title: Mixed Depression in Bipolar Disorder: Prevalence Rate and Clinical Correlates During Naturalistic Follow-Up in the Stanley Bipolar Network.
abstract: OBJECTIVE
  DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression.
  
  
  METHODS
  In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology-Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit.
  
  
  RESULTS
  Mixed depression, defined as an IDS-C score ≥15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring ≥3 nonoverlapping YMRS items concurrent with an IDS-C score ≥15, to broader definitions requiring ≥2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity.
  
  
  CONCLUSIONS
  Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Shefali
authors.initials: S
authors.lastname: Miller
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Jim
authors.initials: J
authors.lastname: Mintz
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hellemann
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Ralph
authors.initials: R
authors.lastname: Kupka
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Leverich
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Altshuler
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
authors.affiliation: From the VA Palo Alto Health Care System, Palo Alto, and the Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, Calif.; the Department of Psychiatry, University of Texas Health Science Center, San Antonio; the Department of Psychiatry, UCLA, Los Angeles; the Department of Psychiatry, Mayo Clinic, Rochester, Minn.; the Lindner Center of HOPE, University of Cincinnati, Mason, Ohio; University Medical Center Groningen, University of Groningen, the Netherlands; the Altrecht Institute for Mental Health Care, Utrecht, and VU University Medical Centre Amsterdam, VU University Amsterdam, the Netherlands; the Biological Psychiatry Branch, NIMH, Bethesda, Md.; the Department of Psychiatry and Psychotherapy, Paracelsus Medical University, and Christian Doppler Klinik, Salzburg, Austria; and the School of Medicine and Health Sciences, George Washington University, Washington, D.C.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology*; D015897:Comorbidity; D003527:Cyclothymic Disorder / Q000453:epidemiology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D012737:Sex Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult