Neurobiological basis of depression: an update

The past 5 years have seen unprecedented advances in our knowledge about the neurobiology of depression. Significant breakthroughs have been made in genomics, imaging, and the identification of key neural systems involved in cognition, emotion, and behavior. In addition, novel targets have been identified for the development of new pharmacological and behavioral treatments. Genetic variations associated with most mental disorders are being identified, and reliable tests for early detection of risk and disease are now on the horizon. New neurobiological concepts have emerged, as they relate to these advances in mental health research such as the serotonin transporter receptor, a genetic variant of which doubles the risk of depression. Brain neurochemicals, including neurotropic factors (implicated in several mental disorders), and anatomical studies involving imaging of the amygdala and the hippocampus and prefrontal cortex are now at the forefront. Several brain neurotransmitters systems: glutamate, gamma -aminobutyric acid, serotonin, norepinephrine, and dopamine have been implicated in depression and mania. These transmitter systems, as well as other neurochemical systems such as membrane-bound signal transduction systems and intracellular signaling systems that modulate gene transcription and protein synthesis, play an important role in the etiology of depression. This new knowledge is expected to provide important clues for the development of selective pharmacological interventions. Neuroimaging studies of depressed patients have shown several abnormalities of regional cerebral blood flow and glucose metabolism--a surrogate of neuronal function--in various brain regions, including the limbic cortex, the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. At this time, a considerable amount of new information is converging--derived from animal models of mood disorders, genetics, basic behavioral research, and neuroscience. It is inevitable that the next step in this progression will be the integration of these basic advances in clinical management and the application of this new information in the context of the depressed patient.