Stem cell research reveals path to schizophrenia

3d illustration of brain nerve cells – Photo courtesy Science Photo

If you don’t know what’s causing a problem it’s hard to come up with a good way to fix it. Mental health is the perfect example. With a physical illness you can see what the problem is, through blood tests or x-rays, and develop a plan to tackle it. But with the brain, that’s a lot harder. You can’t autopsy a brain while someone is alive, they tend to object, so you often only see the results of a neurological illness when they’re dead.

And, says Consuelo Walss-Bass, PhD, a researcher at the University of Texas Health Science Center at Houston (UTHealth), with mental illness it’s even more complicated.

“Mental health research has lagged behind because we don’t know what is happening biologically. We are diagnosing people based on what they are telling us. Even postmortem, the brain tissue in mental health disorders looks perfectly fine. In Alzheimer’s disease, you can see a difference compared to controls. But not in psychiatric disorders.”

So Wals-Bass and her team came up with a way to see what was going on inside the brain of someone with schizophrenia, in real time, to try and understand what puts someone at increased risk of the disorder.

In the study, published in the journal Neuropsychopharmacology, the researchers took blood samples from a family with a high incidence of schizophrenia. Then, using the iPSC method, they turned those cells into brain neurons and compared them to the neurons of individuals with no family history of schizophrenia. In effect, they did a virtual brain biopsy.

By doing this they were able to identify five genes that had previously been linked to a potential higher risk of schizophrenia and then narrow that down further, highlighting one gene called SGK1 which blocked an important signalling pathway in the brain.

In a news release, Walss-Bass says this findings could have important implications in treating patients.

“There is a new antipsychotic that just received approval from the Food and Drug Administration that directly targets the pathway we identified as dysregulated in neurons from the patients, and several other antipsychotics also target this pathway. This could help pinpoint who may respond better to treatments.”

Finding the right treatment for individual patients is essential in helping them keep their condition under control. A study in the medical journal Lancet estimated that six months after first being prescribed common antipsychotic medication, as many as 50% of patients are either taking the drugs haphazardly or not at all. That’s because they often come with unpleasant side effects such as weight gain, drowsiness and a kind of restless anxiety.

By identifying people who have specific gene pathways linked to schizophrenia could help us better tailor medications to those who will benefit most by them.

One thought on “Stem cell research reveals path to schizophrenia

  1. Stem cells require growth factors to grow and differential into more mature state of cells. They change their phenotype and genetic network during the progression from a less to a more differentiated state. Thus, growth factors responses by the adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes throughout life. The alterations of gene may produce abnormal cells with impairment of the function.

    Psychiatric illnesses are related to cellular impairment of the function for survival or death in neurons which may consequently appear as abnormalities in neuroplasticity. Through transducing cell surviving signal, the PI3K/AKT/GSK3 pathway may organize an intracellular central network for the action of synaptic neuroplasticity. In addition, the pathways may also regulate cell proliferation, cell migration and apoptosis. Many evidence supported a role for this signaling network underlying the development and treatment for psychiatric illnesses. Recently, study with hiPSC technology, blood cells were reprogrammed into stem cells and then proceeded to become brain neurons. Among the differentially expressed genes, five of them have been identified as schizophrenia candidate gene. However, SGK1 is an only gene associated with PI3K/GSK3 pathway. The alterations of gene is closely linked to a higher risk of developing schizophrenia.

    Stem cells are multipotent cells to give rise to a much larger population of more developmentally restricted progenitor cells. The progenitors require many stages of differentiation to develop into mature and functioning cells. During the process of maturation, the response to specific growth factors from one precusor cells may change accordingly to other type of growth factor in the more mature cells. This reflects a differentiation-linked change in either the constituents or the ultimate targets of signal transduction network. Therefore, growth factors play pivotal roles to regulate phenotype, gene expression and functioning cells. The study of brain organoids to determine the genes involved in pathological illnesses of brain is inconclusive. In fact, the brain organoids have been considered as early stage of developmental cells which are immature and lack of functioning. Whereas, mature cells are active, adherence and fully function with complicated of genetic network. The determination of key genes in mature cell type play major roles to cause pathological conditions of schizophrenia is critical to reveal an important insight for developing an effective therapeutic treatment for psychiatric illnesses.

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