Important New Observations Regarding Correlations Between Volume Changes Within a Specific Structure of the Brain and Major Depressive Disorder and Bipolar 1 Disorder

Posted in: Clinical Trials

Recently, an article published by a team of scientists headed by Dr. B. Cao out of the University of Texas Health Science Center in Houston claims to be among the first to provide empirical evidence of specific volumetric changes within a structure in the brain known as the hippocampus and bipolar 1 disorder (B. Cao et al., Hippocampal Subfield Volumes in Mood Disorders (Molecular Psychiatry, January 24, 2017, doi: 10.1038/mp.2016.262. [Epub ahead of print]).

The hippocampus is actually a pair of structures – located bilaterally on each side of the brainin the general area of our temples.  The hippocampi are fairly large, highly complex structures made up of a number of distinct, clearly identifiable subfields.

As with many important findings in science, the first glimmer about the function and importance of the hippocampus was initially found by accident. A patient, HM, presented with extremely frequent and highly debilitating grand mal seizures.  It was thought at the time (the mid 1950’s) that the hippocampus had no discernable function and that the patient would suffer no significant harm from their removal.  That any learned physician could conclude that as large a structure within the brain as the hippocampus would have no function is, in itself, mind boggling.  Nonetheless, they were removed.  The surgery was indeed successful in eliminating HM’s seizures.  Unexpectedly, however, it left him with an inability from that point until his death many years later with an inability to learn or remember more than a small handful of new bits of information.  He lived essentially in a state of constant present.  Distract or shift his attention only slightly, and he completely forgot what was being asked of him or what he was doing previously.  Since that time, HM has been the focus of intense research into the role the hippocampus plays in the processes underlying learning and memory.

It comes, therefore, as a bit of a surprise that new emerging evidence would suggest that the hippocampus would also be implicated in something other than learning and memory.  For example, it has been known for a number of years that the hippocampal volume is decreased in patients suffering from major depressive disorder (MDD).  With the advent of magnetic resonance imaging (MRI) it has been possible to visualize and measure where the changes actually occur within the hippocampus.  Importantly, the decrease in volume was not found to be homogeneous, but localized to specific subfields. The conclusion that is emerging is that “different subfields of the hippocampus may respond to stress and may also have differential levels of plasticity (ability to change) in response to antidepressant treatment” (Malykin and Coupland, Neuroscience, 309:200-213, 2015).

The above observations have now been further advanced by Cao et. al. with respect to bipolar 1 disorder.  They found measurable differences in the volume of a number of specific subfields within the hippocampus of patients suffering from not only MDD,but also bipolar disorder compared to healthy subjects.  “The volume reductions were especially severe in the patients suffering from bipolar 1 disorder, and correlated with the progression of the illness.” Furthermore, the reductions in hippocampal subfield volumes were found to be “negatively correlated with the number of manic episodes” that were experienced by these patients.

Clearly, more studies need to be conducted to further elucidate how changes within the hippocampus are related to MDD and bipolar-1 depression (or mood disorders, in general). Findings fromthis line of research will then, hopefully, point the way toward the development of new pharmacological approaches to the treatment of mood disorders.  For the time being, however, it is important to know that there are a number of clinical research studies being conducted within the New York City Metropolitan Area that are trying to identify more effective, reliable and safer treatments to MDD and bipolar 1 disorder.  To find out where such studies are being conducted in your area, and/or to learn if you or someone you know might benefit from participating in one of these ongoing clinical research studies, consider searching the web using such keywords as Depression Research Studies New York City or Bipolar Disorder Research Studies New York City.

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