A simple blood test developed by neurobiologists at the University of Haifa can identify people with bipolar disorder (formerly known as manic depression) and predict the efficacy of lithium – a drug given to patients with this disorder. It’s very common, with one in every 100 adults diagnosed with it at some point in their life. It can appear at any age, but often develops between the ages of 15 and 19 and rarely after 40 years.
Bipolar disorder is a psychiatric illness that causes unusual changes in a person’s mood, energy, activity level, and concentration. These shifts can make it difficult to carry out daily tasks.
The manic phase can include feeling full of energy, self-importance, extreme happiness, excitement, or ecstasy; speak very fast; feeling full of great new ideas and big plans; easily annoyed, irritated, or agitated.
People with bipolar disorder experience dramatic mood swings that may include periods of depression and mania, but they don’t just involve mood swings. The nature and severity of these symptoms depend on the type of bipolar disorder they have. Bipolar I affects people who have had at least one manic episode in their life. While not required for a formal diagnosis, most will also experience a major depressive episode during their lifetime.
Bipolar II involves at least one hypomanic episode (a less serious form of mania) and at least one major depressive episode.
Symptoms of a manic or hypomanic episode include being easily distracted; have a reduced need for sleep, reduced need for sleep delusions or hallucinations, elevated mood; inappropriate behavior; impulsive risk behavior (including gambling and overspending); increased sexual desire; irritability, hostility, or aggression; physical agitation and non-stop movement; racing mind; and talk too much. Episodes last for at least a week. Manic episodes last at least seven days.
A hypomanic episode involves the same symptoms, but the individual’s functioning is not markedly impaired and there are no psychotic symptoms.
During depressive episodes, sufferers may cry for no reason, have prolonged periods of sadness, extreme fatigue including not wanting to get out of bed; difficulty concentrating or deciding, feelings of guilt or hopelessness, loss of interest in things that used to bring them joy; trouble sleeping or sleeping too much; no excuses or prolonged periods of grief; difficulty concentrating or being indecisive; loss of interest in health, nutrition, or physical appearance; and suicidal thoughts or urges to self-harm. There are also many physical changes such as yo-yo weight gain or loss.
The study has just been published in the prestigious journal Molecular Psychiatrywhich is part of the Nature group, with the title “Immunoglobulin genes expressed in lymphoblastoid cell lines differentiate and predict lithium response in bipolar disorder patients.”
How can you diagnose bipolar disorder with a blood test?
This test can not only diagnose bipolar in just a few days and at a relatively low cost, but can also predict the efficacy of lithium allowing psychiatrists to tailor treatment on an individual basis, explains Dr. Shani Stern from the university, who is the corresponding author of the study.
His research team includes research students Liron Mizrahi and Ashwani Choudhary of the University of Haifa’s Sagol Department of Neurobiology, in collaboration with Dalhousie University in Halifax in Canada and the Salk Institute in La Jolla, California.
Stern noted that because of the strong similarities between manic depression and other disorders such as schizophrenia, there is a risk of being misdiagnosed, at least in its early stages. There’s also no way to know in advance whether lithium will help individual patients.
The study sought to examine whether it was possible to use a blood test to identify someone with bipolar disorder and to predict the efficacy of lithium treatment for that individual. The study examined cells from three different groups in the population: people without bipolar disorder; people who have bipolar disorder and who respond to lithium treatment; and people with disorders that don’t respond to lithium.
Stern’s lab uses molecular biology combined with biophysical, electrophysiological, and numerical simulation platforms to facilitate the use of induced pluripotent stem cell technology, in which mature cells from human patients are reprogrammed into induced pluripotent stem cells. Inherited human neurons share the same genetics as the patient and are therefore an excellent model for studying diseases and disorders of the human brain. The lab focuses on bipolar disorder, Parkinson’s disease, and rare mutations that cause intellectual disability, epilepsy, and autism. By understanding the mechanisms underlying this disorder, laboratories are working to develop precise treatment programs and discover biomarkers for better diagnosis and better disease prognosis.
In the first phase of the study, isolated white blood cells from all participants were examined; cell cultures are produced that can be maintained for a long time by infecting cells with the Epstein-Barr virus (of the herpes family) which causes mononucleosis. In the second stage, the researchers extracted RNA from the cells to understand which genes were expressed in each population and to identify the differentially expressed genes.
The findings show that 80% of the difference in gene expression is related to the expression of immunoglobins, a major component of the immune system. “The most significant finding was that in people with bipolar disorder, there was a difference in the expression level of the receptor gene for antibodies; this may explain the high rate of comorbidity. There is a known correlation between various psychiatric disorders and additional morbidity,” said Stern.
After obtaining the biological findings, the researchers used an artificial intelligence-based model consisting of neural networks; AI models were developed in Stern’s lab to verify the findings. The researchers also used cells from other laboratories that executed the same biological processes as in the new study to validate that the computational model also worked for cell samples in various laboratories.
The findings of the mathematical model were able to predict with greater than 90% precision if a person had bipolar disorder and whether they would respond to lithium treatment. “This method could allow people coping with psychiatric disorders to save months of suffering by customizing the right medication for them,” Stern concluded.
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