Reduced prefrontal cortex DARPP-32 mRNA in completed suicide victims with schizophrenia.
Dopamine-and-cAMP-regulated neuronal phosphoprotein (32 kDa) (DARPP-32), encoded by PPP1R1B, is expressed in brain regions receiving dopaminergic projections, including the prefrontal cortex (PFC), and is implicated in the pathophysiology of schizophrenia. The broad functional capacity of DARPP-32 has potential relevance to both psychotic and negative symptoms of schizophrenia. We wished to determine if DARPP-32 gene expression and variation at selected SNPs correlated significantly with patient phenotypes. We performed RT-PCR to quantify DARPP-32 mRNA from brain samples (Brodmann Area 46) donated by the Stanley Medical Research Institute (SMRI, Array Collection): 35 from unaffected controls (UC), 35 from patients with schizophrenia (SCZ), and 35 with bipolar disorder (BP). Relative mRNA expression was calculated in relation to the housekeeping gene Cyclophilin. SNP genotyping was conducted by PCR on DNA obtained from Brodmann Area 46. We found a significant difference in gene expression levels between SCZ patients who died by suicide (SCZ-S) (n=6) vs. other causes of death (SCZ-NS) (P<0.004), as well as between SCZ-S and UC (P<0.04). We genotyped the intron SNP rs907094 and found that the SCZ-S group was more similar to UC than to the SCZ-NS population. DARPP-32 expression differences between SCZ-S, SCZ-NS, and UC populations are consistent with previous literature suggesting that serotonin system components are also altered in suicide. Work in a larger sample is needed to confirm these findings.
Feldcamp
Laura A
LA
Department of Pharmacology, University of Toronto, 250 College St., M5T1R8, Toronto, Canada. l.feldcamp@utoronto.ca
Souza
Renan P
RP
Romano-Silva
Marco
M
Kennedy
James L
JL
Wong
Albert H C
AH
D000328:Adult; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D021983:Cyclophilins / Q000235:genetics; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017397:Prefrontal Cortex / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013405:Suicide / Q000523:psychology*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human; D012333:RNA, Messenger; D021983:Cyclophilins