Molecular similarities in gene expression between autism and schizophrenia and other psych disorders
By Dr. Alan Kadish NMD
With the explosion in genetics coupled with great new big data tools, many correlations between genes and diseases are being found daily. Did you know that ~1 in 5 people in the US suffer from some form of mental disorder ? (2016 data NIMH)
Psychiatry has been literally the last “try it and see what happens” area of medicine for way too long. Treatment of symptoms is the hallmark of this arm of medicine. Curiously urinary neurochemicals can be easily tested however, even this set of functional evaluations is often overlooked. There is an active number of laboratories doing these tests for years now and the technology is well established.
The publication, “Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap” took a look at >700 samples of brains from deceased subjects. The intent was to look at the tissues samples and compare the genetics and chemical expression similarities between different psychiatric patients vs. normal patients. They were looking for both similarities and any unique patterns for the individual disorders.
With this meta study the UCLA team reviewed many molecular and genetic brain publications. They focused on 5 types of psychiatric patients: autism, schizophrenia, bipolar disorder, depression, and alcoholism. The initial work by many researchers was regarding the similarities between the 5 brain disorders, but focused on the areas of the brain affected. The current work is evaluating the genetic and molecular expressions, along with what cells types might be involved.
In this study the researchers analyzed gene expression patterns done by other researchers. Unlike previous studies which looked at the DNA of psychiatric patients, such as the global Psychiatric Genomics Consortium study, they found that people with autism, schizophrenia, bipolar disorder, depression, and alcoholism frequently share known DNA variations and chemical expressions.
Schizophrenia and Bipolar Disorder
Work by Karen Faith in 2013 evaluated the noted gene and expression changes in multiple brain tissues of patients who had suffered with schizophrenia and affective disorders. She and her collegues highlighted the findings of specific gene modifications and expression similarities within the population with schizophrenic and mood disorders. They only had ten ASD identified samples.
Typically these disorders are considered very different in their expression although similar classes of medications are used for both, suggesting similar chemical communication.
The lead researcher of a Science publication, Daniel H. Geschwind, M.D., Ph.D. is well know in the field and is the director for the Center for Autism Research and Treatment (CART), at UCLA. He provides scientific oversight for the Autism Genetic Resource Exchange (AGRE), a gene bank housing data and biomaterials from over 2000 AGRE families, most of whom have two or more children on the autism spectrum
Additional findings from the study include, neuronal firing influencing and regulating genes some of which were down regulated (reduced expression) in autism, along with those patients with schizophrenia and bipolar disorder. Commonality of the brain cell communication chemical alterations plays a role in all three conditions. The researchers concluded that “These results suggest convergence of common and rare genetic variation acting to down-regulate synaptic function in ASD and SCZ.” (Basically the nerves fail to send the signals as robustly as normal)
Another unique finding was genes specifically related to microglial cells, (the immune defense system cells of our central nervous system) were over working and specific to autistic brain samples. It’s theorized their over expression might play a role in autism’s symptoms. This finding correlates with the studies into the pruning of brain neurons during our early maturation that seemingly has gone astray in ASD brains. This seems coupled with various other immune dysfunctions, seen commonly in ASD patients.
The researchers concluded that , “Results fit with convergent evidence for microglial up-regulation in ASD and an emerging understanding that microglia play a critical role regulating synaptic function during neurodevelopment “.
Meanwhile, genes linked to neuronal firing was down regulated (reduced) in autism, as well as in schizophrenia and bipolar disorder—suggesting that changes in brain cell communication play a role in all three conditions.
*There are multiple similarities between different disorders, both in terms of genetics and chemical expressions.
*We are only starting to understand the complexity of the brain disorders.
*More research is needed to appreciate the complexity of the brain
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