Figure 1.

VGF mRNA expression is reduced in bipolar disorder patients in the CA region of the hippocampus. A, Representative autoradiographic film images of hybridization of VGF antisense and sense probes in postmortem hippocampal sections. Boxed area in the antisense image is enlarged. ³⁵S-labeled antisense probe gives a strong signal in the subgranular zone and granule cell layer of the dentate gyrus and the pyramidal layer of the CA regions (CA1–CA3) as well as in the layers II–IV and VI of the inferior temporal lobe neocortex. The sense control probes give very low background hybridization. B, Expression of VGF mRNA in the hippocampus of bipolar disorder (BD) (n = 15), major depression (MD) (n = 14), and schizophrenia (SZ) (n = 13) samples are expressed as fold change of nonpsychiatric controls (represented by vertical line) (n = 15). Log of the expression levels were analyzed with a linear mixed-effects model, using diagnosis as a fixed effect and film and subject as random effects. Time in storage was used as a covariate. Estimates were found using the lme4 package in the R statistical environment, with nominal highest posterior density intervals determined by Markov Chain Monte Carlo. p values were found by repeatedly permuting diagnosis labels and comparing the observed test statistic against the most extreme test statistics of each permutation across all diagnostic comparisons with controls (for the result on the entire pyramidal cell layer of the CA regions) and simultaneously (for the region-specific results) over the four CA regions. A trend toward decreased expression in the CA regions of the hippocampus was detected in all diagnoses relative to nonpsychiatric controls with statistically significantly reduced expression in bipolar disorder (*p = 0.024). When the data were analyzed by subregion within the hippocampus, CA1b showed significantly reduced expression for bipolar disorder compared with nonpsychiatric controls (*p = 0.018), as did CA2 (*p = 0.046). Analysis of dentate gyrus includes the subgranular zone, the granule cell layer, and the hilar regions.