The New Techniques Driving Psychiatric Research

Advanced molecular techniques provide new insights into psychiatric illness.

9/22/2021 12:19:00 AM

To understand psychiatric illnesses such as depression and schizophrenia, scientists are beginning to study the genes found in human brains. Here's what they're finding.

Advanced molecular techniques provide new insights into psychiatric illness.

of a cell, how it functions, and how it interacts with other cells. By studying the mRNA from tens of thousands of nuclei in the brains of people with major depressive disorder and comparing it to people without the illness, you can learn how the brain cells are functioning and interacting differently.

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Nagy and her colleagues published their findings using single nucleus RNA sequencing in 2020 in the journalNatureNeuroscience. In males with major depressive disorder, they found the majority of mRNA differences in two types of brain cells: oligodendrocyte precursor cells and deep layer excitatory neurons. Oligodendrocyte precursor cells, or OPCs, are so named because they are the cellular precursors to oligodendrocytes (the cells in the brain and spinal cord that generate myelin).

But, as Nagy and her colleagues point out in their 2020 paper,"OPCs are now thought to be a distinct [brain cell] type" with roles independent of their precursor function. They contribute to brain plasticity, for example. Excitatory neurons increase the likelihood of other neurons generating action potentials (the little bursts of electrical activity that serve as information currency in the brain). mRNA changes in OPCs and the excitatory neurons allowed the researchers to link the functioning of the two cell types. This link provides insight into how they interact with one another and how this changes with major depression.

Dr. Andrew Jaffe is an associate professor in the Departments of Mental Health, Biostatistics, Psychiatry and Behavioural Sciences, Neuroscience, and HumanGeneticsat John Hopkins University. Jaffe also studies mRNA changes in the brains of the deceased, but in a slightly different way. Spatial transcriptomics is a technique that allows you to measure mRNA in a way that preserves information about the precise location of where the mRNA came from.

THE BASICSFind a therapist near meWhere a brain cell is located is related to its function. An OPC in the white matter tracts of the spinal cord may behave much differently than an OPC in the cerebellum, for example. Location is especially important in brain regions like the cortex, which has layers. Brain cells in each layer function differently, look different, work differently and connect differently.

Jaffe and his colleagues studied spatial mRNA changes in the six-layered human dorsolateral prefrontal cortex. The results were published in Nature Neuroscience in 2021. By integrating their spatial transcriptomic data with previously collected data about gene changes in psychiatric disorders, they localized genes implicated in schizophrenia and autism spectrum disorder to specific layers of the cortex.

Read more: Psychology Today »

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so you can use genes to work out autism mis diagnosis so therefore mis diagnosed mental health issues and vice versa?

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