A second way outbreeding depression can occur is by the breakdown of biochemical or physiological compatibilities between genes in the different populations. Within local, isolated populations, alleles are selected for their positive, overall effects on the local genetic background. Due to nonadditive gene action, the same genes may have rather different average effects in different genetic backgrounds--hence, the potential evolution of locally coadapted gene complexes.
In other words, individuals from Population A will tend to have genes selected for the quality of combining well with gene combinations common in Population A. However, genes found in Population A will not have been selected for the quality of crossing well with genes common in Population B. Therefore outbreeding can undermine vitality by reducing positive epistasis and/or increasing negative epistasis.
However, it is critical to understand that reduced inbreeding depression in first generation hybrids can, in some circumstances, be strong enough to more than make up for outbreeding depression. This is why farmers keep purebred strains for the purpose of outcrossing (while not usually breeding the hybrids).
As a general rule of thumb, hybrid vigor (another way of saying a reduction of inbreeding depression) is strongest in first generation hybrids and gets weaker over time. In contrast, outbreeding depression can be relatively weak in the first generation. But outside the context of ruthless selective pressure, outbreeding depression will increase in power through the further generations as co-adapted gene complexes are broken apart without the forging of new co-adapted gene complexes to take their place.
It is important to keep in mind that these two mechanisms of outbreeding depression can be operating at the same time. However, determining which mechanism is more important in a particular population is very difficult.