William E. Bunney Jr.: Final comment
Thomas A. Ban:  Wernicke – Kleist – Leonhard tradition with special reference to mania, melancholia and manic–depressive psychosis
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            In my view Tom Ban has written an amazing, comprehensive, historical review on the "Fundamentals of the WKL Tradition" and the impact of a number of scholars on these concepts concerning mood disorders.   I believe these individuals have made highly significant contributions to our clinical understanding of these disorders.

            I also think that in the future we will continue to have sophisticated refinement of phenotypes and identification through hundreds of thousands of patients and controls, risk loci, genes and alleles associated with these illnesses.  Recently a paper was published in Nature Medicine identifying 15 risk loci using 130,620 patients and 347,620 controls.  It may be possible to use three new gene editing tools (CRISPRcas9 [Clustered Regularly Interspaced Short Palindromic Repeats], RNA Repair, and Base Editing) to correct genetic defects which allow one to delete or modify genes in the human genome.However, editing multiple genes as identified in these disorders currently presents a challenge. Also, in the future there will be a continued focus on identifying and treating vulnerable patients, some with newly discovered risk genes shared by schizophrenia and bipolar disorder, prior to the emergence of clinical symptoms.       Finally, the development over the last decade of extremely rapid-acting (within 24 hours) medications such as low-dose ketamine for treatment resistant mood disorders have significant potential along with the intense study of their relevant mechanisms of action could identify drug targets for even more effective treatments.

June 14, 2018