INT’L. J. PSYCHIATRY IN MEDICINE, Vol. 48(2) 109-119, 2014
PLASMA GALANIN IS A BIOMARKER FOR SEVERITY OF MAJOR DEPRESSIVE DISORDER* YONG-JUN WANG Tianjin AnDing Hospital, Capital Medical University, Beijing, and Tsinghua Univeristy, Beijing YU-TAO YANG HUI LI Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University PO-ZI LIU Tsinghua University, Beijing CHUAN-YUE WANG Beijing Key Laboratory of Mental Disorders, Capital Medical University ZHI-QING DAVID XU Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University
ABSTRACT
Objective: This study investigated the association between plasma galanin level and depression severity. Methods: The severity of depression symptoms of 79 patients with major depressive disorder (MDD; 52 women and 27 men, 71 patients in onset, 8 in remission) was assessed using the 17-item Hamilton
*This study was supported by the Beijing Municipal Natural Science Foundation of China (ID: 09G0013), Tianjin Health Bureau Technology Fund (ID: 2012KR01, 12KG111), and National Natural Science Foundation of China (ID: 81071083, 31271154, 31171032), Nerve Regeneration and Repair, Beijing Key Laboratory topics (ID: 2012SJZS04), Beijing Center for Neural Regeneration and Repairing (ID: 2012SJZS04), and The National Research Program of China 973 Program (2010CB912003). 109 Ó 2014, Baywood Publishing Co., Inc. doi: http://dx.doi.org/10.2190/PM.48.2.d http://baywood.com
110 / WANG ET AL.
Depression Rating Scale. Venous fasting blood samples (5 mL) were taken from the 79 MDD patients, 35 healthy siblings, and 19 healthy controls, and plasma samples were prepared. Galanin levels in the plasma were measured by radioimmunoassay. Results: Plasma galanin in MDD patients was significantly higher than that of remission patients, healthy siblings, or healthy controls (P < 0.05) There was no significant difference between the healthy sibling and healthy control groups (P = 0.924). Plasma galanin of remission patients was also significantly higher than that of healthy controls (P < 0.05). There was no significant correlation between age and galanin levels in the 79 patients (r = 0.053, P = 0.646), nor was there a correlation between age and galanin levels when patients were stratified by gender (P > 0.05). There was a significant positive correlation between plasma galanin levels and depression severity in women MDD patients (r = 0.329, df = 42, P = 0.020), but not in men patients. Conclusions: Plasma galanin levels may be an important biomarker for depression severity, especially in female patients. (Int’l. J. Psychiatry in Medicine 2014;48:109-119)
Key Words: major depressive disorder, Hamilton Depression Rating Scale, galanin, plasma
INTRODUCTION Major depressive disorder (MDD) is a severe disabling chronic disease that affects the lives of millions worldwide [1]. It is characterized by low mood, lack of enjoyment, pessimistic thinking, and reduced energy [2]. Substantial evidence has implicated dysfunction of brain serotonin (5-hydroxytryptamine [5-HT]) and noradrenaline neurons in the etiology of MDD, but the underlying mechanisms remain unclear [3]. The neuropeptide galanin is widely distributed in the central nervous system and peripheral tissues, and participates in a variety of physiological and pathological processes [4]. In particular, galanin functions to regulate brain 5-HT and noradrenaline in depression [5]. Preclinical data has indicated that galanin is involved in the pathogenesis of MDD [6, 7]. Galanin receptor agonists such as galmic and galnon produce an antidepressant-like effect in the rat [8]. M40 (galanin[1-13]-Pro-Pro[Ala-Leu]2-Ala amide), a galanin receptor antagonist, could act against the antidepressant-like effect of fluoxetine [9]. In a human study, intravenous administration of galanin had fast antidepressant efficacy and affected the sleep electroencephalogram [10]. Polymorphism of the galanin gene was found to be associated with symptom severity in female patients suffering from MDD [11]. However, whether the level of plasma galanin is associated with MDD has not been investigated. In this study, we compared the plasma galanin levels of patients with MDD and healthy controls, and investigated the association between plasma galanin levels and the severity of depression symptoms in men and women MDD patients.
GALANIN AS A MARKER OF MDD SEVERITY /
111
METHODS Study Setting and Subjects This study was conducted at Beijing AnDing Hospital, Capital Medical University, Beijing, between March and October 2009. Outpatients were screened via psychiatric interviews by an experienced researcher in accordance with the guidelines of the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; American Psychiatric Association, 1994). MDD Subjects were eligible if they were not suffering from a major neurological or medical illness. Seventy-nine patients with current MDD were recruited, 52 women (age, 37.8 ± 12.7 years) and 27 men (age, 32.1 ± 10.7 years; Table 1). In addition, the study included 35 healthy siblings of outpatient MDD patients, and 19 healthy controls (employees of the hospital). All subjects were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D). Remission in MDD patients was defined as an HAM-D score of less than 8. The Ethics Committee of Beijing AnDing Hospital, Capital Medical University, approved this study. All subjects signed written informed consent forms before the study. Radioimmunoassay Venous fasting blood samples (5 mL) were collected from the subjects between 8:00 a.m. and 9:00 a.m. directly into evacuated tubes containing ethylenediamine tetraacetic acid. The blood samples were immediately centrifuged at 3,000 rpm for 10 min. Galanin levels in the plasma were detected by radioimmunoassay using a kit (Phoenix Pharmaceuticals, CA) in accordance with the manufacturer’s
Table 1. Demographic Features, HAM-D Scores, HAMA Scores, and Galanin Plasma Levels of MDD Patients
Age (years) Body mass index (kg/m2) Age of onset (years) Galanin (ng/mL) HAM-D HAMA
Men (n = 27)
Women (n = 52)
32.1 ± 10.7 22.4 ± 3.6 27.8 ± 9.6 30.7 ± 8.3 19.5 ± 6.8 17.2 ± 11.8
37.8 ± 12.7 22.6 ± 2.8 31.3 ± 10.1 29.7 ± 7.8 17.8 ± 7.4 15.1 ± 8.4
t = –0.773, P = 0.444 t = 0.259, P = 0.797 t = –1.137, P = 0.262 t = 0.085, P = 0.933 t = 0.999, P = 0.321 t = –0.698, P = 0.489
Note: Data were expressed as mean ± standard deviation; HAM-D, the Hamilton Depression Rating Scale; HAMA, the Hamilton Anxiety Rating Scale.
112 / WANG ET AL.
instructions. The results were analyzed with the SN-695 gamma counter radioimmunoassay program, version 6.0. Statistical analysis Data were analyzed using SPSS version 16 statistical analysis software (SPSS, Chicago, IL). The independent-samples t-test and one-way ANOVA were performed to analyze the differences in galanin plasma levels among MDD patients, healthy siblings, and healthy controls. A P-value of < 0.05 was considered statistically significant. RESULTS Seventy-nine patients with MDD were enrolled in this study, including 52 women and 27 men (Table 1). There were no significant differences in age, age at MDD onset, body mass index, HAM-D score, Hamilton Anxiety Rating Scale (HAMA) score, or plasma galanin levels between men and women patients with MDD. There was a significant difference in plasma galanin among MDD patients, healthy siblings, and healthy controls (F = 34.152, P < 0.001; Table 2). Plasma galanin was higher in episode MDD than in remission, and patients in remission had significantly higher galanin levels than healthy controls (F = 37.372, P < 0.001; Table 3). Table 2. Differences in Plasma Galanin Concentration among MDD Patients, Healthy Siblings, and Healthy Controls
MDD Healthy siblings Healthy controls
n
Galanin (ng/ml)
F
P
79 35 19
31.20 ±10.61a 19.01 ± 1.00b 19.24 ± 2.07
34.152
PLASMA GALANIN IS A BIOMARKER FOR SEVERITY OF MAJOR DEPRESSIVE DISORDER* YONG-JUN WANG Tianjin AnDing Hospital, Capital Medical University, Beijing, and Tsinghua Univeristy, Beijing YU-TAO YANG HUI LI Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University PO-ZI LIU Tsinghua University, Beijing CHUAN-YUE WANG Beijing Key Laboratory of Mental Disorders, Capital Medical University ZHI-QING DAVID XU Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University
ABSTRACT
Objective: This study investigated the association between plasma galanin level and depression severity. Methods: The severity of depression symptoms of 79 patients with major depressive disorder (MDD; 52 women and 27 men, 71 patients in onset, 8 in remission) was assessed using the 17-item Hamilton
*This study was supported by the Beijing Municipal Natural Science Foundation of China (ID: 09G0013), Tianjin Health Bureau Technology Fund (ID: 2012KR01, 12KG111), and National Natural Science Foundation of China (ID: 81071083, 31271154, 31171032), Nerve Regeneration and Repair, Beijing Key Laboratory topics (ID: 2012SJZS04), Beijing Center for Neural Regeneration and Repairing (ID: 2012SJZS04), and The National Research Program of China 973 Program (2010CB912003). 109 Ó 2014, Baywood Publishing Co., Inc. doi: http://dx.doi.org/10.2190/PM.48.2.d http://baywood.com
110 / WANG ET AL.
Depression Rating Scale. Venous fasting blood samples (5 mL) were taken from the 79 MDD patients, 35 healthy siblings, and 19 healthy controls, and plasma samples were prepared. Galanin levels in the plasma were measured by radioimmunoassay. Results: Plasma galanin in MDD patients was significantly higher than that of remission patients, healthy siblings, or healthy controls (P < 0.05) There was no significant difference between the healthy sibling and healthy control groups (P = 0.924). Plasma galanin of remission patients was also significantly higher than that of healthy controls (P < 0.05). There was no significant correlation between age and galanin levels in the 79 patients (r = 0.053, P = 0.646), nor was there a correlation between age and galanin levels when patients were stratified by gender (P > 0.05). There was a significant positive correlation between plasma galanin levels and depression severity in women MDD patients (r = 0.329, df = 42, P = 0.020), but not in men patients. Conclusions: Plasma galanin levels may be an important biomarker for depression severity, especially in female patients. (Int’l. J. Psychiatry in Medicine 2014;48:109-119)
Key Words: major depressive disorder, Hamilton Depression Rating Scale, galanin, plasma
INTRODUCTION Major depressive disorder (MDD) is a severe disabling chronic disease that affects the lives of millions worldwide [1]. It is characterized by low mood, lack of enjoyment, pessimistic thinking, and reduced energy [2]. Substantial evidence has implicated dysfunction of brain serotonin (5-hydroxytryptamine [5-HT]) and noradrenaline neurons in the etiology of MDD, but the underlying mechanisms remain unclear [3]. The neuropeptide galanin is widely distributed in the central nervous system and peripheral tissues, and participates in a variety of physiological and pathological processes [4]. In particular, galanin functions to regulate brain 5-HT and noradrenaline in depression [5]. Preclinical data has indicated that galanin is involved in the pathogenesis of MDD [6, 7]. Galanin receptor agonists such as galmic and galnon produce an antidepressant-like effect in the rat [8]. M40 (galanin[1-13]-Pro-Pro[Ala-Leu]2-Ala amide), a galanin receptor antagonist, could act against the antidepressant-like effect of fluoxetine [9]. In a human study, intravenous administration of galanin had fast antidepressant efficacy and affected the sleep electroencephalogram [10]. Polymorphism of the galanin gene was found to be associated with symptom severity in female patients suffering from MDD [11]. However, whether the level of plasma galanin is associated with MDD has not been investigated. In this study, we compared the plasma galanin levels of patients with MDD and healthy controls, and investigated the association between plasma galanin levels and the severity of depression symptoms in men and women MDD patients.
GALANIN AS A MARKER OF MDD SEVERITY /
111
METHODS Study Setting and Subjects This study was conducted at Beijing AnDing Hospital, Capital Medical University, Beijing, between March and October 2009. Outpatients were screened via psychiatric interviews by an experienced researcher in accordance with the guidelines of the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; American Psychiatric Association, 1994). MDD Subjects were eligible if they were not suffering from a major neurological or medical illness. Seventy-nine patients with current MDD were recruited, 52 women (age, 37.8 ± 12.7 years) and 27 men (age, 32.1 ± 10.7 years; Table 1). In addition, the study included 35 healthy siblings of outpatient MDD patients, and 19 healthy controls (employees of the hospital). All subjects were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D). Remission in MDD patients was defined as an HAM-D score of less than 8. The Ethics Committee of Beijing AnDing Hospital, Capital Medical University, approved this study. All subjects signed written informed consent forms before the study. Radioimmunoassay Venous fasting blood samples (5 mL) were collected from the subjects between 8:00 a.m. and 9:00 a.m. directly into evacuated tubes containing ethylenediamine tetraacetic acid. The blood samples were immediately centrifuged at 3,000 rpm for 10 min. Galanin levels in the plasma were detected by radioimmunoassay using a kit (Phoenix Pharmaceuticals, CA) in accordance with the manufacturer’s
Table 1. Demographic Features, HAM-D Scores, HAMA Scores, and Galanin Plasma Levels of MDD Patients
Age (years) Body mass index (kg/m2) Age of onset (years) Galanin (ng/mL) HAM-D HAMA
Men (n = 27)
Women (n = 52)
32.1 ± 10.7 22.4 ± 3.6 27.8 ± 9.6 30.7 ± 8.3 19.5 ± 6.8 17.2 ± 11.8
37.8 ± 12.7 22.6 ± 2.8 31.3 ± 10.1 29.7 ± 7.8 17.8 ± 7.4 15.1 ± 8.4
t = –0.773, P = 0.444 t = 0.259, P = 0.797 t = –1.137, P = 0.262 t = 0.085, P = 0.933 t = 0.999, P = 0.321 t = –0.698, P = 0.489
Note: Data were expressed as mean ± standard deviation; HAM-D, the Hamilton Depression Rating Scale; HAMA, the Hamilton Anxiety Rating Scale.
112 / WANG ET AL.
instructions. The results were analyzed with the SN-695 gamma counter radioimmunoassay program, version 6.0. Statistical analysis Data were analyzed using SPSS version 16 statistical analysis software (SPSS, Chicago, IL). The independent-samples t-test and one-way ANOVA were performed to analyze the differences in galanin plasma levels among MDD patients, healthy siblings, and healthy controls. A P-value of < 0.05 was considered statistically significant. RESULTS Seventy-nine patients with MDD were enrolled in this study, including 52 women and 27 men (Table 1). There were no significant differences in age, age at MDD onset, body mass index, HAM-D score, Hamilton Anxiety Rating Scale (HAMA) score, or plasma galanin levels between men and women patients with MDD. There was a significant difference in plasma galanin among MDD patients, healthy siblings, and healthy controls (F = 34.152, P < 0.001; Table 2). Plasma galanin was higher in episode MDD than in remission, and patients in remission had significantly higher galanin levels than healthy controls (F = 37.372, P < 0.001; Table 3). Table 2. Differences in Plasma Galanin Concentration among MDD Patients, Healthy Siblings, and Healthy Controls
MDD Healthy siblings Healthy controls
n
Galanin (ng/ml)
F
P
79 35 19
31.20 ±10.61a 19.01 ± 1.00b 19.24 ± 2.07
34.152
