Psychiatry Research 217 (2014) 198–201
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Serum albumin correlates with affective prosody in adult males with attention-deficit hyperactivity disorder Marco Grabemann a,n, Christian Mette a, Marco Zimmermann a, Jens Wiltfang b, Bernhard Kis b a LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Altendorfer Street 97-101, 45143 Essen, Germany b Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, von-Siebold-Street 5, 37075 Goettingen, Germany
art ic l e i nf o
a b s t r a c t
Article history: Received 16 September 2013 Received in revised form 3 February 2014 Accepted 24 March 2014 Available online 3 April 2014
The aim of this study was to determine the relationship between serum albumin, affective prosody, and symptoms of attention-deficit hyperactivity disorder (ADHD) found coincidentally in a recently published study. Here, serum albumin levels were assessed as a covariate. Twenty healthy male adults (controls) and 20 adult male patients with ADHD participated in the study on two study days. Serum albumin levels and performance in an affective prosody task were assessed, and correlations were determined. Serum albumin had a significant correlation with performance on an affective prosody task on both of the 2 study days. The same correlations were not significant in the healthy control group. There was no difference in the serum albumin level between patients with ADHD and healthy controls. The association between serum albumin and affective prosody in adults with ADHD is a novel finding. However, to date, there is no clear theory that explains this association. Future research should analyze whether serum albumin influences causes changes in performance in affective prosody using experimental designs. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Attention-deficit disorder with hyperactivity Serum albumin Phonetics
1. Introduction In a study concerning the impact of the acute tryptophan depletion (ATD) procedure, which reduces central nervous system serotonin, on affective prosody in adult male patients with attention-deficit hyperactivity disorder (Grabemann et al., 2013), we found an additional result that we wish to report and discuss here. Hyperactivity, impulsivity, and inattention are the core symptoms of attention-deficit hyperactivity disorder (ADHD). The aim of our primary study was to determine whether affective prosody is impaired in adult patients with ADHD as compared with healthy adults and the contribution of central nervous system serotonin (CNS) to these variables. Affective prosody consists of the emotional tone of language, e.g., happiness, sadness, fear, and anger. It is a component of general prosody, which further includes linguistic, dialectical, and idiosyncratic components (Uekermann et al., 2010). In that study (Grabemann et al., 2013; see Mette et al., 2013; Zimmermann et al., 2012), the authors demonstrated that the processing of affective prosody was impaired in patients with ADHD compared with healthy controls on two study days;
n
Corresponding author. Tel.: þ 49 201 7227 202; fax. þ 49 201 7227 303. E-mail address: [email protected] (M. Grabemann).
http://dx.doi.org/10.1016/j.psychres.2014.03.030 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
however, there was no effect of serotonin on this impairment (Grabemann et al., 2013). As a covariable, the serum albumin level was measured via electrophoresis. Serum albumin is a protein responsible for oncotic pressure and has important roles in transport and storage in the blood. Serum albumin stores and carries free fatty acids, hormones, amino acids, and active ingredients of drugs (Carlson, 2004). Consequently, we describe an association between serum albumin and affective prosody in adult patients with ADHD. Furthermore, we show that affective prosody does not correlate with other proteins in the blood serum (Leucin, Isoleucin, Biblirubin, Phenylalanin).
2. Methods 2.1. Study sample Twenty male patients diagnosed with ADHD (mean age ¼30.25 years, S. D. ¼9.38 years) based on DSM-IV criteria and 20 male healthy controls (mean age ¼27.90 years, S.D.¼ 6.02 years) participated in this study, which had a repeated measure design (two study days with a delay of one week). Patients were recruited from the ADHD outpatient clinic of the Department of Psychiatry and Psychotherapy of the University Duisburg-Essen, Germany. The control group was recruited from adjacent universities and hospitals. Potential participants diagnosed with asthma, obesity, diabetes, substance abuse, a psychotic disorder, or any
M. Grabemann et al. / Psychiatry Research 217 (2014) 198–201 neurological disease were excluded from the study. Further exclusion criteria for patients with ADHD included co-morbid depression, other mood disorders, or the use of methylphenidate (MPH) on the days the study was conducted. Patients using MPH were instructed to stop their medication 24 h prior to each study day, and these patients confirmed that they had followed these instructions. Both patients with ADHD and healthy controls were comparable with respect to age (t(32.4) ¼-0.94, p 40.05) and IQ (Wechsler Intelligence Scale t(38) ¼ 0.41, p 40.05). No participant had an IQ score below 85, which was a further exclusion criterion. Patients did show significantly higher scores than control subjects on both the Wender Utah Rating Scale (WURS; t(33.9) ¼ 6.1, p o 0.01) and the ADHD self-report scale (t(28.9) ¼28.88, p o 0.01). There were no significant differences between groups on the Barrat Impulsiveness Scale, although patients with ADHD achieved higher scores (t(38) ¼ 1.86, p 40.05). All participants provided verbal and written informed consent. The study was carried out in accordance with the guidelines of the Declaration of Helsinki (as revised in 1983). In addition, the Ethics Committee of the University of Duisburg-Essen assessed and approved the study.
2.2. Measure of serum albumin On both study days blood samples were collected by a physician. Levels of serum albumin were measured nephelometrically (MLM medical labs, Moenchengladbach, Germany).
2.3. Measure of affective prosody The “Tubingen Affect Battery” (Breitenstein et al., 1996) is a reliable and valid test that is used to assess the perception of affective prosody. The following subtests were used: 1) Naming the affective prosody of sentences with neutral semantic content.
In this subtest, participants heard 15 semantically neutral sentences. Their task was to identify the affective prosody of these sentences. The emotions displayed were “happiness,” “anger,” “fear,” “sadness,” and “neutral.”
199
3. Results On the first study day, we found a significant correlation between affective prosody and serum albumin in the group of patients with ADHD (r ¼0.57, p ¼0.009). The same correlation was not statistically significant in the control group (r ¼0.098, p ¼0.68). Fig. 1 shows the scatter plots for these correlations for both groups. We did not identify any outlier that could have caused the significant correlation in the group of patients with ADHD. In addition, the scatter plot seemed to be coherent in the group of patients with ADHD. According to the statistical analysis for the healthy control group, the scatter plot seemed to decay at the bottom and top. Therefore, homoscedasticity did not exist. On the second study day, we also found a significant correlation between serum albumin and performance in affective prosody (r ¼0.557, p ¼0.011). In addition, there was no significant correlation between these variables in the healthy control group (r ¼0.117, p¼ 0.622) (Fig. 2). The scatter plot of the group of patients with ADHD seems to be coherent, and there is no indication that an outlier causes the relationship between serum albumin and affective prosody on the second study day. In the healthy control group, the scatter plot seems to decay at the top and bottom. In this case, homoscedasticity did not exist. Furthermore, we analyzed whether serum albumin levels differ between group of patients with ADHD and the control group (Table 1). The t-tests did not reveal significant differences between the groups (study day 1: t(38) ¼1.098, p¼ 0.279; study day 2: t(38) ¼1.31, p ¼ 0.199). On both days the analyses of premises of parametrical testing conducted with Kolmogorov–Smirnov-Tests demonstrated that homoscedasticity and normal distribution of residua were given (day 1: K(40) ¼ 0.098, p 40.2, day 2: K(40) ¼0.11, po 0.2) Therefore, the use of t-tests were indicated.
2) Naming congruent and incongruent semantic prosody.
In this subtest, 32 sentences were presented. In 24 of the sentences, the semantic content did not match the affective prosody; in 8 sentences, both aspects were congruent. Participants were asked to name the affective content of the voice and to ignore the semantic content of the sentences. The emotions displayed were the same as those from task 2.
2.4. Data analysis Separate correlations were calculated between serum albumin and affective prosody for both groups (patients with ADHD and healthy controls) on both study days. A t-test was performed to determine whether serum albumin levels differed significantly between patients with ADHD and healthy controls. SPSS Version 21 (IBMs Armonk, New York) was used for data analysis.
4. Discussion The results from the present study demonstrate that serum albumin correlates with the processing of affective prosody only in adult male patients with ADHD, which is a novel finding. These associations were found on two separate study days. In this paragraph, we discuss the hypothesis that serum albumin contributes to impairments in processing affective prosody and influences the degree of this impairment which was described by Grabemann et al. (2013). In the field of ADHD there are no studies which report a similar association. Several studies have reported correlations between serum albumin and higher
Fig. 1. Scatter plots for both correlations on study day 1 (a: Patients with ADHD, and b: Healthy controls).
200
M. Grabemann et al. / Psychiatry Research 217 (2014) 198–201
Fig. 2. Scatter plots for both correlations on study day 2 (a: Patients with ADHD, and b: Healthy controls).
Table 1 Means and standard deviations of serum albumin for patients with ADHD and healthy controls for both study days. Group
Mean (g/l)
Standard deviation
Serum albumin level on study day 1
Patients with ADHD Healthy controls
47.99 48.80
2.89 1.58
Serum albumin level on study day 2
Patients with ADHD Healthy controls
46.90 47.98
2.93 2.25
cognitive functioning in individuals with other psychiatric conditions. Mizrahi et al. (2008) demonstrated that serum albumin correlates with performance on the mini-mental status examination (MMSE) in patients older than 65 years of age who suffer from hip fractures. The authors showed that patients with a low albumin level were at a greater risk of developing cognitive impairment in the future. In addition, Ng et al. (2008) demonstrated that low serum albumin is independently associated with cognitive decline in older adults. Llewellyn et al. (2010) estimated that the risk of developing cognitive impairment is 1.5–2.5-fold higher in older adults when the serum albumin level is low. Contrary to the evidence above, Dik et al. (2005) showed that in older adults, serum albumin is not associated with MMSE performance, Raven's colored progressive matrices, or an information processing speed task. Furthermore, some studies have stressed the importance of serum albumin in individuals with psychiatric disorders and emotional impairments. Huang (2002) and Huang et al. (2005) demonstrated that serum albumin levels were significantly reduced in patients with major depression compared with healthy controls. Furthermore, they found that the severity of major depression was negatively correlated with serum album level. Huang and Lee (2007) demonstrated that the serum albumin level was significantly lower in hemodialysis patients with major depression compared with hemodialysis patients without depression. The authors hypothesized that an inflammatory reaction and oxidative damage may be more severe in hemodialysis patients with major depression, although a distinct pathophysiological mechanism has not been proposed. To date, there is no specific theory regarding the mechanism by which serum albumin modulates the impairment of affective prosody processing noted in adult patients with ADHD. Huang (2002), Llewellyn et al. (2010), and Mizrahi et al. (2008) suggested
that inflammation is involved in cognitive decline of older people. They argue that serum albumin is considered to be a part of the acute-phase response of the immune system. This response involves a release of cytokines, an up-regulation of acute-phase proteins (e.g., c-reactive protein), and a down-regulation of anti-acute-phase proteins (e.g., serum albumin). Oades et al. (2010) investigated inflammation in the field of ADHD research. They have reported associations between cytokines and inattention as well as hyperactivity in children with ADHD. These results seem to indicate that inflammation is involved in the pathology of ADHD. However, the present results do not support the assumption that a reaction of the immune system causes the relationship between serum albumin and affective prosody in patients with ADHD. The serum albumin level did not differ significantly between the patient group and healthy controls on either study day. In the case of an involvement of inflammation, it is expected that the serum albumin level is lower in patients with ADHD compared with healthy controls. To our knowledge, the present study is the first to demonstrate that the serum albumin level is a predictor of affective prosody processing and that it may be involved in the pathophysiology of ADHD. Indeed, this is the first study to investigate serum albumin in adult patients with ADHD. Some limitations of this study should be considered. First, the sample size of the study was small; thus, a replication of the results using a larger sample is desirable. Second, only male participants participated in the study; therefore, further studies should rule out a gender effect on the relationship identified in this study. Third, the present results were not replicated in an experimental study that was designed to test the influence of serum albumin on affective prosody or on symptoms of ADHD. Thus, further studies should seek to manipulate serum albumin concentration in patients. Such an experimental design would be appropriate for drawing conclusions whether serum albumin influences the processing of affective prosody or has an impact on the degree of ADHD symptoms.
Funding and disclosure Dr. Bernhard Kis received speaker honoraria from and serves as an advisory board member for Medice and Servier, in addition to being an advisory board member for Novartis. M.Sc. Christian Mette received speaker honoraria from Medice. M.Sc. Marco Grabemann, M.Sc. Marco Zimmermann and Prof. Dr. Jens Wiltfang declare no potential conflict of interest.
M. Grabemann et al. / Psychiatry Research 217 (2014) 198–201
Acknowledgments We are grateful to Junior Professor Florian Daniel Zepf, MD for his scientific support and generous advice. References Breitenstein, C., Daum, I., Ackermann, H., Lütgehetmann, R, Müller, E., 1996. Erfassung der Emotionswahrnehmung bei zentralnervö sen Läsionen und Erkrankungen: Psychometrische Gütekriterien der "Tübinger Affekt Batterie". Neurologie und Rehabilitation 2, 93–101. Carlson, N.R., 2004. Physiologische Psychologie, 8th ed. Pearson Studium, München. Dik, M.G., Jonker, C., Hack, C.E., Smit, J.H., Comijs, H.C., Eikelenboom, P., 2005. Serum inflammatory proteins and cognitive decline in older persons. Neurology 64, 1371–1377. Grabemann, M., Mette, C., Zimmermann, M., Heinrich, V., Uekermann, J., Wiltfang, J., Abdel-Hamid, M., Zepf, F.D., Kis, B., 2013. No effects of acute tryptophan depletion on processing affective prosody in male adults with ADHD. Acta Psychiatrica Scandinavica 128, 142–148. Huang, S., Chiu, C., Shen, W.W., Chang, H., Wu, P., Su, K., 2005. Hypoalbuminemia in drug-free patients with major depressive disorder compared with a dietary matched control group: a clinical meaning beyond malnutrition. European Neuropsychopharmacology 15, 227–230. Huang, T., 2002. Lower serum albumin levels in patients with mood disorders. Chang Gung Medicine Journal 25, 509–513.
201
Huang, T., Lee, C., 2007. Low serum albumin and high ferritin levels in chronic hemodialysis patients with major depression. Psychiatry Research 152, 277–280. Llewellyn, D.J., Langa, K.M., Friedland, R.P., Lang, I.A., 2010. Serum albumin concentration and cognitive impairment. Current Alzheimer Research 7, 91–96. Mette, C., Zimmermann, M., Grabemann, M., Abdel-Hamid, M., Uekermann, J., Biskup, C.S., Wiltfang, J., Zepf, D., Kis, B., 2013. The impact of acute tryptophan depletion on attentional performance in adult patients with ADHD. Acta Psychiatrica Scandinavica 128, 124–132. Mizrahi, E.H., Blumstein, T., Arad, M., Adunsky, A., 2008. Serum albumin levels predict cognitive impairment in elderly hip fracture patients. American Journal of Alzheimer’s Disease and Other Dementias 23, 85–90. Ng, T., Feng, L., Niti, M., Yap, K.B., 2008. Albumin, haemoglobin, BMI and cognitive performance in older adults. Age and Ageing 37, 423–429. Oades, R.D., Myint, A., Dauvermann, M.R., Schimmelmann, B.G., Schwarz, M.J., 2010. Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention. Behavioral and Brain Functions 6, 32. Uekermann, J., Kraemer, M., Abdel-Hamid, M., Schimmelmann, B.G., Hebebrand, J., Daum, I., Wiltgfang, J., Kis, B., 2010. Social cognition in attention-deficit hyperactivity disorder (ADHD). Neuroscience and Biobehavioral Reviews 34, 734–743. Zimmermann, M., Grabemann, M., Mette, C., Abdel-Hamid, M., Uekermann, J., Kraemer, M., Wiltfang, J., Kis, B., Zepf, F.D., 2012. The effects of acute tryptophan depletion on reactive aggression in adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls. PLoS ONE 7, e32023, http://dx.doi.org/ 10.1371/journal.pone.0032023.
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Serum albumin correlates with affective prosody in adult males with attention-deficit hyperactivity disorder Marco Grabemann a,n, Christian Mette a, Marco Zimmermann a, Jens Wiltfang b, Bernhard Kis b a LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Altendorfer Street 97-101, 45143 Essen, Germany b Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, von-Siebold-Street 5, 37075 Goettingen, Germany
art ic l e i nf o
a b s t r a c t
Article history: Received 16 September 2013 Received in revised form 3 February 2014 Accepted 24 March 2014 Available online 3 April 2014
The aim of this study was to determine the relationship between serum albumin, affective prosody, and symptoms of attention-deficit hyperactivity disorder (ADHD) found coincidentally in a recently published study. Here, serum albumin levels were assessed as a covariate. Twenty healthy male adults (controls) and 20 adult male patients with ADHD participated in the study on two study days. Serum albumin levels and performance in an affective prosody task were assessed, and correlations were determined. Serum albumin had a significant correlation with performance on an affective prosody task on both of the 2 study days. The same correlations were not significant in the healthy control group. There was no difference in the serum albumin level between patients with ADHD and healthy controls. The association between serum albumin and affective prosody in adults with ADHD is a novel finding. However, to date, there is no clear theory that explains this association. Future research should analyze whether serum albumin influences causes changes in performance in affective prosody using experimental designs. & 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Attention-deficit disorder with hyperactivity Serum albumin Phonetics
1. Introduction In a study concerning the impact of the acute tryptophan depletion (ATD) procedure, which reduces central nervous system serotonin, on affective prosody in adult male patients with attention-deficit hyperactivity disorder (Grabemann et al., 2013), we found an additional result that we wish to report and discuss here. Hyperactivity, impulsivity, and inattention are the core symptoms of attention-deficit hyperactivity disorder (ADHD). The aim of our primary study was to determine whether affective prosody is impaired in adult patients with ADHD as compared with healthy adults and the contribution of central nervous system serotonin (CNS) to these variables. Affective prosody consists of the emotional tone of language, e.g., happiness, sadness, fear, and anger. It is a component of general prosody, which further includes linguistic, dialectical, and idiosyncratic components (Uekermann et al., 2010). In that study (Grabemann et al., 2013; see Mette et al., 2013; Zimmermann et al., 2012), the authors demonstrated that the processing of affective prosody was impaired in patients with ADHD compared with healthy controls on two study days;
n
Corresponding author. Tel.: þ 49 201 7227 202; fax. þ 49 201 7227 303. E-mail address: [email protected] (M. Grabemann).
http://dx.doi.org/10.1016/j.psychres.2014.03.030 0165-1781/& 2014 Elsevier Ireland Ltd. All rights reserved.
however, there was no effect of serotonin on this impairment (Grabemann et al., 2013). As a covariable, the serum albumin level was measured via electrophoresis. Serum albumin is a protein responsible for oncotic pressure and has important roles in transport and storage in the blood. Serum albumin stores and carries free fatty acids, hormones, amino acids, and active ingredients of drugs (Carlson, 2004). Consequently, we describe an association between serum albumin and affective prosody in adult patients with ADHD. Furthermore, we show that affective prosody does not correlate with other proteins in the blood serum (Leucin, Isoleucin, Biblirubin, Phenylalanin).
2. Methods 2.1. Study sample Twenty male patients diagnosed with ADHD (mean age ¼30.25 years, S. D. ¼9.38 years) based on DSM-IV criteria and 20 male healthy controls (mean age ¼27.90 years, S.D.¼ 6.02 years) participated in this study, which had a repeated measure design (two study days with a delay of one week). Patients were recruited from the ADHD outpatient clinic of the Department of Psychiatry and Psychotherapy of the University Duisburg-Essen, Germany. The control group was recruited from adjacent universities and hospitals. Potential participants diagnosed with asthma, obesity, diabetes, substance abuse, a psychotic disorder, or any
M. Grabemann et al. / Psychiatry Research 217 (2014) 198–201 neurological disease were excluded from the study. Further exclusion criteria for patients with ADHD included co-morbid depression, other mood disorders, or the use of methylphenidate (MPH) on the days the study was conducted. Patients using MPH were instructed to stop their medication 24 h prior to each study day, and these patients confirmed that they had followed these instructions. Both patients with ADHD and healthy controls were comparable with respect to age (t(32.4) ¼-0.94, p 40.05) and IQ (Wechsler Intelligence Scale t(38) ¼ 0.41, p 40.05). No participant had an IQ score below 85, which was a further exclusion criterion. Patients did show significantly higher scores than control subjects on both the Wender Utah Rating Scale (WURS; t(33.9) ¼ 6.1, p o 0.01) and the ADHD self-report scale (t(28.9) ¼28.88, p o 0.01). There were no significant differences between groups on the Barrat Impulsiveness Scale, although patients with ADHD achieved higher scores (t(38) ¼ 1.86, p 40.05). All participants provided verbal and written informed consent. The study was carried out in accordance with the guidelines of the Declaration of Helsinki (as revised in 1983). In addition, the Ethics Committee of the University of Duisburg-Essen assessed and approved the study.
2.2. Measure of serum albumin On both study days blood samples were collected by a physician. Levels of serum albumin were measured nephelometrically (MLM medical labs, Moenchengladbach, Germany).
2.3. Measure of affective prosody The “Tubingen Affect Battery” (Breitenstein et al., 1996) is a reliable and valid test that is used to assess the perception of affective prosody. The following subtests were used: 1) Naming the affective prosody of sentences with neutral semantic content.
In this subtest, participants heard 15 semantically neutral sentences. Their task was to identify the affective prosody of these sentences. The emotions displayed were “happiness,” “anger,” “fear,” “sadness,” and “neutral.”
199
3. Results On the first study day, we found a significant correlation between affective prosody and serum albumin in the group of patients with ADHD (r ¼0.57, p ¼0.009). The same correlation was not statistically significant in the control group (r ¼0.098, p ¼0.68). Fig. 1 shows the scatter plots for these correlations for both groups. We did not identify any outlier that could have caused the significant correlation in the group of patients with ADHD. In addition, the scatter plot seemed to be coherent in the group of patients with ADHD. According to the statistical analysis for the healthy control group, the scatter plot seemed to decay at the bottom and top. Therefore, homoscedasticity did not exist. On the second study day, we also found a significant correlation between serum albumin and performance in affective prosody (r ¼0.557, p ¼0.011). In addition, there was no significant correlation between these variables in the healthy control group (r ¼0.117, p¼ 0.622) (Fig. 2). The scatter plot of the group of patients with ADHD seems to be coherent, and there is no indication that an outlier causes the relationship between serum albumin and affective prosody on the second study day. In the healthy control group, the scatter plot seems to decay at the top and bottom. In this case, homoscedasticity did not exist. Furthermore, we analyzed whether serum albumin levels differ between group of patients with ADHD and the control group (Table 1). The t-tests did not reveal significant differences between the groups (study day 1: t(38) ¼1.098, p¼ 0.279; study day 2: t(38) ¼1.31, p ¼ 0.199). On both days the analyses of premises of parametrical testing conducted with Kolmogorov–Smirnov-Tests demonstrated that homoscedasticity and normal distribution of residua were given (day 1: K(40) ¼ 0.098, p 40.2, day 2: K(40) ¼0.11, po 0.2) Therefore, the use of t-tests were indicated.
2) Naming congruent and incongruent semantic prosody.
In this subtest, 32 sentences were presented. In 24 of the sentences, the semantic content did not match the affective prosody; in 8 sentences, both aspects were congruent. Participants were asked to name the affective content of the voice and to ignore the semantic content of the sentences. The emotions displayed were the same as those from task 2.
2.4. Data analysis Separate correlations were calculated between serum albumin and affective prosody for both groups (patients with ADHD and healthy controls) on both study days. A t-test was performed to determine whether serum albumin levels differed significantly between patients with ADHD and healthy controls. SPSS Version 21 (IBMs Armonk, New York) was used for data analysis.
4. Discussion The results from the present study demonstrate that serum albumin correlates with the processing of affective prosody only in adult male patients with ADHD, which is a novel finding. These associations were found on two separate study days. In this paragraph, we discuss the hypothesis that serum albumin contributes to impairments in processing affective prosody and influences the degree of this impairment which was described by Grabemann et al. (2013). In the field of ADHD there are no studies which report a similar association. Several studies have reported correlations between serum albumin and higher
Fig. 1. Scatter plots for both correlations on study day 1 (a: Patients with ADHD, and b: Healthy controls).
200
M. Grabemann et al. / Psychiatry Research 217 (2014) 198–201
Fig. 2. Scatter plots for both correlations on study day 2 (a: Patients with ADHD, and b: Healthy controls).
Table 1 Means and standard deviations of serum albumin for patients with ADHD and healthy controls for both study days. Group
Mean (g/l)
Standard deviation
Serum albumin level on study day 1
Patients with ADHD Healthy controls
47.99 48.80
2.89 1.58
Serum albumin level on study day 2
Patients with ADHD Healthy controls
46.90 47.98
2.93 2.25
cognitive functioning in individuals with other psychiatric conditions. Mizrahi et al. (2008) demonstrated that serum albumin correlates with performance on the mini-mental status examination (MMSE) in patients older than 65 years of age who suffer from hip fractures. The authors showed that patients with a low albumin level were at a greater risk of developing cognitive impairment in the future. In addition, Ng et al. (2008) demonstrated that low serum albumin is independently associated with cognitive decline in older adults. Llewellyn et al. (2010) estimated that the risk of developing cognitive impairment is 1.5–2.5-fold higher in older adults when the serum albumin level is low. Contrary to the evidence above, Dik et al. (2005) showed that in older adults, serum albumin is not associated with MMSE performance, Raven's colored progressive matrices, or an information processing speed task. Furthermore, some studies have stressed the importance of serum albumin in individuals with psychiatric disorders and emotional impairments. Huang (2002) and Huang et al. (2005) demonstrated that serum albumin levels were significantly reduced in patients with major depression compared with healthy controls. Furthermore, they found that the severity of major depression was negatively correlated with serum album level. Huang and Lee (2007) demonstrated that the serum albumin level was significantly lower in hemodialysis patients with major depression compared with hemodialysis patients without depression. The authors hypothesized that an inflammatory reaction and oxidative damage may be more severe in hemodialysis patients with major depression, although a distinct pathophysiological mechanism has not been proposed. To date, there is no specific theory regarding the mechanism by which serum albumin modulates the impairment of affective prosody processing noted in adult patients with ADHD. Huang (2002), Llewellyn et al. (2010), and Mizrahi et al. (2008) suggested
that inflammation is involved in cognitive decline of older people. They argue that serum albumin is considered to be a part of the acute-phase response of the immune system. This response involves a release of cytokines, an up-regulation of acute-phase proteins (e.g., c-reactive protein), and a down-regulation of anti-acute-phase proteins (e.g., serum albumin). Oades et al. (2010) investigated inflammation in the field of ADHD research. They have reported associations between cytokines and inattention as well as hyperactivity in children with ADHD. These results seem to indicate that inflammation is involved in the pathology of ADHD. However, the present results do not support the assumption that a reaction of the immune system causes the relationship between serum albumin and affective prosody in patients with ADHD. The serum albumin level did not differ significantly between the patient group and healthy controls on either study day. In the case of an involvement of inflammation, it is expected that the serum albumin level is lower in patients with ADHD compared with healthy controls. To our knowledge, the present study is the first to demonstrate that the serum albumin level is a predictor of affective prosody processing and that it may be involved in the pathophysiology of ADHD. Indeed, this is the first study to investigate serum albumin in adult patients with ADHD. Some limitations of this study should be considered. First, the sample size of the study was small; thus, a replication of the results using a larger sample is desirable. Second, only male participants participated in the study; therefore, further studies should rule out a gender effect on the relationship identified in this study. Third, the present results were not replicated in an experimental study that was designed to test the influence of serum albumin on affective prosody or on symptoms of ADHD. Thus, further studies should seek to manipulate serum albumin concentration in patients. Such an experimental design would be appropriate for drawing conclusions whether serum albumin influences the processing of affective prosody or has an impact on the degree of ADHD symptoms.
Funding and disclosure Dr. Bernhard Kis received speaker honoraria from and serves as an advisory board member for Medice and Servier, in addition to being an advisory board member for Novartis. M.Sc. Christian Mette received speaker honoraria from Medice. M.Sc. Marco Grabemann, M.Sc. Marco Zimmermann and Prof. Dr. Jens Wiltfang declare no potential conflict of interest.
M. Grabemann et al. / Psychiatry Research 217 (2014) 198–201
Acknowledgments We are grateful to Junior Professor Florian Daniel Zepf, MD for his scientific support and generous advice. References Breitenstein, C., Daum, I., Ackermann, H., Lütgehetmann, R, Müller, E., 1996. Erfassung der Emotionswahrnehmung bei zentralnervö sen Läsionen und Erkrankungen: Psychometrische Gütekriterien der "Tübinger Affekt Batterie". Neurologie und Rehabilitation 2, 93–101. Carlson, N.R., 2004. Physiologische Psychologie, 8th ed. Pearson Studium, München. Dik, M.G., Jonker, C., Hack, C.E., Smit, J.H., Comijs, H.C., Eikelenboom, P., 2005. Serum inflammatory proteins and cognitive decline in older persons. Neurology 64, 1371–1377. Grabemann, M., Mette, C., Zimmermann, M., Heinrich, V., Uekermann, J., Wiltfang, J., Abdel-Hamid, M., Zepf, F.D., Kis, B., 2013. No effects of acute tryptophan depletion on processing affective prosody in male adults with ADHD. Acta Psychiatrica Scandinavica 128, 142–148. Huang, S., Chiu, C., Shen, W.W., Chang, H., Wu, P., Su, K., 2005. Hypoalbuminemia in drug-free patients with major depressive disorder compared with a dietary matched control group: a clinical meaning beyond malnutrition. European Neuropsychopharmacology 15, 227–230. Huang, T., 2002. Lower serum albumin levels in patients with mood disorders. Chang Gung Medicine Journal 25, 509–513.
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