Neuroscience Research 83 (2014) 8–12
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Neuroscience Research journal homepage: www.elsevier.com/locate/neures
Serum neuropeptide Y in accident survivors with depression or posttraumatic stress disorder Daisuke Nishi a,b,c , Kenji Hashimoto d , Hiroko Noguchi b,e , Yutaka Matsuoka a,b,e,∗ a
Department of Psychiatry, National Disaster Medical Center, 3256 Midoricho, Tachikawa 190-0014, Japan CREST, Japan Science and Technology Agency, 3256 Midoricho, Tachikawa 190-0014, Japan Department of Mental Health Policy and Evaluation, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira 187-8551, Japan d Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan e Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira 187-8551, Japan b c
a r t i c l e
i n f o
Article history: Received 31 January 2014 Received in revised form 26 March 2014 Accepted 27 March 2014 Available online 4 April 2014 Keywords: Neuropeptide Y Depression PTSD Resilience
a b s t r a c t Although neuropeptide Y (NPY) has received attention for its potential anti-depressive and anti-anxiety effect, evidence in humans has been limited. This study aimed to clarify the relationships between serum NPY and depressive disorders, and posttraumatic stress disorder (PTSD) in accident survivors. Depressive disorders and PTSD were diagnosed by structural interviews at 1-month follow-up, and serum NPY was measured at the first assessment and 1-month follow-up. Analysis of variance was used to investigate significance of the differences identified. Furthermore, resilience was measured by self-report questionnaires. Multiple linear regression analyses were used to examine the relationship between resilience and serum NPY. Three hundred accident survivors participated in the assessment at the first assessment, and 138 completed the assessment at 1-month follow-up. Twenty-six participants had major depressive disorder and 6 had minor depressive disorder. Nine participants had PTSD and 16 had partial PTSD. No relationship existed between serum NPY and depressive disorders, PTSD, and resilience. The results of cannot be compared with those of NPY in the central nervous system (CNS), but these findings might be due to the nature of depression and PTSD in accident survivors. Further studies are needed to examine the relationships between NPY in CNS and depression and PTSD. © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
1. Introduction Neuropeptide Y (NPY) is a 36-amino acid peptide (Tatemoto et al., 1982) that is widely distributed in the central nervous system (CNS). NPY effects are mediated through at least four G proteincoupled receptors known as Y1 , Y2 , Y4 , and Y5 (Dumont et al., 1998). Among these receptors, Y1 and Y2 are mainly distributed in the frontal cortex, hippocampus, and amygdala (Dumont et al., 1998). There is growing interest in the possibility of NPY as a protective factor for depression and posttraumatic stress disorder (PTSD). Animal studies have shown that activation of Y1 receptors as well as deletion or blockade of Y2 receptors showed antidepressant-like activity (Heilig et al., 1989; Bannon et al., 2000; Redrobe et al.,
∗ Corresponding author at: Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan. Tel.: +81 42 346 3524; fax: +81 42 346 3557. E-mail address: [email protected] (Y. Matsuoka).
2002). Moreover, recent studies have suggested that Y4 and Y5 are also related to depression-like behaviors in rodents (Sorensen et al., 2004; Painsipp et al., 2008). Also, a recent review (Sah and Geracioti, 2013) suggested that NPY has an effect on PTSD given that NPY might have an anti-anxiety function (Heilig et al., 1993), regulate fear conditioning and extinction (Karlsson et al., 2005; Gutman et al., 2008; Fendt et al., 2009), and suppress startle responses and autonomic reactivity (Karl et al., 2010a,b). Some researchers have anticipated that enhancing NPY function might boost resilience or have an antidepressant effect (Southwick and Charney, 2012). However, evidence in humans shows some inconsistency. Patients with depression were found to have lower plasma NPY levels than controls (Hashimoto et al., 1996) and patients who had repeatedly attempted suicide showed low levels (Westrin et al., 1999), although no significant correlation with NPY-like immunoreactivity in cerebrospinal fluid (CSF) between depressed patients and controls was found in another study (Gjerris et al., 1992). Also, some studies reported lowered levels of NPY in plasma or CSF in PTSD patients (Rasmusson et al., 2000; Sah et al., 2009),
http://dx.doi.org/10.1016/j.neures.2014.03.009 0168-0102/© 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
D. Nishi et al. / Neuroscience Research 83 (2014) 8–12
whereas others reported that trauma exposure, not PTSD, was related to lowered plasma NPY in combat veterans (Morgan et al., 2003; Yehuda et al., 2006). Also, plasma NPY was shown to be negatively associated with psychological distress in the acute phase after trauma (Morgan et al., 2002) and was suggested to be a marker for resilience (Yehuda et al., 2006). This study aimed to clarify the relationships between serum NPY and resilience, major depression, and PTSD in accident survivors. We performed secondary analysis of the data acquired by the Tachikawa Cohort of Motor Vehicle Accidents (TCOM) Study (Matsuoka et al., 2009). 2. Methods 2.1. Participants We used the TCOM Study database (Matsuoka et al., 2009) following approval by the Research Ethics Committee of the National Disaster Medical Center (NDMC), Japan. Cohort inclusion criteria were (1) motor vehicle accident (MVA)-related severe physical injury causing a life-threatening or critical condition, (2) consecutive admittance to the emergency intensive care unit (ICU), (3) age 18–69 years, and (4) native Japanese speaker. Exclusion criteria were (1) diffuse axonal injury, brain contusion, or subdural or subarachnoid bleeding detected by computed tomography and/or magnetic resonance imaging; (2) cognitive impairment defined as a score of
Contents lists available at ScienceDirect
Neuroscience Research journal homepage: www.elsevier.com/locate/neures
Serum neuropeptide Y in accident survivors with depression or posttraumatic stress disorder Daisuke Nishi a,b,c , Kenji Hashimoto d , Hiroko Noguchi b,e , Yutaka Matsuoka a,b,e,∗ a
Department of Psychiatry, National Disaster Medical Center, 3256 Midoricho, Tachikawa 190-0014, Japan CREST, Japan Science and Technology Agency, 3256 Midoricho, Tachikawa 190-0014, Japan Department of Mental Health Policy and Evaluation, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira 187-8551, Japan d Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan e Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira 187-8551, Japan b c
a r t i c l e
i n f o
Article history: Received 31 January 2014 Received in revised form 26 March 2014 Accepted 27 March 2014 Available online 4 April 2014 Keywords: Neuropeptide Y Depression PTSD Resilience
a b s t r a c t Although neuropeptide Y (NPY) has received attention for its potential anti-depressive and anti-anxiety effect, evidence in humans has been limited. This study aimed to clarify the relationships between serum NPY and depressive disorders, and posttraumatic stress disorder (PTSD) in accident survivors. Depressive disorders and PTSD were diagnosed by structural interviews at 1-month follow-up, and serum NPY was measured at the first assessment and 1-month follow-up. Analysis of variance was used to investigate significance of the differences identified. Furthermore, resilience was measured by self-report questionnaires. Multiple linear regression analyses were used to examine the relationship between resilience and serum NPY. Three hundred accident survivors participated in the assessment at the first assessment, and 138 completed the assessment at 1-month follow-up. Twenty-six participants had major depressive disorder and 6 had minor depressive disorder. Nine participants had PTSD and 16 had partial PTSD. No relationship existed between serum NPY and depressive disorders, PTSD, and resilience. The results of cannot be compared with those of NPY in the central nervous system (CNS), but these findings might be due to the nature of depression and PTSD in accident survivors. Further studies are needed to examine the relationships between NPY in CNS and depression and PTSD. © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
1. Introduction Neuropeptide Y (NPY) is a 36-amino acid peptide (Tatemoto et al., 1982) that is widely distributed in the central nervous system (CNS). NPY effects are mediated through at least four G proteincoupled receptors known as Y1 , Y2 , Y4 , and Y5 (Dumont et al., 1998). Among these receptors, Y1 and Y2 are mainly distributed in the frontal cortex, hippocampus, and amygdala (Dumont et al., 1998). There is growing interest in the possibility of NPY as a protective factor for depression and posttraumatic stress disorder (PTSD). Animal studies have shown that activation of Y1 receptors as well as deletion or blockade of Y2 receptors showed antidepressant-like activity (Heilig et al., 1989; Bannon et al., 2000; Redrobe et al.,
∗ Corresponding author at: Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan. Tel.: +81 42 346 3524; fax: +81 42 346 3557. E-mail address: [email protected] (Y. Matsuoka).
2002). Moreover, recent studies have suggested that Y4 and Y5 are also related to depression-like behaviors in rodents (Sorensen et al., 2004; Painsipp et al., 2008). Also, a recent review (Sah and Geracioti, 2013) suggested that NPY has an effect on PTSD given that NPY might have an anti-anxiety function (Heilig et al., 1993), regulate fear conditioning and extinction (Karlsson et al., 2005; Gutman et al., 2008; Fendt et al., 2009), and suppress startle responses and autonomic reactivity (Karl et al., 2010a,b). Some researchers have anticipated that enhancing NPY function might boost resilience or have an antidepressant effect (Southwick and Charney, 2012). However, evidence in humans shows some inconsistency. Patients with depression were found to have lower plasma NPY levels than controls (Hashimoto et al., 1996) and patients who had repeatedly attempted suicide showed low levels (Westrin et al., 1999), although no significant correlation with NPY-like immunoreactivity in cerebrospinal fluid (CSF) between depressed patients and controls was found in another study (Gjerris et al., 1992). Also, some studies reported lowered levels of NPY in plasma or CSF in PTSD patients (Rasmusson et al., 2000; Sah et al., 2009),
http://dx.doi.org/10.1016/j.neures.2014.03.009 0168-0102/© 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
D. Nishi et al. / Neuroscience Research 83 (2014) 8–12
whereas others reported that trauma exposure, not PTSD, was related to lowered plasma NPY in combat veterans (Morgan et al., 2003; Yehuda et al., 2006). Also, plasma NPY was shown to be negatively associated with psychological distress in the acute phase after trauma (Morgan et al., 2002) and was suggested to be a marker for resilience (Yehuda et al., 2006). This study aimed to clarify the relationships between serum NPY and resilience, major depression, and PTSD in accident survivors. We performed secondary analysis of the data acquired by the Tachikawa Cohort of Motor Vehicle Accidents (TCOM) Study (Matsuoka et al., 2009). 2. Methods 2.1. Participants We used the TCOM Study database (Matsuoka et al., 2009) following approval by the Research Ethics Committee of the National Disaster Medical Center (NDMC), Japan. Cohort inclusion criteria were (1) motor vehicle accident (MVA)-related severe physical injury causing a life-threatening or critical condition, (2) consecutive admittance to the emergency intensive care unit (ICU), (3) age 18–69 years, and (4) native Japanese speaker. Exclusion criteria were (1) diffuse axonal injury, brain contusion, or subdural or subarachnoid bleeding detected by computed tomography and/or magnetic resonance imaging; (2) cognitive impairment defined as a score of
