disorders and 11 with other disorders. Six were drug dependent and 10 were alcohol dependent. Of the 61 patients with mood disorders, 25 had mania and 36 had major depression (all patients were unipolar depression and 7 had attempted suicide before admission). The mean age, BMI, and level of serum albumin in patients with mania were 32.7±15.1 years old (mean±standard deviation, SD), 24.4±3.8 kg/m2, and 40.2±4.0 g/L, respectively. The mean age, BMI, and level of serum albumin in patients with major depression were 43.0±17.8 years old, 23.2±3.9 kg/m2, and 39.8±2.8 g/L, respectively. The mean age, BMI and level of serum albumin in control group were 30.1±4.9 years old, 22.2±2.4 kg/m2, and 45.8±2.0 g/L, respectively.
For patients with mania, the mean serum albumin levels in men and women were 40.1±5.0 g/L and 40.3±2.7 g/L, respectively. Analysis of covariance after age adjustment revealed no significant difference in mean serum albumin levels between men and women with mania (F=0.42, p=0.523). For patients with major depression, the mean serum albumin levels in men and women were 39.8±3.0 g/L and 39.8±2.7 g/L, respectively. Analysis of covariance after age adjustment revealed no significant differences in mean serum albumin levels between men and women with major depression (F=0.05, p=0.830).
Analysis of covariance after age adjustment revealed significant difference in the mean serum albumin levels between patients with mania and control subjects (F=64.6, p=0.000). Analysis of covariance after age adjustment also revealed significant difference in mean serum albumin levels between patients with major depression and control subjects (F=68.9, p=0.000).
In addition, for those who had attempted suicide, analysis of covariance after age adjustment revealed no significant difference in the mean serum albumin levels between patients with major depression who had attempted suicide and those who had not. (F=2.6, p=0.117).

DISCUSSION

The results of this retrospective study showed that there were lower serum albumin levels in psychiatric inpatients with mood disorders compared with the control group using analysis of covariance after age adjustment. This suggests that psychiatric inpatients with mood disorders in Taiwan may also suffer systemic responses similar to those noted in Western countries during the acute phase of illness.(7-12,14) It has been suggested that mania or major depression might be accompanied by an immunological or acute-phase protein response.(7-12)
Gabay and Kushner (1999) described conditions that commonly lead to severe changes in the plasma concentration of acute-phase proteins including those found during infection, trauma, surgery, burns, tissue infarction and advanced stage cancer.(19) Moderate changes occur after strenuous exercise, heat stroke, and childbirth.(20,21) Small changes occur after psychological stress and in patients with several types of psychiatric illnesses.(12,19,21,22) Furthermore, no significant difference was noted in the mean serum albumin levels between those with major depression who attempted suicide and those with major depression who did not attempt suicide. This suggests that acute phase proteins results in only small changes in patients with major depression who had attempted suicide, although suicide attempts are thought to be severe behavior in those with psychiatric diseases.
Due to the retrospective nature of this study, severity ratings and nutritional conditions were not available for analysis. The records of intake and course of illness after the first episode were not complete and were therefore not included in this analysis.
There have been reports showing a significant negative correlation between albumin concentrations and severity of illness(10) and lower albumin levels in patients with treatment-resistant depression in Western countries.(23) However, no discussions about the serum albumin levels and patients with mania were included except for other acute phase proteins.(12-14) The finding that serum albumin levels were lower in patients with mania than those in the control subjects in this study may be the first time it has been reported. According to recent studies, interleukin-6 and interleukin-2 are the chief stimulators of the production of most acute-phase proteins.(24,25) The research showed the levels of both soluble interleukin-2 receptor (sIL-2R) and soluble interleukin-6 receptor (sIL-6R) were elevated in patients with major depression. However, Tsai et al. found that Taiwanese patients with manic episodes had increased levels of sIL-2R but not sIL-6R.(26)
It has been demonstrated that the serum albumin concentration may be a prognostic marker for mortality in elderly hospitalized patients,(27) survival in human immunodeficiency virus-infected women,(28) and prognosis of disease in patients with injury or inflammation.(21) Therefore, the level of serum albumin might apply to be a predictive marker for the discussion of the prognosis of drug responses and clinical courses in patients with mood disorders.
The results of this study only provided the preliminary data. The relationship of serum albumin levels and mood disorders needs to be further explored in controlled prospective studies that include larger numbers of patients.

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From the Department of Psychiatry, Chang Gung Memorial Hospital, Kaohsiung.
Received: Jan. 11, 2002; Accepted: Jun. 5, 2002
Address for reprints: Dr. Tiao-Lai Huang Department of Psychiatry, Chang Gung Memorial Hospital. 123, Ta-Pei Road, Niaosung, Kaohsiung, Taiwan, R.O.C. Tel.: 886-7-7311723 ext. 8752; Fax: 886-7-7326817; E-mail: a540520@cgmh.org.tw