Anterior cingulate pyramidal neurons display altered dendritic branching in depressed suicides

Background: It is hypothesized that mood disorders are accompanied by altered wiring and plasticity in key limbic brain regions such as the anterior cingulate cortex (ACC). To test this hypothesis at the cellular level, we analyzed basilar dendritic arborizations extended by layer VI pyramidal neurons in silver-impregnated postmortem ACC samples from well-characterized depressed suicide subjects (n = 12) and matched sudden-death controls (n = 7). Methods: One cm(3) tissue blocks were stained using a Golgi preparation, cut on a microtome, and mounted on slides. Basilar dendritic arbors from 195 neurons were reconstructed, and the number, length, and diameter of branches were determined at each branch order. The size and number of spines borne by these branches were also assessed. Results: Third-order branches were significantly reduced in number (24% fewer; p = 0.00262) in depressed suicides compared to controls. The size and average length of these branches, as well as their number of spines/length were unaltered. On average, for each pyramidal neuron analyzed in depressed subjects, the fewer third-order branches resulted in a significant reduction in branch length (28% shorter; p = 0.00976) at this branch order. Conclusions: These results provide the first evidence of altered cortical dendritic branching in mood disorders. Given that proximal dendritic branches grow during perinatal development, and that they are generally less plastic at maturity than distal segments, we speculate that these differences in dendritic branching may reflect a biological predisposition to depression and suicide. (C) 2009 Elsevier Ltd. All rights reserved.