FIGURE 1.

(A) Somatostatin expression decreases with age in control subjects. Individuals with MDD (top panel) and schizophrenia (bottom panel) display lower levels of expression than control subjects at most ages, together prompting the hypothesis that decreased expression of somatostatin in depression and schizophrenia may represent early brain age-related molecular phenotypes in these individuals, which would render these subjects more vulnerable to developing psychiatric diseases. (B) Based on similar age and disease observations for numerous additional genes, we have proposed a model of “age-by-disease biological interaction” (Glorioso et al., 2011). In this model, change in expression of disease-related genes (a decrease is shown) across a threshold (horizontal blue line) marks the onset of disease symptoms. Changes in the trajectory of age-related changes in expression of disease-related genes (Y-axis) determine at what age (X-axis), or even if, an individual develops disease symptoms (vertical red arrows). Modulators (black arrows) may thus place an individual on “at risk” or “protected” trajectory. Per this model, individuals with LLD may have modulators, genetic or environmental, that place them on an “at risk” trajectory for developing mood symptoms. Figures are adapted from Morris et al. (2008), Tripp et al. (2011), Glorioso and Sibille (2011), and McKinney and Sibille (2012).