Depression and bipolar disorder can both cause people to go through periods of extreme sadness and despair, and even mental health experts may find it difficult to distinguish between the two disorders. But new research suggests these conditions may have very different patterns of brain activity.

In a new study, researchers scanned the brains of people with clinical depression and other people with bipolar disorder, and measured these individuals' reactions to emotional photographs. The researchers found differences in the amount of activity in brain areas involved in regulating emotion in bipolar patients, compared with patients who had "unipolar" depression (a term used to distinguish the condition from bipolar disorder).

"As psychiatrists, we have a big problem: We cannot distinguish unipolar depression from bipolar depression," said Dr. Eric Ruhe, a psychiatrist at the University of Amsterdam in the Netherlands. This inability to tell which disorder a patient has is a problem because antidepressant medication usually isn't effective for treating people with bipolar disorder, he said. Such medicines can even increase such a patient's risk of having a manic episode, he said. During manic episodes, a person with bipolar disorder may become agitated, euphoric and sometimes psychotic. [Top 10 Stigmatized Health Disorders]

The new findings could lead to a better way of diagnosing and treating patients with these disorders, according to the study, published today (May 6) in the journal JAMA Psychiatry.

People with either depression or bipolar disorder may have bouts of severe depression and difficulty regulating their emotions, whether they are happy or sad. But unlike people with depression, those with bipolar disorder also experience manic episodes, during which they can be very destructive. During these episodes, the individuals may have affairs, sell everything they own or buy things they can't afford. In the new study, Ruhe and his colleagues searched for a better way to distinguish between people with each disorder. They looked at 42 patients with depression, 35 with bipolar disorder and 36 individuals with neither disorder.

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The researchers scanned the participants' brains using functional magnetic resonance imaging while testing the participants' ability to regulate their emotions. Researchers did this by showing photos of people depicting different emotions (sad, happy, fearful and neutral). For example, a sad photo might show a person overdosing on pills, whereas a happy photo might depict a person skiing. The researchers instructed the participants to either passively experience the images or actively regulate their emotions by distancing themselves from what they were seeing, for example, by reminding themselves, "this is only a picture." The participants rated how strongly they felt after looking at each image. Researchers measured the individuals' ability to regulate their emotions by subtracting the rating of the passively viewed photos from the rating reported after the participants had actively distanced themselves from the images.

Unlike previous experiments, this one was conducted both while patients were in a normal state of mind and while they were in a depressed state, and none of the participants were taking psychiatric medication.

The behavioral data revealed that when the participants were feeling normal (not depressed), those with bipolar disorder were much worse at regulating both happy and sad emotions than those with depression. But when they were feeling depressed, the bipolar patients were actually better at regulating happy emotions. Both groups performed about the same when trying to regulate sad emotions while depressed.

The differences in brain activity between the two types of patients were striking, the researchers said in their study. In a nondepressed state, the bipolar patients showed increased brain activity (compared with the depressed patients) in a region called the dorsolateral prefrontal cortex, which is involved in actively regulating emotions. This suggests bipolar patients' brains had to work harder than those of the depressed patients to achieve the same level of emotional control, Ruhe said.

By contrast, in a depressed state, the bipolar patients showed decreased brain activity (compared with the depressed patients) in the rostral anterior cingulate cortex, which acts as a hub connecting the cognitive and emotional parts of the brain.

So even though both the bipolar and depressed patients showed no behavioral difference in controlling their sadness during bouts of depression, their brain activity revealed a big difference, Ruhe said.

Next, it will be important to study whether the differences in brain activity that the researchers observed in the study can be used to differentiate between patients with these two disorders, the researchers said.

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