Much evidence has been found linking major neuropsychiatric disorders to altered regulation of adult NSCs and to the molecular systems involved in their maintenance and differentiation. The SGZ of the DG has been the region of the most research focus. DG functioning underlies mood, memory, and reward, which are impaired in schizophrenia, major depression and bipolar disorder. In animal models of depression, schizophrenia, and bipolar disorder, the activity of SGZ stem cells is reduced. For example, chronic stress leads to a depression-like phenotype in rodents, suppresses neurogenesis in the SGZ and reduces FGF2 expression in hippocampus (Warner-Schmidt and Duman, 2006). Findings from post mortem studies have demonstrated that numbers of proliferating cells in the DG are decreased in psychotic disorders (Reif et al., 2006); furthermore, abnormal FGF expression has been documented in the post mortem hippocampus of depressed and schizophrenic patients (Gaughran et al., 2006). In this study, neither antidepressant treatment nor the presence of affective disorders were found to be correlated with altered numbers of hippocampal dividing cells. However, other post mortem work has demonstrated that patients who received antidepressant treatment did show a greater number of neural progenitor and dividing cells in the DG than untreated patients with depression (Boldrini et al., 2009). Furthermore, antidepressant treatment increases hippocampal neurogenesis in both rodents (Malberg et al., 2000) and non-human primates (Perera et al., 2007). Chronic antidepressant administration to rodents has been shown to increase FGF2 expression in astrocytes and neurons within and outside of the hippocampus, suggesting that FGF signaling may be involved in the neurogenic action of antidepressants. In support of this idea, the infusion of FGF2 into the ventricles of adult rats increases cell proliferation and reduces depression-like behavior in rodents (Turner et al., 2008). Also, conditional knockout of fgfr1 in neuronal stem cells by nestin-Cre results in reduced proliferation and neurogenesis in the adult DG (Zhao et al., 2007). New data suggest FGF2 may be specifically involved in the modulation of anxiety/fear behavior in rodents (Perez et al., 2009). However, it is currently controversial whether ongoing hippocampal neurogenesis is required for the therapeutic action of antidepressants. Some have proposed that hippocampal neurogenesis may be limited to mediating the beneficial action of antidepressants on cognition. One problem is the limitations of animal models of depression in which behavior may rely on mechanisms that are peripheral to human disease (Santarelli et al., 2003; Sahay and Hen, 2007; Holick et al., 2008; David et al., 2009). Hence, the specific role of FGF2 on the development and function of systems that subserve affective and cognitive functions in humans is still somewhat unclear.