Both genes and environment play a role in depression. Data indicate that in addition to monoamines, other endogenous compounds, such as neuropeptides, as well as hippocampal cell loss/neurogenesis may be important in pathophysiology and treatment of depression. Finally, it is not clear whether early intervention could alleviate or prevent the disorder. Consequently, we studied neuropeptides in animal models: (i) a genetic model, the Flinders Sensitive Line (FSL) rat and their controls, FRL line, (ii) an environmental model, early maternal separation that mimics early life trauma in humans - experiences that predict adult life psychopathology, and (iii) maternal separation superimposed on the genetic FSL model

Behavior was studied when the animals reached adulthood, and brain neurochemistry and cell proliferation postmortem. On postnatal days (PND) 2–14, FSL and FRL pups were maternally separated for 180. Escitalopram or vehicle were started on PND 44. Porsolt swim test was done on PND 64-65.

baseline FSL-FRL differences were found in the Porsolt swim test and in brain neuropeptides, in particular NPY and CGRP in selected brain regions. Cell proliferation was also affected. Moreover, maternal separation and escitalopram also differentiated between the strains.

Both genes and environment play a role in “depression” but the consequences of early life events are more deleterious in genetically vulnerable individuals. Neurochemical, in particular NPY and CRH, and cell proliferation changes indicate that we may have identified some biological correlates of depression. potential strategy to alleviate adult life psychopathology.

The European Commission GENDEP project LSHB-CT-2003-503428; The Lundbeck Foundation.