A logical relationship for schizophrenia, bipolar, and major depressive disorder. Part 1: Evidence from chromosome 1 high density association screen

Familial clustering of schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD) was investigated systematically (Aukes et al., Genetics in Medicine, 2012, 14, 338-341) and any two or even three of these disorders could coexist in some families. Furthermore, evidence from symptomatology and psychopharmacology also imply the existence of intrinsic connections between these three major psychiatric disorders. A total of 71,445 SNPs on chromosome 1 were genotyped on 119 SCZ, 253 BPD (type-I), 177 MDD cases and 1000 controls and further validated in 986 SCZ patients in the population of Shandong province of China. Outstanding psychosis genes are systematically revealed( ATP1A4, ELTD1, FAM5C, HHAT, KIF26B, LMX1A, NEGR1, NFIA, NR5A2, NTNG1, PAPPA2, PDE4B, PEX14, RYR2, SYT6, TGFBR3, TTLL7, and USH2A). Unexpectedly, flanking genes for up to 97.09% of the associated SNPs were also replicated in an enlarged cohort of 986 SCZ patients. From the perspective of etiological rather than clinical psychiatry, bipolar, and major depressive disorder could be subtypes of schizophrenia. Meanwhile, the varied clinical feature and prognosis might be the result of interaction of genetics and epigenetics, for example, irreversible or reversible shut down, and over or insufficient expression of certain genes, which may gives other aspects of these severe mental disorders.