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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

Pharmacotherapeutics

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