The ability to generate accurate maps of brain metabolism, while scientifically interesting, is of little use to medicine unless those maps help answer clinical questions which cannot be otherwise answered. One important test-case is mood disorders.  Major Depressive Disorder, also called unipolar depression, treated with antidepressants, and Bipolar Disorder, treated with mood stabilizers, both feature depressive episodes which are clinically identical.  Furthermore, many cases of bipolar disorder begin with a depressive episode, particularly in females.

Even though 1-2% of the population struggles with bipolar disorder, it is not actually known how often an initial depressive episode is the beginning of a unipolar or a bipolar disorder.  The consequences of misdiagnosis can be severe.  If individuals with bipolar disorder are treated with standard antidepressants, this can trigger sudden mood instability with a switch into either mania, or a mixed mood state, which is a simultaneous combination of manic and depressive symptoms, with a risk for suicide attempts approaching 20%.  Or, sometimes, individuals with bipolar depression simply get worsening of their depression with antidepressants, so other antidepressants are tried.  If someone does not respond to three adequate antidepressant trials, they are diagnosed with “Treatment Resistant Depression,” with numerous treatment and investigation protocols employed.  

The upshot of all this is, mistreatment of bipolar depression with antidepressants can lead to years of diagnostic delay and even greater misery than if the individual simply went untreated.  So, in the real world, beyond scientific curiosity for its own sake, the potential impact of diagnostic clarification is hard to overstate.

Given the markedly different response to antidepressants of unipolar depression from bipolar depression, it is reasonable to wonder if these two conditions, while looking the same on the surface, are driven by different neurobiological pathways.  If we want to understand neurobiology, we need to turn to tools which examine brain function. My own interest in perfusion SPECT is the opportunity it gives us to look “under the hood” of psychiatric distress.

What do we find when we examine the brain activity patterns of unipolar depression compared with bipolar depression?  One of the more consistent markers is left vs right hemisphere differences in activity.  Unipolar depression seems to be linked with less activity in the right frontal lobe, while bipolar depression appears more commonly linked with less activity in the left, when compared to healthy controls.  To date, however, numbers of subjects in research studies are very small, and the findings have not been consistently replicated. We need research in very large sample sets to establish the confidence.  

This is precisely where we have turned our attention, and we are eager to explore the Amen data in pursuit of answers.

Dr. Rob Tarzwell, MD, FRCPC (Psychiatry, Nuclear Medicine)

Clinical Assistant Professor, Faculty of Medicine, UBC


Prevalence of Major Depression Among Adults:

Prevalence of Bipolar Disorder Among Adults:

Clinical Guidelines for the Management of Major Depressive Disorder in Adults:

Clinical Guidelines for the Management of Patients with Bipolar Disorder:

Distinctions Between Bipolar and Unipolar Depression:

SPECT Study of Regional Cerebral Blood Flow in Bipolar Disorder:

Unipolar and Bipolar Depression – Different or the Same?

Unrecognized Bipolar Disorder in Primary Care Patients With Depression: