Even neural stem cells get the blues: evidence for a molecular link between modulation of adult neurogenesis and depression.

An emerging hypothesis, linking modulation of neurogenesis with the onset and subsequent treatment of depression, has received much attention recently as an attractive explanation for successful behavioral changes induced by antidepressant medication in both humans and animals. However, evidence for such a link remains elusive and inconsistent. This review discusses evidence for modulation of neurogenesis as a neurobiological substrate for depression within the context of heterogeneous animal models of depression. Examining the evidence currently available linking neurogenesis and depression is problematic for at least four reasons: 1) approaches to document ongoing neurogenesis and neuronal lineage commitment are varied, making cross-study comparison difficult; 2) as the functional contribution of adult neurogenesis has yet to be completely determined, it is speculative to state a functional significance to changes in neurogenesis; 3) there is diversity in animal models of depression with variable degrees of correlation with human depression; and 4) there remains insufficient knowledge of molecular factors and changes in gene expression that conclusively link neurogenesis modulation and depression. This review examines the current state of evidence regarding the following: 1) consistent data collection delineating the existence of neurogenesis, its stages of progression, and stage modulation; 2) the functional contribution of adult hippocampal neurogenesis and the use of stress-based animal models for its modulation, 3) possible molecular links between antidepressant medication and neurogenesis, specifically neurotrophins and trophic factors; and finally 4) specific suggestions for further investigations necessary to warrant full acceptance of a link between modulation of neurogenesis and depression.