Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples.
Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many genes contributing to their etiologies. The aim of this investigation was to search for dysregulated molecular and cellular pathways for these disorders as well as psychosis. We conducted a blood-based microarray investigation in two independent samples with SCZ and BPD from San Diego (SCZ = 13, BPD = 9, control = 8) and Taiwan (SCZ = 11, BPD = 14, control = 16). Diagnostic groups were compared to controls, and subjects with a history of psychosis [PSYCH(+): San Diego (n = 6), Taiwan (n = 14)] were compared to subjects without such history [PSYCH(-): San Diego (n = 11), Taiwan (n = 14)]. Analyses of covariance comparing mean expression levels on a gene-by-gene basis were conducted to generate the top 100 significantly dysregulated gene lists for both samples by each diagnostic group. Gene lists were imported into Ingenuity Pathway Analysis (IPA) software. Results showed the ubiquitin proteasome pathway (UPS) was listed in the top ten canonical pathways for BPD and psychosis diagnostic groups across both samples with a considerably low likelihood of a chance occurrence (P = 0.001). No overlap in dysregulated genes populating these pathways was observed between the two independent samples. Findings provide preliminary evidence of UPS dysregulation in BPD and psychosis as well as support further investigation of the UPS and other molecular and cellular pathways for potential biomarkers for SCZ, BPD, and/or psychosis.
Bousman
Chad A
CA
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
Chana
Gursharan
G
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
Glatt
Stephen J
SJ
Department of Psychiatry and Behavioral Sciences, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York.
Chandler
Sharon D
SD
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
Lucero
Ginger R
GR
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
Tatro
Erick
E
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
May
Todd
T
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
Lohr
James B
JB
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
Kremen
William S
WS
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.|Veterans Affairs San Diego Healthcare System, San Diego, California.
Tsuang
Ming T
MT
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.|Harvard Institute of Psychiatric Epidemiology and Genetics, Harvard Departments of Epidemiology and Psychiatry, Boston, Massachusetts.|Veterans Affairs San Diego Healthcare System, San Diego, California.
Everall
Ian P
IP
Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*; D012984:Software; D013624:Taiwan; D025801:Ubiquitin / Q000235:genetics*
D012333:RNA, Messenger; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex