Figure 3. Dendritic inhibition, a biological module at the intersection of age and psychiatric disorders. A) Excitatory pyramidal neurons (PYR) are regulated by different types of inhibitory γ-aminobutyric acid (GABA) neurons. Somatostatin (SST)-, neuropeptide Y (NPY)- and cortistatin (CORT)-positive GABA neurons (red) target PYR distal dendrites. Parvalbumin- (PV) and cholecystokinin- (CCK) positive GABA neurons target PYR cell body and axon initial segment (blue). Calretinin-(CR) positive GABA neurons (green) regulate other GABA neurons. B) Markers of interneurons that target PYR dendrites show decreased expression with age, and great effect or statistical significance of changes in subjects with major depression. C) Brain-derived neurotropic factor (BDNF) expression, measured by quantitative polymerase chain reaction (qPCR), is significantly and inversely correlated with chronological age in control and depressed subjects. Values are in arbitrary units of qPCR signal intensity. Respective to age-matched control subjects, subjects with major depression display greater BDNF downregulation (-22%; P<0.05). D) Age-regulation of BDNF- and depression-related genes. The average relative age effects for each individual subject are shown for the set of BDNF-related genes that display significant depression-related effects. Microarray-based gene expression values were normalized to the group means of each gene and averaged per subject. The BDNF-related gene set was split based on the effect of age on those genes in control subjects (top panel, age-upregulated; bottom panel, age-downregulated). The results show that age effects are systematically in the same direction, and of greater effect sizes in subjects with major depression (red squares) compared with controls (blue circles). Values are Pearson correlation factors. *, P<0.05; **, P<0.01 . Data in B is from Erraji et al,⁷ Glorioso et al,¹⁹ and Guilloux et al.¹⁴ Figures C and D are adapted from ref 18: Douillard-Guilloux G, Guilloux JP, Lewis DA, Sibille E. Anticipated brain molecular aging in Major Depression. Am J Geriatr Psychiatry. 2012. Oct 31 [epub ahead of print]. Copyright © American Psychiatry Press 2012.