Most psychiatrists believe that depression is caused by low levels of monoamines, such as serotonin, norepinephrine, and dopamine.
The first antidepressants were known as the tricyclics, but they’ve since been replaced by antidepressant medications, such as the selective serotonin reuptake inhibitors (SSRIs).
SSRIs have improved safety and side-effect profiles. They boost the levels of serotonin (one of the monoamines) in the brain.
However, a 2014 study suggests that there are at least five biotypes of clinical depression.
William J. Walsh, PhD, president of the Walsh Research Institute, and his team looked at 320,000 blood and urine chemistry test results and 230,000 medical history factors from approximately 2,800 patients diagnosed with depression.
They found that five major depression biotypes represented about 95 percent of the patients.
Upon close examination, Walsh and his team discovered that three of these forms of depression are not caused by fluctuating serotonin levels.
Here are the five types of depression Walsh and his team outlined.
This type of depression was found in 38 percent of patients in the study. The underlying concern in these cases is low activity at serotonin receptors, apparently due to rapid reabsorption after serotonin is released into a synapse.
“It’s not serotonin deficiency, but an inability to keep serotonin in the synapse long enough. “Most of these patients report excellent response to SSRI antidepressants, although they may experience nasty side effects,” Walsh said.
This type of depression was found in 15 percent of the patients studied. Most of these patients also said that SSRI antidepressants helped them. These patients exhibited a combination of impaired serotonin production and extreme oxidative stress.
Accounting for 17 percent of cases in the study, these patients cannot properly metabolize metals. Most of the patients said that SSRIs do not have much of an effect — positive or negative — on them.
However, they reported benefits from normalizing their copper levels through nutrient therapy. Most of the patients were women who were also estrogen-intolerant.
“For them, it’s not a serotonin issue, but extreme blood and brain levels of copper that result in dopamine deficiency and norepinephrine overload,” Walsh explained. “This may be the primary cause of postpartum depression.”
These patients account for 20 percent of the cases studied. Many of them said that SSRIs worsened their symptoms, while folic acid and vitamin B-12 supplements helped. Benzodiazepine medications may also help people with low-folate depression.
Walsh said that a study of 50 school shootings over the past five decades showed that most shooters probably had this type of depression, as SSRIs can cause suicidal or homicidal ideation in these patients.
This type of depression is caused by toxic-metal overload, usually lead poisoning. Over the years, this type accounted for 5 percent of depressed patients, but removing lead from gasoline and paint has lowered the frequency of these cases.
“We are not the first to suggest that there may be other causes of depression, but we might be the first to identify the other forms of depression and the first to suggest blood testing to guide the treatment approach,” Walsh said.
Diagnosing depression with blood and urine tests
A urine test can detect pyrrole depression, while blood testing can identify the other biotypes.
Walsh said a physician-training program is in place to expand the testing throughout the world.
Last month, 66 doctors from Australia were trained in the approach, and training for U.S. physicians will take place in October. Walsh's goal is to educate 1,000 doctors on this issue in five years.
“Psychiatrists appear to be the most enthusiastic participants,” he said.
David Brendel, MD, PhD, a Boston-area psychiatrist, said it would be a “significant advance” to diagnose treatable forms of depression with objective medical tests.
“But I don't see adequate evidence that these (or other) researchers are anywhere near accomplishing this,” he said. Brendel added that depression likely has many causes and complex neurophysiological underpinnings.
He said the medical community is still “entirely unable” to diagnose it using medical tests, though he said researchers may be closer to having tests, such as gene assays, that can identify the most effective medical treatment for a specific patient.
Mona Shattell, PhD, RN, FAAN, professor and department chair of the Department of Community, Systems and Mental Health Nursing, College of Nursing at Rush University in Chicago, said that being able to diagnose depression with a blood test could potentially increase the number of people diagnosed and lead to more people being treated for the condition.
“It would also be helpful because depression, and other mental illnesses, are still stigmatizing,” she said.
“If depression could be detected via a blood test, it would clearly be in the realm of ‘medical illness’ and therefore a ‘real’ problem that is not due to individual weakness or other equally stigmatizing reasons.”
Editor’s note: This piece was originally reported on May 8, 2014. Its current publication date reflects an update, which includes a medical review by Timothy J. Legg, PhD, PsyD, CRNP, ACRN, CPH.