Hypothesis regarding variability in depression and anxiety observed one year after lumbar discectomy. Two types of genetic contribution to one-year mood scores are shown. (1) Mood genes currently studied by biological psychiatrists may contribute to the late mood effects of a stressful surgical illness. Because the diagnosis and treatment are shared by all participants, and one can measure residual pain and surgical delay as "environmental variables" and correct for their effect on moo, this design may enhance the sensitivity to detect gene effects, compared to designs that study affective disorders in patients with widely varying life stressors. These influences would show up in the statistical analysis as main effects on late mood. (2) Pain-mood genes may alter the direct effects of pain upon mood, possibly by effects on signaling molecules in the dense connections between spinal pain afferent inputs and mood-processing brain structures such as hypothalamus, amygdala, nucleus accumbens, medial orbital cortex, and cingulum. These gene effects would vary with the amount of residual chronic pain after surgery; i.e., they would show up as significant interactions between gene and pain levels in their effects upon mood.