On the neurobiology of depression: research based on heterogeneous diagnostic groups produces heterogeneous biological data.

An improvement in the accuracy and specificity of the criteria for identifying people with major depressive disorder would be of great benefit not only in the diagnosis and treatment of patients with depression, but also in research concerning the biological substrates of the emotions. Unfortunately, attempts at developing a biological diagnostic test for depression based on the analysis of major depressive disorder patients identified on the basis of existing diagnostic criteria have not been successful. Undoubtedly, this is due in part to the complexity of the neurochemistry and neuroanatomy of the emotions. But more importantly, it is due to the broad global nature of the criteria used to identify depressed patients. This results in the biological study of patients who are similar in general terms but who differ in specific behavioral symptoms and underlying neurobiology. A detailed analysis of the behavior of depressed people might reveal subtle differences that could be used to separate patients with depression into more homogeneous subgroups for biological study. This would increase the probability of developing biological tests that would lead to further refinement in the diagnosis of depression and in the selection of the most appropriate therapeutic intervention for a particular patient.