The neurobiology of bipolar disorder: from circuits to cells to molecular regulation

Over the past 15 years, postmortem studies of the corticolimbic system in subjects with bipolar disorder (BPD) have demonstrated a variety of abnormalities affecting the gamma aminobutyric acid (GABA)ergic system. Although some of the changes are similar to those seen in individuals with schizophrenia, there are pronounced differences in the regulation of complex networks of genes involved in the expression of GAD67, a key marker for functionally differentiated GABAergic interneurons. Overall, these changes vary not only according to diagnosis, but also subregion and layer, suggesting that the activity of GABA cells in complex neural circuits are differentially affected by the unique extrinsic and intrinsic inputs that they receive at different points along a circuit like the trisynaptic pathway. Our ability to understand the functional implications in terms of complex molecular changes will ultimately influence our ability to develop novel treatments for BPD.