Double trouble "Your brain pays a price for the violent cycling—it's scarred by it," says Malhi (right), with Lagopoulos
Many people would feel a lot better about psychiatry were there definitive tests for its catalog of disorders. For now, its practitioners make judgments on the basis of checklists and observation — solid methodology as far as it goes, but not the same as, say, a blood test for anaemia or an x-ray of a broken femur. In the search for a test offering this kind of diagnostic certainty in mental illness, two Australian researchers believe they've made a leap. Gin Malhi and Jim Lagopoulos, from the department of psychological medicine at Sydney's Royal North Shore Hospital, report detecting what appear to be abnormalities in the workings of the brain of people with bipolar disorder — a finding, they say, that could eventually allow doctors to subdue the condition before it can wreck patients' lives.
Thought to strike about 1% of adults, bipolar can look a lot like depression even to the trained eye. Though it's defined by almighty shifts in mood—from sad and hopeless to mania, in which irrational thoughts and impulses run amok — bipolar sufferers tend to spend much more time in an emotional black hole and may consult a doctor before they've experienced a high. In these cases, a misdiagnosis of depression happens a lot, says Malhi, and that's a problem because bipolar is "a totally different condition" requiring different treatment.
The imaging study, to be published shortly in the American journal Bipolar Disorders, is the culmination of four years' work by a psychiatrist (Malhi) and a neuroscientist (Lagopoulos) who make an engagingly odd pairing. Cambridge-trained Malhi does most of the talking, often employing metaphors to explain complex ideas; Lagopoulos pipes up in a manner that suggests he would have impressed the heck out of his high-school science teacher. They often disagree, and sometimes argue "but outside work we're the best of friends," says Lagopoulos.
The pair knew from their previous research that, presented with certain stimuli, depressed bipolar patients don't use the prefrontal (or higher thinking) part of their brain as much as healthy subjects do, instead recruiting other (more hardwired) parts to compensate. And they found a similar pattern of activation in patients at the manic end of the spectrum. This was tantalizing because it suggested the disparities were related not to mood but to bipolar itself. Needing more evidence, they began studying bipolar patients in the euthymic state — when their moods have stabilized and they appear to be well. The results continued to suggest that they were on to something.
In their latest study, Malhi and Lagopoulos used functional magnetic resonance imaging to see what happens in the normalized bipolar brain when subjects are asked to interpret facial expressions—specifically, of fear and disgust. While reading faces is something bipolar patients often feel they're struggling with, the study showed that the 10 patients' interpretations were as accurate and speedy as the 10 controls'. Crucially, however, their method of processing was different.
Shown faces expressing fear, the healthy brains lit up predictably in the lozenge-shaped amygdala, an emotional center involved in recognizing expressions and tones of voice. But with the patients, the same images caused less activation of the amygdala and more of several other areas including the hippocampus, which encodes and retrieves memories. "Instead of processing a particular face in the context of right now, the brain is basically going back into its filing cabinet and picking out previous experiences, which is not an efficient way for it to work," says Malhi, chair of psychological medicine at the University of Sydney. While patients' brains over-activated in response to fear, they under-activated for disgust. The researchers believe that what they've found in these impairments is a biological marker of bipolar disorder that could be the makings of a test. "We're excited about this because the potential is huge," says Lagopoulos, "but we have to temper our enthusiasm" until further research can confirm these differences as statistically bullet-proof.
Possible objections include the perennial doubt about whether what we're seeing in these types of studies is illness pathology or an effect of drug treatment. And is there a chance that sufferers of straight (unipolar) depression might show the same processing irregularities as bipolar patients? Which would be the death knell of a test purported to separate the two. Malhi and Lagopoulos doubt this would be the case — the two types of depression are quite different, they say—but Malhi adds: "No study has directly compared the two groups... and this would be the ideal experiment." For Malhi and Lagopoulos, it's a reminder that the deeper we delve into the mysteries of the brain, the more there is to learn.
