Featured Finding Figure
Seven distinct 14-3-3 proteins are expressed in mammals. The current study sought to analyze the expression of all 14-3-3 genes in the prefrontal cortex (PFC) of subjects with schizophrenia. cDNA microarrays and RT-PCR were used to assess the levels of 14-3-3 gene transcripts in subjects with schizophrenia and matched controls. Selected changes in gene expression were further examined using in situ hybridization in the same subject pairs, as well as in monkeys treated chronically with haloperidol and matched control animals. Each of the 14-3-3 genes was expressed in the PFC of human subjects by RT-PCR. Microarray analysis indicated that the majority of 14-3-3 genes exhibited moderate to marked decreases in expression in schizophrenia which were significant at the group level across all comparisons (p<.021), as shown in Panel A. The fluorescent signal intensity for each matched subject pair is plotted on a log scale. The dashed line indicates equal expression, whereas the solid line indicates two fold changes in expression. In situ hybridization analysis and multivariate analysis of covariance confirmed the significant decreases in expression of two 14-3-3 genes: beta -31.9%, zeta -18.2% (see Panel B). The mean Z score for each transcript is indicated by the solid bar. Notably, only the beta and zeta genes had mean Z scores less than -1.96 (the two tailed cutoff for significance) across the 10 subject pairs. Two other 14-3-3 genes exhibited more modest decreases in expression levels that were significant only in pairwise comparisons that did not factor in postmortem interval or tissue storage time: gamma -11.9%, eta -15.4%. In the PFC of haloperidol-treated monkeys, there was no difference in 14-3-3 zeta expression, while 14-3-3 beta increased 28% (p < .05) as a result of treatment. Decreased expression of selected 14-3-3 genes is a common feature of schizophrenia; in our cohort, the most severely affected of the 14-3-3 genes (beta and zeta) were those not previously associated with schizophrenia. The 14-3-3 beta transcript may be unique among the 14-3-3 genes in its increase in response to haloperidol and decrease in the disease state.
Middleton FA, Peng L, Lewis DA, Levitt P, Mirnics K: Altered expression of 14-3-3 genes in the prefrontal cortex of subjects with schizophrenia. Neuropsychopharmacology 30: 974-983, 2005.

• Translational Neuroscience Program •
| Home |

David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
Pittsburgh, Pennsylvania 15213-2593
Phone: (412) 624-3894 - Fax: (412) 624-9910