PMID- 32684621 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20220422 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 10 IP - 1 DP - 2020 Jul 19 TI - Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study. PG - 241 LID - 10.1038/s41398-020-00922-2 [doi] LID - 241 AB - A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p < 0.001) but ANOVA revealed that significant between-group differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researched-based definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression. FAU - Corponi, Filippo AU - Corponi F AUID- ORCID: 0000-0002-6807-0617 AD - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. FAU - Anmella, Gerard AU - Anmella G AUID- ORCID: 0000-0002-6798-4054 AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. FAU - Pacchiarotti, Isabella AU - Pacchiarotti I AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. AD - Biomedical Research Networking Center for Mental Health (CIBERSAM), Barcelona, Spain. AD - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. FAU - Samalin, Ludovic AU - Samalin L AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. FAU - Verdolini, Norma AU - Verdolini N AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. AD - Biomedical Research Networking Center for Mental Health (CIBERSAM), Barcelona, Spain. AD - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. FAU - Popovic, Dina AU - Popovic D AD - Psychiatry B, Chaim Sheba Medical Center, Ramat-Gan, Israel. FAU - Azorin, Jean-Michel AU - Azorin JM AD - Department of Psychiatry, Sainte Marguerite Hospital, Marseille, France. FAU - Angst, Jules AU - Angst J AD - Department of Psychiatry, University of Zurich, Zurich, Switzerland. FAU - Bowden, Charles L AU - Bowden CL AD - Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA. FAU - Mosolov, Sergey AU - Mosolov S AUID- ORCID: 0000-0002-5749-3964 AD - Department for Therapy of Mental Disorders, Moscow Research Institute of Psychiatry, Moscow, Russia. FAU - Young, Allan H AU - Young AH AUID- ORCID: 0000-0003-2291-6952 AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Centre for Affective Disorders, London, UK. FAU - Perugi, Giulio AU - Perugi G AD - Clinica Psichiatrica, University of Pisa, Pisa, Italy. FAU - Vieta, Eduard AU - Vieta E AUID- ORCID: 0000-0002-0548-0053 AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. evieta@clinic.cat. AD - Biomedical Research Networking Center for Mental Health (CIBERSAM), Barcelona, Spain. evieta@clinic.cat. AD - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. evieta@clinic.cat. FAU - Murru, Andrea AU - Murru A AUID- ORCID: 0000-0001-6320-4420 AD - Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. AD - Biomedical Research Networking Center for Mental Health (CIBERSAM), Barcelona, Spain. AD - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20200719 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 SB - IM MH - *Bipolar Disorder/diagnosis MH - Cluster Analysis MH - *Depressive Disorder, Major/diagnosis MH - Diagnostic and Statistical Manual of Mental Disorders MH - Humans MH - Prospective Studies PMC - PMC7370235 COIS- J.A., F.C., G.A., and N.V. declare no conflict of interest. I.P. has received CME-related honoraria, or consulting fees from ADAMED, Janssen-Cilag, and Lundbeck. L.S. has received grants, honoraria, or consulting fees from Janssen-Cilag, Lundbeck, and Otsuka. D.P. has served as a speaker and/or medical writer for Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen-Cilag, and Ferrer. J.M.A. has received research support and has acted as a consultant and/or served on a speaker's bureau for Janssen, Lundbeck, Otsuka, Roche, Servier, and Takeda, and reports no financial or other relationship relevant to the subject of this article. C.L.B. has received grant support from Sunovion and the NIMH, and has consulted for Takeda, and reports no financial or other relationship relevant to the subject of this article. S.M. has received research grants from, and been involved in clinical trials for Servier, Eli Lilly, Lundbeck, AstraZeneca, Janssen-Cilag, Sanofi-Aventis, and Geodon Richter and reports no financial or other relationship relevant to the subject of this article. A.H.Y. is honorary Consultant SLaM (NHS, UK). He provided lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Janssen, Lunbeck, Sunovion, Servier, Livanova, and Janssen. He does not share holdings in pharmaceutical companies. He is Lead Investigator for Embolden Study (AZ), BCI Neuroplasticity study and Aripiprazole Mania Study, he did investigator initiated studies from AZ, Eli Lilly, Lundbeck, Wyeth. Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK);UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK). He reports no financial or other relationship relevant to the subject of this article. G.P. has acted as consultant of Lundbeck, Angelini, FBHealth. He received grant/research support from Lundbeck and Angelini. He is on the speaker/advisory board of Sanofi-Aventis, Lundbeck, FBHealth, Angelini, and reports no financial or other relationship relevant to the subject of this article. E.V. has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics,Abbott, Allergan, Angelini, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the EU Horizon 2020, and the Stanley Medical Research Institute. A.M. has received grants, honoraria, or consulting fees from, Janssen, Lundbeck, and Otsuka. EDAT- 2020/07/21 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/07/19 CRDT- 2020/07/21 06:00 PHST- 2020/02/20 00:00 [received] PHST- 2020/06/09 00:00 [accepted] PHST- 2020/06/07 00:00 [revised] PHST- 2020/07/21 06:00 [entrez] PHST- 2020/07/21 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/07/19 00:00 [pmc-release] AID - 10.1038/s41398-020-00922-2 [pii] AID - 922 [pii] AID - 10.1038/s41398-020-00922-2 [doi] PST - epublish SO - Transl Psychiatry. 2020 Jul 19;10(1):241. doi: 10.1038/s41398-020-00922-2.