Depression research: where are we now?

Abstract

Extensive studies have led to a variety of hypotheses for the molecular basis of depression and related mood disorders, but a definite pathogenic mechanism has yet to be defined. The monoamine hypothesis, in conjunction with the efficacy of antidepressants targeting monoamine systems, has long been the central topic of depression research. While it is widely embraced that the initiation of antidepressant efficacy may involve acute changes in monoamine systems, apparently, the focus of current research is moving toward molecular mechanisms that underlie long-lasting downstream changes in the brain after chronic antidepressant treatment, thereby reaching for a detailed view of the pathophysiology of depression and related mood disorders. In this minireview, we briefly summarize major themes in current approaches to understanding mood disorders focusing on molecular views of depression and antidepressant action.

Figure 1

Approaches to the development of antidepressants targeting non-monoaminergic components. Chronic stress can cause hypercortisolemia which results in neuronal damages in the hippocampus, thereby weakening the feedback inhibition on HPA axis. Chronic stress also can inhibit the expression of neurotrophic factors through epigenetic mechanisms. On the other hand, chronic treatment of antidepressants and mood stabilizers can establish epigenomic environments that favor the expression of anti-depression genes. The targets may include genes for neurotrophic factors which prevent neuronal damages and enhance hippocampal neurogenesis. Some of approaches to the development of antidepressants targeting non-monoaminergic components are also shown.