Coming Someday in Your Intermediate Future: Brain Scans as a Diagnostic Tool in Bipolar
What if a doctor could get our diagnosis right the first time, just from reading a brain scan? In theory, the technology exists. The catch is we’re not quite sure what we are looking for.
Mary Phillips directs brain imaging research into depression and bipolar at the University of Pittsburgh and Cardiff University. A 2007 review article she published (with Matthew Keener), Neuroimaging in Bipolar Disorder: A Critical Review of Current Findings, is still fresh. Here is what we are dealing with:
“Phenotype” refers to the observable part of our illness, all those symptoms that psychiatry ties into a bundle and stamps with a DSM seal of approval. In the context of bipolar, this refers to our “state.” State is all about the here and now. Tomorrow may tell an entirely different story.
Below the surface we have the world of “endophenotype,” which does not exactly correspond with the world of phenotype. Here, we are looking for “trait,” which implies a sense of permanence. We are on a mission for tell-tale biomarkers that that indicate chronic difficulties in the brain’s ability to process thoughts and emotions.
Over the years, the focus of brain research has shifted from “structural” to “functional.” When I attended my first International Conference on Bipolar Disorder in 2001, just about all the brain scan studies at the poster sessions there dealt with suspect structural abnormalities. This had to do with whether this or that part of the brain seemed larger or smaller than it appeared in “healthy” individuals. By 2007, the studies were all about what the brain actually did and how the various parts connected.
In other words, if you put bipolar subjects into a brain scan machine (not at the same time) and exposed them to certain stimuli or made them perform basic cognitive tasks, would their brains light up differently than “healthy” subjects?
Obviously, in a manic or depressed “state,” you would see a difference. But what about when the subject is symptom-free? One of the first such brain scan studies I reported on (about 10 or 11 years ago) found that bipolar subjects, even in a state of wellness, had to work certain areas in their prefrontal cortices a lot harder than control subjects when having to sort out conflicting inputs in a hurry. (This involved performing the Stroop Task, where one needs to correctly identify say the word “blue” spelled in red text.)
Fast forward to 2013. In a study published in May in the American Journal of Psychiatry, Dr Phillips and her colleagues reported on what may be different about the way those with bipolar process “response to reward.” Response to reward is not exactly something you will find on a DSM symptom list. But according to Dr Phillips, bipolar “may be conceptualized as a spectrum of disorders in which reward hypersensitivity is a key dimension of pathology.” This, in turn, may underlie a predisposition to mania, hypomania, and mood dysregulation.
The ventral striatum, in the midbrain, is believed to play a major role in the brain’s reward system. Previous studies have shown increased ventral striatum activity in bipolar subjects when given reward-based tasks compared to control subjects.
In this study, euthymic bipolar I and bipolar II patients, along with healthy controls, played a card guessing game involving a monetary reward. The trial included an “anticipation phase,” with participants awaiting the outcome of their guess, followed by the actual outcome. The surprise in this study was that the bipolar II subjects showed greater ventral striatum activity than those with bipolar I.
According to Dr Phillips et al, this type of activity “may be a biomarker of bipolar II disorder, as previously shown for bipolar I disorder.”
Here’s the intriguing part: Perhaps tests like these “could ultimately be used to help discriminate bipolar from unipolar depressed patients.”
I had to reread that part several times to make sure I got it right. Bipolar depression is notoriously difficult to distinguish from unipolar depression. On encountering patients in a depressed “state,” clinicians invariably get it wrong. I’ve been there. You’ve been there. But suppose by looking at a brain scan, a trained clinician could truly identify unambiguous biomarkers - those permanent underlying traits - and make the correct diagnostic call. The first time. Not ten years later. We are a long long way away from this happening. But the possibilities - can you imagine?