POMC and bipolar disorder: Instead, emerging data suggest that upstream abnormalities (likely encoded in the nucleus) converge at mitochondrial function,38 leading to altered synaptic plasticity and impaired cellular resilience.41 Given the biphasic nature of bipolar disorder, it is hypothesized that the disorder represents a bi-directional state-dependent alteration in mitochondrial regulation.42 Our data presented here suggest that it may be possible to develop a new model of bipolar disorder with a biphasic mitochondrial and behavioral response to ACTH administration.