Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2013

Open Access 01-12-2013 | Debate

Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia

Authors: Victoria E Cosgrove, Trisha Suppes

Published in: BMC Medicine | Issue 1/2013

Login to get access

Abstract

Background

The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) opted to retain existing diagnostic boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia. The debate preceding this decision focused on understanding the biologic basis of these major mental illnesses. Evidence from genetics, neuroscience, and pharmacotherapeutics informed the DSM-5 development process. The following discussion will emphasize some of the key factors at the forefront of the debate.

Discussion

Family studies suggest a clear genetic link between bipolar I disorder, schizoaffective disorder, and schizophrenia. However, large-scale genome-wide association studies have not been successful in identifying susceptibility genes that make substantial etiological contributions. Boundaries between psychotic disorders are not further clarified by looking at brain morphology. The fact that symptoms of bipolar I disorder, but not schizophrenia, are often responsive to medications such as lithium and other anticonvulsants must be interpreted within a larger framework of biological research.

Summary

For DSM-5, existing nosological boundaries between bipolar I disorder and schizophrenia were retained and schizoaffective disorder preserved as an independent diagnosis since the biological data are not yet compelling enough to justify a move to a more neurodevelopmentally continuous model of psychosis.
Appendix
Available only for authorised users
Literature
1.
Deconstructing Psychosis: Refining the Research Agenda for DSM-V. Edited by: Tamminga CA, Sirovatka PJ, Regier DA, Os J van. 2010, Arlington, VA: American Psychiatric Association
2.
3.
Kawa S, Giordano J: A brief historicity of the Diagnostic and Statistical Manual of Mental Disorders: issues and implications for the future of psychiatric canon and practice. Philos Ethics Humanit Med. 2012, 7: 2-10.1186/1747-5341-7-2.CrossRefPubMedPubMedCentral
4.
Patil T, Giordano J: On the ontological assumptions of the medical model of psychiatry: philosophical considerations and pragmatic tasks. Philos Ethics Humanit Med. 2010, 5: 3-10.1186/1747-5341-5-3.CrossRefPubMedPubMedCentral
5.
Farah MJ, Gillihan SJ: The puzzle of neuroimaging and psychiatric diagnosis: technology and nosology in an evolving discipline. AJOB Neurosci. 2012, 3: 31-41.CrossRefPubMedPubMedCentral
6.
Robins E, Guze SB: Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiatry. 1970, 126: 983-987.CrossRefPubMed
7.
Radden JH: Recognition rights, mental health consumers and reconstructive cultural semantics. Philos Ethics Humanit Med. 2012, 7: 6-10.1186/1747-5341-7-6.CrossRefPubMedPubMedCentral
8.
Silverstein SM, Bellack AS: A scientific agenda for the concept of recovery as it applies to schizophrenia. Clin Psychol Rev. 2008, 28: 1108-1124. 10.1016/j.cpr.2008.03.004.CrossRefPubMed
9.
Lysaker PH, Roe D, Buck KD: Recovery and wellness amidst schizophrenia: definitions, evidence, and the implications for clinical practice. J Am Psychiatr Nurses Assoc. 2010, 16: 36-42. 10.1177/1078390309353943.CrossRefPubMed
10.
Rosen LN, Rosenthal NE, Dunner DL, Fieve RR: Social outcome compared in psychotic and nonpsychotic bipolar I patients. J Nerv Ment Dis. 1983, 171: 272-275. 10.1097/00005053-198305000-00002.CrossRefPubMed
11.
Abrams DJ, Rojas DC, Arciniegas DB: Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat. 2008, 4: 1089-1109.CrossRefPubMedPubMedCentral
12.
Malhi GS, Green M, Fagiolini A, Peselow ED, Kumari V: Schizoaffective disorder: diagnostic issues and future recommendations. Bipolar Disord. 2008, 10: 215-230. 10.1111/j.1399-5618.2007.00564.x.CrossRefPubMed
13.
Ivleva EI, Morris DW, Moates AF, Suppes T, Thaker GK, Tamminga CA: Genetics and intermediate phenotypes of the schizophrenia–bipolar disorder boundary. Neurosci Biobehav Rev. 2010, 34: 897-921. 10.1016/j.neubiorev.2009.11.022.CrossRefPubMed
14.
O’Donovan MC, Craddock NJ, Owen MJ: Genetics of psychosis; insights from views across the genome. Hum Genet. 2009, 126: 3-12. 10.1007/s00439-009-0703-0.CrossRefPubMed
15.
16.
Jäger M, Haack S, Becker T, Frasch K: Schizoaffective disorder–an ongoing challenge for psychiatric nosology. Eur Psychiatry. 2011, 26: 159-165.CrossRefPubMed
17.
Phillips J, Frances A, Cerullo MA, Chardavoyne J, Decker HS, First MB, Ghaemi N, Greenberg G, Hinderliter AC, Kinghorn WA, LoBello SG, Martin EB, Mishara AL, Paris J, Pierre JM, Pies RW, Pincus HA, Porter D, Pouncey C, Schwartz MA, Szasz T, Wakefield JC, Waterman GS, Whooley O, Zachar P: The six most essential questions in psychiatric diagnosis: a pluralogue part 1: conceptual and definitional issues in psychiatric diagnosis. Philos Ethics Humanit Med. 2012, 7: 3-10.1186/1747-5341-7-3.CrossRefPubMedPubMedCentral
18.
Phillips J, Frances A, Cerullo MA, Chardavoyne J, Decker HS, First MB, Ghaemi N, Greenberg G, Hinderliter AC, Kinghorn WA, LoBello SG, Martin EB, Mishara AL, Paris J, Pierre JM, Pies RW, Pincus HA, Porter D, Pouncey C, Schwartz MA, Szasz T, Wakefield JC, Waterman GS, Whooley O, Zachar P: The six most essential questions in psychiatric diagnosis: a pluralogue part 2: Issues of conservatism and pragmatism in psychiatric diagnosis. Philos Ethics Humanit Med. 2012, 7: 8-10.1186/1747-5341-7-8.CrossRefPubMedPubMedCentral
19.
Phillips J, Frances A, Cerullo MA, Chardavoyne J, Decker HS, First MB, Ghaemi N, Greenberg G, Hinderliter AC, Kinghorn WA, LoBello SG, Martin EB, Mishara AL, Paris J, Pierre JM, Pies RW, Pincus HA, Porter D, Pouncey C, Schwartz MA, Szasz T, Wakefield JC, Waterman GS, Whooley O, Zachar P: The six most essential questions in psychiatric diagnosis: a pluralogue part 3: issues of utility and alternative approaches in psychiatric diagnosis. Philos Ethics Humanit Med. 2012, 7: 9-10.1186/1747-5341-7-9.CrossRefPubMedPubMedCentral
20.
Phillips J, Frances A, Cerullo MA, Chardavoyne J, Decker HS, First MB, Ghaemi N, Greenberg G, Hinderliter AC, Kinghorn WA, LoBello SG, Martin EB, Mishara AL, Paris J, Pierre JM, Pies RW, Pincus HA, Porter D, Pouncey C, Schwartz MA, Szasz T, Wakefield JC, Waterman GS, Whooley O, Zachar P: The six most essential questions in psychiatric diagnosis: a pluralogue. Part 4: general conclusion. Philos Ethics Humanit Med. 2012, 7: 14-10.1186/1747-5341-7-14.CrossRefPubMedPubMedCentral
21.
Kraepelin E: Psychiatrie. 1899, Leipzig: Barth, 6
22.
Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P: Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010, 167: 748-751. 10.1176/appi.ajp.2010.09091379.CrossRefPubMed
23.
Caspi A, Moffitt TE: Gene-environment interactions in psychiatry: joining forces with neuroscience. Nat Rev Neurosci. 2006, 7: 583-590.CrossRefPubMed
24.
Wurzman R, Giordano J: Differential susceptibility to plasticity: a ‘missing link’ between gene-culture co-evolution and neuropsychiatric spectrum disorders?. BMC Med. 2012, 10: 37-10.1186/1741-7015-10-37.CrossRefPubMedPubMedCentral
25.
Belsky J, Pluess M: Beyond diathesis stress: differential susceptibility to environmental influences. Psychol Bull. 2009, 135: 885-908.CrossRefPubMed
26.
Tsuang MT, Winokur G, Crowe RR: Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br J Psychiatry. 1980, 137: 497-504. 10.1192/bjp.137.6.497.CrossRefPubMed
27.
Mortensen PB, Pedersen CB, Melbye M, Mors O, Ewald H: Individual and familial risk factors for bipolar affective disorders in Denmark. Arch Gen Psychiatry. 2003, 60: 1209-1215. 10.1001/archpsyc.60.12.1209.CrossRefPubMed
28.
Lichtenstein P, Yip BH, Björk C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM: Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009, 373: 234-239. 10.1016/S0140-6736(09)60072-6.CrossRefPubMed
29.
Van Snellenberg JX, De Candia T: Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch Gen Psychiatry. 2009, 66: 748-755. 10.1001/archgenpsychiatry.2009.64.CrossRefPubMed
30.
Dean K, Stevens H, Mortensen PB, Murray RM, Walsh E, Pedersen CB: Full spectrum of psychiatric outcomes among offspring with parental history of mental disorder. Arch Gen Psychiatry. 2010, 67: 822-829. 10.1001/archgenpsychiatry.2010.86.CrossRefPubMed
31.
Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI, Goldin LR, Bunney WE: A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry. 1982, 39: 1157-10.1001/archpsyc.1982.04290100031006.CrossRefPubMed
32.
Maier W, Lichtermann D, Minges J, Hallmayer J, Heun R, Benkert O, Levinson DF: Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch Gen Psychiatry. 1993, 50: 871-10.1001/archpsyc.1993.01820230041004.CrossRefPubMed
33.
Kendler KS, Karkowski LM, Walsh D: The structure of psychosis: latent class analysis of probands from the Roscommon Family Study. Arch Gen Psychiatry. 1998, 55: 492-499. 10.1001/archpsyc.55.6.492.CrossRefPubMed
34.
Cardno AG, Rijsdijk FV, Sham PC, Murray RM, McGuffin P: A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry. 2002, 159: 539-545. 10.1176/appi.ajp.159.4.539.CrossRefPubMed
35.
Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N: The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry. 2009, 15: 101698.
36.
37.
Lee KW, Woon PS, Teo YY, Sim K: Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: what have we learnt?. Neurosci Biobehav Rev. 2012, 36: 556-571. 10.1016/j.neubiorev.2011.09.001.CrossRefPubMed
38.
Ellison-Wright I, Bullmore E: Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophr Res. 2010, 11: 1-12.CrossRef
39.
Arnone D, Cavanagh J, Gerber D, Lawrie SM, Ebmeier KP, McIntosh AM: Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. Br J Psychiatry. 2009, 195: 194-201. 10.1192/bjp.bp.108.059717.CrossRefPubMed
40.
Rimol LM, Nesvåg R, Hagler DJ, Bergmann O, Fennema-Notestine C, Hartberg CB, Haukvik UK, Lange E, Pung CJ, Server A, Melle I, Andreassen OA, Agartz I, Dale AM: Cortical volume, surface area, and thickness in schizophrenia and bipolar disorder. Biol Psychiatry. 2012, 71: 552-560. 10.1016/j.biopsych.2011.11.026.CrossRefPubMed
41.
McIntosh AM, Job DE, Moorhead WJ, Harrison LK, Whalley HC, Johnstone EC, Lawrie SM: Genetic liability to schizophrenia or bipolar disorder and its relationship to brain structure. Am J Med Genet B Neuropsychiatr Genet. 2006, 141B: 76-83. 10.1002/ajmg.b.30254.CrossRefPubMed
42.
Hulshoff Pol HE, Van Baal GCM, Schnack HG, Brans RGH, Van der Schot AC, Brouwer RM, van Haren NE, Lepage C, Collins DL, Evans AC, Boomsma DI, Nolen W, Kahn RS: Overlapping and segregating structural brain abnormalities in twins with schizophrenia or bipolar disorder. Arch Gen Psychiatry. 2012, 69: 349-359. 10.1001/archgenpsychiatry.2011.1615.CrossRefPubMed
43.
Suppes T, Baldessarini RJ, Faedda GL, Tohen M: Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Arch Gen Psychiatry. 1991, 48: 1082-1088. 10.1001/archpsyc.1991.01810360046007.CrossRefPubMed
44.
Schulz SC, Thompson PA, Jacobs M, Ninan PT, Robinson D, Weiden PJ, Yadalam K, Glick ID, Odbert CL: Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients. J Clin Psychiatry. 1999, 60: 366.CrossRefPubMed
45.
Baldessarini RJ, Viguera AC, Tondo L: Discontinuing psychotropic agents. J Psychopharmacol. 1999, 13: 292-293. 10.1177/026988119901300314. discussion 299CrossRefPubMed
46.
Leucht S, Kissling W, McGrath J: Lithium for schizophrenia. Cochrane Database Syst Rev. 2007, 3: CD003834
47.
Casey DE, Daniel DG, Wassef AA, Tracy KA, Wozniak P, Sommerville KW: Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Neuropsychopharmacology. 2003, 28: 182-192. 10.1038/sj.npp.1300023.CrossRefPubMed
48.
Tiihonen J, Hallikainen T, Ryynänen O-P, Repo-Tiihonen E, Kotilainen I, Eronen M, Toivonen P, Wahlbeck K, Putkonen A: Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Biol Psychiatry. 2003, 54: 1241-1248. 10.1016/S0006-3223(03)00524-9.CrossRefPubMed
49.
Kremer I, Vass A, Gorelik I, Bar G, Blanaru M, Javitt DC, Heresco-Levy U: Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biol Psychiatry. 2004, 56: 441-446. 10.1016/j.biopsych.2004.06.029.CrossRefPubMed
50.
Zoccali R, Muscatello MR, Bruno A, Cambria R, Micentional , Meduri M: The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr Res. 2007, 93: 109-116. 10.1016/j.schres.2007.02.009.CrossRefPubMed
51.
Goff DC, Keefe R, Citrome L, Davy K, Krystal JH, Large C, Thompson TR, Volavka J, Webster EL: Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials. J Clin Psychopharmacol. 2007, 27: 582-589. 10.1097/jcp.0b013e31815abf34.CrossRefPubMed
52.
Post RM: Comparative pharmacology of bipolar disorder and schizophrenia. Schizophr Res. 1999, 39: 153-158. 10.1016/S0920-9964(99)00115-2. discussion 163CrossRefPubMed
53.
Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, Venturi P, Jones LA, Lewis SW, Sham PC, Gottesman II, Farmer AE, McGuffin P, Reveley AM, Murray RM: Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry. 1999, 56: 162-168. 10.1001/archpsyc.56.2.162.CrossRefPubMed
54.
55.
Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N, Wellcome Trust Case Control Consortium: The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry. 2009, 15: 1016-1022.CrossRefPubMedPubMedCentral
56.
McDonald C, Bullmore E, Sham P, Chitnis X, Suckling J, MacCabe J, Walshe M, Murray RM: Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: computational morphometry study. Br J Psychiatry. 2005, 186: 369-377. 10.1192/bjp.186.5.369.CrossRefPubMed
57.
McDonald C, Marshall N, Sham PC, Bullmore ET, Schulze K, Chapple B, Bramon E, Filbey F, Quraishi S, Walshe M, Murray RM: Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. Am J Psychiatry. 2006, 163: 478-487. 10.1176/appi.ajp.163.3.478.CrossRefPubMed
58.
McDonald C, Bullmore ET, Sham PC, Chitnis X, Wickham H, Bramon E, Murray RM: Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiatry. 2004, 61: 974-984. 10.1001/archpsyc.61.10.974.CrossRefPubMed
59.
Stahl SM: Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2008, Cambridge, UK: Cambridge University Press
60.
Goodwin FK: Rationale for long-term treatment of bipolar disorder and evidence for long-term lithium treatment. J Clin Psychiatry. 2002, 63: 5-12.PubMed
61.
Schwarz C, Volz A, Li C, Leucht S: Valproate for schizophrenia. Cochrane Database Syst Rev. 2008, 3: CD004028
62.
Amann B, Born C, Crespo JM, Pomarol-Clotet E, McKenna P: Lamotrigine: when and where does it act in affective disorders? A systematic review. J Psychopharmacol. 2011, 25: 1289-1294. 10.1177/0269881110376695.CrossRefPubMed
63.
Goodwin FK, Jamison KR: Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. 2007, New York: Oxford University Press, 2
Metadata
Title
Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia
Authors
Victoria E Cosgrove
Trisha Suppes
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-11-127

Other articles of this Issue 1/2013

BMC Medicine 1/2013 Go to the issue

Commentary

Pre-hypertension: another 'pseudodisease’?

Research article

The Academic Backbone: longitudinal continuities in educational achievement from secondary school and medical school to MRCP(UK) and the specialist register in UK medical students and doctors

Review

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis

Commentary

Causes of death after fluid bolus resuscitation: new insights from FEAST

Research article

Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis

Question and Answer

The DSM-5 - an interview with David Kupfer