Endophenotypes and Research Domain Criteria (RDoC) represent recent efforts to deconvolute psychiatric illnesses into fundamental symptom clusters or biological markers more closely linked to genetic influences. By taking this one step farther, these biomarkers can be reduced to protophenotypes - endophenotypes conserved during evolution - with counterparts in lower organisms including Caenorhabditis elegans and Drosophila. Striking conservation in C. elegans of genes that increase the risk for mental illness bolsters the relevance of this model system for psychiatric research. Here, I review the characterization of several protophenotypes that are relevant for asociality, avolition/anhedonia, prepulse inhibition, and anorexia. Interestingly, the analogous behavioral defects in C. elegans are also corrected by psychotropic drugs used to treat the corresponding symptoms in man and/or are mediated by the same neurotransmitters. Overall, there is much we can learn about the complex human brain by studying simpler nervous systems directing evolutionarily conserved behaviors. The potential for generating important new insights from model organisms appears limitless when we begin to recognize the vestiges of evolution in ourselves.
Keywords: Anorexia; Antidepressants; Antipsychotics; Endophenotypes; Major depressive disorder; Protophenotypes; Schizophrenia.