John Hopkins Medicine researchers have released new study results on the gene, DISC1, which has been previously linked to mental health disorders such as schizophrenia and mood disorders (depression and bipolar disorder). The findings were reported online January 5th, 2010 in Molecular Psychiatry and could help doctors treat or possibly prevent certain disorders or behavioral symptoms.
This research was led by Associate Professor, Mikhail Pletnikov, M.D., Ph.D. Dr. Pletnikov discussed via email the results of this study and its possible outcomes.
Examiner: More and more children are being diagnosed with severe mood disorders. What do the studys conclusions mean as far as possible future prevention?
Dr. Pletnikov: Most mental conditions, including mood disorders, manifest themselves as a complex of varying symptoms and signs often very different from one patient to another. One of potential explanations for this heterogeneity is that even the same genetic mutation can produce diverse behavioral outcomes, depending on when the effects of that mutation took place, i.e. before birth, immediately after birth or later in life. We tested this hypothesis by evaluating brain and behavior abnormalities in genetically-modified mice in which we were able to regulate expression of mutant DISC1 (a promising psychiatric gene). So, some groups of mice had the mutation active before birth, some – after birth and the other group – during the entire life span. We found that the effects of the mutation on mouse behaviors did vary depending on when the mutation was active. Why is this so important? While we know that treatment of abnormalities that have prenatal origin will be very difficult or impossible in nearest future, identification of symptoms and diseases features that are associated with postnatal effects will help us aim at them since they are likely to be treatable or even preventable in children before those symptoms will appear later in life.
Examiner: How can these results be used to develop new treatment methods?
Dr. Pletnikov: Our approach should help us find new targets for treatments. By regulating expression of bad genes in our model, we hope to learn what outcomes can be targeted long before behavioral disorders are present. In addition, our approach will help us to detect permanent and reversible abnormalities. So, if we knew what symptoms are reversible, we would be better off designing drugs aimed at those plastic targets.
Examiner: What further studies are being planned and what is the hoped for results of those studies?
Dr. Pletnikov: We are planning to identify more accurate time windows for specific brain and behavior abnormalities in DISC1 mice. We also plan on starting new treatment experiments to target abnormalities that seem to be related to postnatal expression of mutant DISC1 with a hope that these abnormalities will be most amenable targets for therapeutics.