title: Koukopoulos׳ diagnostic criteria for mixed depression: a validation study.
abstract: BACKGROUND
  Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos׳ proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study validates Koukopoulos׳ criteria as diagnostic for MxD.
  
  
  METHODS
  A sample of 435 patients from the International Mood Network (IMN), multi-center, international network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos׳ criteria were assessed in all patients.
  
  
  RESULTS
  The most prevalent MxD criteria were "absence of psychomotor retardation" (84%), "mood lability or marked reactivity" (78%), and "psychic agitation or inner tension" (75%). Multivariable predictors of a MxD (+) diagnosis were: higher current CGI (OR=1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR=0.54, 95% CI -3.28, -0.13), mixed symptoms on the index episode (OR=10.02, 95% CI 2.32, 24.12), rapid cycling course (OR=2.6 95% CI 1.45, 3.56), past substance abuse (OR=3.02, 95% CI 2.01, 5.67) and lower education status (OR=0.44, 95% CI -3.23, -0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%.
  
  
  CONCLUSIONS
  An external validation of these criteria in an independent sample is warranted.
  
  
  CONCLUSIONS
  A broad definition of mixed depression was internally validated with multiple diagnostic validators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos׳ broad criteria include agitation, irritability and mood lability as core features.
authors.affiliation: NESMOS Department (Neuroscience, Mental Health, and Sensory Organs), Sapienza University, School of Medicine and Psychology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy; Centro LucioBini, Rome, Italy; IRCCS Santa Lucia Foundation, Department of Clinical and Behavioral Neurology, Neuropsychiatry Laboratory, Rome, Italy. Electronic address: gabriele.sani@uniroma1.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sani
authors.affiliation: Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, USA; Departamento Psiquiatria Hospital Clinico, Facultad de Medicina, Universidad Chile, Santiago, Chile.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Vöhringer
authors.affiliation: NESMOS Department (Neuroscience, Mental Health, and Sensory Organs), Sapienza University, School of Medicine and Psychology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy; Centro LucioBini, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Napoletano
authors.affiliation: Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, USA.
authors.forename: Niki S
authors.initials: NS
authors.lastname: Holtzman
authors.affiliation: Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Dalley
authors.affiliation: NESMOS Department (Neuroscience, Mental Health, and Sensory Organs), Sapienza University, School of Medicine and Psychology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy; Centro LucioBini, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.affiliation: Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, USA; Tufts University School of Medicine, Boston, MA, USA.
authors.forename: S Nassir
authors.initials: SN
authors.lastname: Ghaemi
authors.affiliation: Centro LucioBini, Rome, Italy.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Koukopoulos
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000523:psychology; D005260:Female; D006801:Humans; D007508:Irritable Mood; D008297:Male; D008875:Middle Aged; D008960:Models, Psychological; D012372:ROC Curve
keywords: DSM-5; Diagnostic criteria; Excitatory symptoms; Mixed depression; Mood disorders