The acute phase response in panic disorder
A R T IC L E
International Journal of Neuropsychopharmacology (2005), 8, 529–535. Copyright f 2005 CINP doi:10.1017/S1461145705005432
Andre´s Herra´n1, Deirdre Sierra-Biddle1, Maria Teresa Garcı´a-Unzueta2, Jesu´s Puente3, Jose´ Luis Va´zquez-Barquero1 and Jose´ Antonio Amado2 Departments of 1 Psychiatry, 2 Endocrinology, and 3 Biochemistry, University of Cantabria, University Hospital Marque´s de Valdecilla, Santander, Spain
Abstract An acute-phase response (APR), manifested as an increase of acute-phase proteins has been shown in major depression. Panic disorder (PD) may share some aetiopathogenic mechanisms with depression, but APR has not been studied in this disorder. Forty-one panic patients in the first stages of their illness were compared with 32 healthy subjects of comparable sex, age, and body mass index. Clinical diagnosis was established with the Mini International Neuropsychiatric Interview, and severity with the Panic Disorder Severity Scale and the CGI scale. Laboratory determinations included four acute phase proteins (APPs) [albumin, gammaglobulins, fibrinogen, C-reactive-protein (CRP)] and basal cortisol level. Patients were studied after 8-wk follow-up taking selective serotonin reuptake inhibitors (SSRIs) to assess the evolution of the APPs. Gammaglobulin levels were lower, and both cortisol and CRP levels were higher in PD patients than in controls. APP did not differ between patients with or without agoraphobia. At follow-up, patients who responded to SSRIs presented a decrease in albumin levels, and a trend towards a decrease in cortisol and CRP compared with levels at intake. The conclusions of this study are that there is an APR in patients suffering from PD, and this APR tends to diminish after a successful treatment with SSRIs. Received 25 July 2004 ; Reviewed 26 December 2004 ; Revised 10 January 2005 ; Accepted 16 January 2005 Key words : Anxiety disorders, acute-phase proteins, acute-phase response, hypothalamo-hypophyseal system, panic disorder, serotonin uptake inhibitors.
Introduction The acute-phase response (APR) is a physiological sequence of events following different conditions. This response includes changes in plasma proteins, the so-called acute-phase proteins (APPs), and a number of other acute-phase phenomena (including fever, neuroendocrine changes, haematopoietic, metabolic and hepatic changes). It is supposed to be mediated mainly by interleukin-6 (IL-6), but also by the glucocorticoids and other cytokines, such as IL-10 and tumour necrosis factor. The APPs have been defined as those whose concentration increases by 25 % or more following inflammation (the positive APPs), although, some proteins show a decrease in their concentration during the course of the APR (the
Address for correspondence : Dr A. Herra´n, Department of Psychiatry, University Hospital Marque´s de Valdecilla, Avda. de Valdecilla s/n, 39008, Santander, Spain. Tel. : +34 942-202545 Fax : +34 942-203447 E-mail :
[email protected] Preliminary data of this work were presented as a communication at the European Certificate in Mood and Anxiety Disorders, Canterbury, Kent, UK, 2002.
negative APPs) (Whicher, 1990). As the APPs can be directly measured in plasma, they have been used as an evaluation of the activation of the inflammatory response system. The APR is associated with both acute and chronic inflammatory disorders, but also with medical and surgical conditions, and to a lesser degree, with psychological stress and mental disorders (Gabay and Kushner, 1999). For instance, in schizophrenia some authors have found an activation of the inflammatory response system (Lin et al., 1998 ; Maes et al., 1994). However, major depression has been the mental disorder most consistently related to this response. Several researchers have found increases in positive APPs and decreases in negative APPs, and this APR has been proposed as contributing to combined serotonin, inflammatory system, and hypothalamic– pituitary–adrenal (HPA) axis dysfunction in depression (Maes et al., 1993 ; van West and Maes, 1999). Major depression shows high rates of comorbidity with panic disorder (PD). Both illnesses also share some clinical features and respond to similar pharmacological treatments (Kessler, 2001 ; Weissman et al., 1997). These findings may indicate common
530
A. Herra´n et al.
aetiopathogenic mechanisms permitting speculation as to the contribution of the APR to PD, while controlling for depression APR in PD. However, APPs, as a reflection of the APR have not been evaluated in panic patients. Therefore, our aims have been to study the APPs as an expression of the APR in PD patients, and to evaluate their evolution after psychopharmacological treatment in a selected sample of panic patients during the first stages of their illness.
Subjects and methods Subjects We included consecutive patients from the clinical and research protocol of the Panic Disorder Unit of Cantabria (University Hospital Marque´s de Valdecilla, Santander, Spain). The aim of this programme is to include patients suffering from PD of recent onset. For this, subjects with a suspicion of presenting panic attacks, and seeking treatment for the first time, were referred from Mental Health Units and from the Emergency Department of the corresponding University Hospital. Then, a psychiatrist specializing in the field of anxiety disorders evaluated the patients in order to exclude previous psychological or psychopharmacological treatments for PD or agoraphobia (only subjects on doses of benzodiazepines less than or equal to the equivalent of 5 mg/d diazepam were admitted). Diagnosis was confirmed after the administration of the Mini International Neuropsychiatric Interview (MINI ; Sheehan et al., 1998). After being informed of the aims of the protocol and giving their informed consent, patients entered a flexible-dose selective serotonin reuptake inhibitors (SSRIs) treatment programme (doses were raised as needed up to 50 mg/d paroxetine or equivalent). In addition to the SSRIs, low doses of benzodiazepines (up to 5 mg/d diazepam or equivalent) were admitted. After an 8-wk follow-up period, patients were evaluated to assess treatment response. Response was defined as having much or very much improvement in the CGI – Change scale, and having a Panic Disorder Severity Scale (PDSS) score at least 30 % below their baseline (Shear et al., 1998). Inclusion criteria for the present study included PD criteria with or without agoraphobia (DSM-IV ; APA, 1994), the absence of previous psychiatric treatment for panic–agoraphobia, and informed consent to enter in the study. Exclusion criteria included age
