title: Serum biomarkers predictive of depressive episodes in panic disorder.
abstract: Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA). We assessed the predictive performance of serum biomarkers, clinical, and self-report variables using receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC). False-discovery-rate corrected logistic regression model selection of serum analytes and covariates identified an optimal predictive panel comprised of tetranectin and creatine kinase MB along with patient gender and scores from the Inventory of Depressive Symptomatology (IDS) rating scale. Combined, an AUC of 0.87 was reached for identifying the PD/PDA patients who developed a depressive disorder within 2 years (n = 44). The addition of biomarkers represented a significant (p = 0.010) improvement over using gender and IDS alone as predictors (AUC = 0.78). For the first time, we report on a combination of biological serum markers, clinical variables and self-report inventories that can detect PD/PDA patients at increased risk of developing subsequent depressive disorders with good predictive performance in a naturalistic cohort design. After an independent validation our proposed biomarkers could prove useful in the detection of at-risk PD/PDA patients, allowing for early therapeutic interventions and improving clinical outcome.
authors.affiliation: Department of Chemical Engineering and Biotechnology, Cambridge Centre for Neuropsychiatric Research, University of Cambridge, Cambridge, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Gottschalk
authors.affiliation: Department of Chemical Engineering and Biotechnology, Cambridge Centre for Neuropsychiatric Research, University of Cambridge, Cambridge, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Department of Chemical Engineering and Biotechnology, Cambridge Centre for Neuropsychiatric Research, University of Cambridge, Cambridge, UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Chan
authors.affiliation: Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Bot
authors.affiliation: Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: b.penninx@vumc.nl.
authors.forename: B W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Chemical Engineering and Biotechnology, Cambridge Centre for Neuropsychiatric Research, University of Cambridge, Cambridge, UK. Electronic address: sb209@cam.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015331:Cohort Studies; D052279:Creatine Kinase, MB Form / Q000097:blood*; D003863:Depression / Q000097:blood* / Q000209:etiology*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000150:complications*; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D037181:Lectins, C-Type; C060820:fibulin; C048648:tetranectin; D052279:Creatine Kinase, MB Form
keywords: Major depressive episode; Panic disorder; Prediction; Prognosis; Risk factor; Secondary depression