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Table 1 Summary of key evidence at the forefront of the boundaries of schizophrenia, schizoaffective disorder, and bipolar I disorder debate

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

Evidence Conclusion
Family studies
Tsuang et al., 1980 [26]; Mortensen et al., 2003 [27]; Lichtenstein et al., 2009 [28]; Van Snellenberg et al., 2009 [29]; Dean et al., 2010 [30] Increased risk for bipolar disorder in families of individuals with schizophrenia and for schizophrenia in families of individuals with bipolar disorder
Gershon et al., 1988 [31]; Maier et al. 1993 [32] Schizophrenia and bipolar disorder linked to unipolar depression
Kendler et al., 1998 [33] Roscommon Family Study; vulnerability to psychosis may extend across schizophrenia, major depression, and bipolar disorder
Twin studies
Cardno et al., 2002 [34] Significant genetic correlations between schizophrenia, schizoaffective disorder, and mania
Genome wide association studies (GWAS)
O’Donovan et al., 2009 [14]; Green et al., 2009 [35]; Williams et al., 2010 [36]; Lee et al., 2012 [37] ZNF804A and CACNA1C may influence risk for both schizophrenia and bipolar disorder
Brain morphology
Ellison-Wright and Bullmore, 2010 [38]; Arnone et al., 2009 [39]; Rimol et al., 2012 [40] Some overlapping white and gray matter deficits, but cortical reductions exclusive to schizophrenia
McIntosh et al., 2006 [41] Genetic liability for gray matter reductions in DLPRC and VLPFC exclusively in schizophrenia
Hulshoff et al., 2012 [42] Overlapping white matter volume and areas of thin cortex suggest shared neurodevelopment
Suppes et al., 1991 [43]; Schulz et al., 1999 [44]; Baldessarini et al., 1999 [45]; Leucht et al., 2006 [46] Lithium can be used as monotherapy or for augmentation of antipsychotics in bipolar disorder but ineffective in schizophrenia
Casey et al., 2003 [47] Divalproex prescribed for acute mania but minimal efficacy in schizophrenia
Tiihonen et al., 2003 [48]; Kremer et al., 2004 [49]; Zoccali et al., 2007 [50]; Goff et al., 2007 [51] Initial reports of lamotrigine positive in add-on schizophrenia, but no better than placebo in multicenter, randomized trials
Post et al., 1999 [52] Unexpected broad efficacy across psychotic disorders for second generation antipsychotics