A blood test using RNA markers is offering new hope to people with mood disorders such as depression in what could be a significant breakthrough in the diagnosis of mental health conditions.
A team from the US’s Indiana University School of Medicine launched the blood test in April, claiming it to be psychiatry’s first-ever biological answer to diagnosing a mood disorder.
“This avoids years of trials and error, hospitalisations, and side-effects. As these are very common disorders, we think we can do a lot of good with this and other tests and apps we have developed.The study delved into the biological basis of mood disorders, developing a tool to distinguish which type of mood disorder a person has – depression or bipolar disorder.
To develop the test, Dr Niculescu’s team drew on its 15 years of previous research into how psychiatry relates to blood gene expression biomarkers – measurable indicators of a biological state in the form of RNA, DNA, proteins or other molecules.
Every system in the body – the brain, the nervous system, the immune system – has a common developmental route, says Dr Niculescu.
“For example, when you’re stressed or depressed, there are psycho-neurological mechanisms, hormones and other things that are released that affect your blood and your immune system,” he told Al Jazeera.
Conversely, an immune activation or inflammation would affect the brain.
Dr Alexander Niculescu and his team drew on 15 years of previous research to develop the test [Supplied]In the first stage of the study, the team identified a list of RNA biomarkers that could track mood states over a period of time. After validating them in an independent cohort of subjects with clinically severe depression and clinically severe mania, they finalised 26 biomarkers, which they whittled down to 12 through further testing.
With these findings, doctors would be able to send patients to a lab for bloodwork to indicate the causes of their symptoms, just as they would for a physical illness, says Dr Niculescu.
The biomarkers could also help with treatment because some of them were found to be affected by Selective Serotonin Reuptake Inhibitors (SSRIs), a class of antidepressants. Three others were identified in previous work to be affected by lithium carbonate – a mood stabiliser used in the treatment of bipolar disorder.
“Depending on which of those biomarkers are changed in [a patient], we have a list of medications … ranked by how tightly they match [the patient’s] biological profile,” Dr Niculescu said.
The blood tests developed by Dr Niculescu and his team are now available as CLIA tests for physicians to order, via a company set up by Niculescu and other experts in the field. CLIA are a set of US government standards for laboratories that test human specimens for health assessment or to diagnose, prevent, or treat disease
But according to Alexander Talkovsky, a programme officer in the Division of Translational Research at the National Institute of Mental Health (NIMH) in the United States, there is still research to be done. The key issue is whether the findings are replicated by independent researchers, he adds.
This process has been done to some extent within the study itself, says Dr Niculescu, through several steps of testing and validation in independent cohorts. According to the study, promising findings were also generated by independent large scale genetic studies released after the study was complete.
But what if the study’s premise is in itself incorrect?
Professor Ian Hickie, co-director of health and policy at the University of Sydney’s Brain and Mind Centre, and a former national mental health commissioner in Australia, argues that finding one algorithm which applies to all mood disorder patients is unlikely because the disorders are so individual and are based on clinical presentation at different stages of life.
His team is instead connecting physiology and biology to individual peoples’ symptoms, not their category of illness.
“What systems are actually perturbed? How are they represented? What are the markers of that that you can detect?” he said. “And [then] what is the combination of biological, behavioural and other treatments that corrects the situation … and then keeps you well?”
Essentially, all of these findings can be used in conjunction with clinical assessment for more accurate and conclusive diagnosis and treatment, he says.
Objective tests could transform early diagnosis
Objective testing could be of huge significance to patients going through what is currently an extremely slow process of diagnosis.
For bipolar disorder in particular, it can take years for the full array of symptoms to evolve.
Sydney psychiatrist, Dr Sonia Kumar, says that quite often bipolar disorder will first manifest itself as depression, with manic symptoms emerging later.
Other times, symptoms may be present but so low on the spectrum that diagnosis is unclear until they evolve.
If there were a biological test that could clarify these variables along with clinical assessment, says Kumar, clinicians could start accurate treatment earlier, which could mitigate a lot of suffering before it even happens.
Research associate Katrin Inci believes that an early diagnosis of her bipolar disorder could not only have saved her years of unresolved suffering, but also the severity to which her episodes escalated after diagnosis.
She was diagnosed with depression at age 13 and prescribed Zoloft, a type of antidepressant that is well known for inducing mania in bipolar patients.
“[It] spun me into a manic episode that lasted until I was 19, when I was hospitalised for the first time,” she said.
After her hospitalisation, when Inci finally received a correct diagnosis, she began what would be 10 years of trying new medications, navigating bipolar episodes and searching for wellness.
Dr Niculescu says objective tests for disorders like depression could help reduce the stigma associated with mental health conditions [Supplied]She believes that had she been diagnosed correctly at 13, her illness would not have become so severe.
Research shows that both bipolar and unipolar depression are degenerative diseases.
“If I was treated earlier … I would have had fewer episodes,” Inci told Al Jazeera. “I see it as [fewer] hospitalisations, which would have saved me tons of money and tons of time, and tons of anguish.”
An objective test for mood disorders like this blood test could also be key to reducing the stigma attached to mental health conditions, says Dr Niculescu.
“People will realise that it’s just a biological disorder … it’s not a moral weakness, you’re not lazy and so on,” he says.
Violet, a Russian model who prefers to share only her first name, has been living and working through depression for years.
She says she has internalised the stigma and often feels like a “liar”.
“Sometimes I feel like … I’m seeking attention or something,” she said. “These are things you get accused of a lot, even from people who are close to you … and then you start to wonder what if I’m actually just a selfish person who wants a lot of attention?”
Data goes a long way to dispelling this doubt, explains Kasia, a Sydney NGO worker who asked that only her first name be used.
She compares her diagnosis of depression as an adult with when she was diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) as a child.
Because tests have been created for ADHD diagnosis, she was able to see objective results for her psychiatric assessment.
“They actually showed me all my brain scans and showed me how my brain was different. That was a huge day for me, it changed everything,” she said.
Kathmandu-based psychiatrist, Dr Pawan Sharma, says that such a test could break down even more barriers to care among his patients, particularly those from more rural, isolated communities where there is low cultural awareness of mental illness.
Many of these patients are not initially aware that sadness can be an illness, says the assistant professor in the department of psychiatry at the Patan Academy of Health Sciences.
“They come [to physicians] with physical symptoms – with headaches, insomnia, loss of energy, heart palpitations – and they [are then referred] to psychiatrists,” Dr Sharma said, noting that an objective test would give patients something tangible to help explain how they are feeling.
As it stands now, says NIMH’s Talkovsky, Dr Niculescu’s study goes a long way to achieving this and moving psychiatric research forward.
“What they’re doing represents a pretty important step in our ability to create objective markers [for] mental illness,” he said.
While it is still early days, with further research, the study’s blood test may yet become a significant part of the psychiatric diagnostic toolkit, bringing clarity to diagnosis and potentially changing millions of lives for the better.
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