Scientists have discovered that there is a tremendous amount of overlap between autism, depression, and other mental disorders.
In a potentially groundbreaking new discovery that could lead to better diagnoses and treatments, scientists have determined that a variety of mental disorders such as autism, schizophrenia, and depression are linked by genetics, and may be more common than thought. These disorders are different from brain diseases like Alzheimers, which cause physical changes to the brain, and as a result can be harder to detect.
Scientists were able to use genetic analysis to find patterns in gene expressions in different individuals with mental disorders. They did this by measuring the RNA in 700 tissue samples from people who had disorders like autism or bipolar disorders and even alcoholism, and compared it to groups of people who did not.
They found that gene expressions were similar across mental disorders, and were able to spot patterns shared between the groups. It is an important discovery with major implications in the medical community.
The abstract from the paper follows below.
Many genome-wide studies have examined genes associated with a range of neuropsychiatric disorders. However, the degree to which the genetic underpinnings of these diseases differ or overlap is unknown. Gandal et al. performed meta-analyses of transcriptomic studies covering five major psychiatric disorders and compared cases and controls to identify coexpressed gene modules. From this, they found that some psychiatric disorders share global gene expression patterns. This overlap in polygenic traits in neuropsychiatric disorders may allow for better diagnosis and treatment.
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, and alcoholism—compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism–based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.
The full statement from the University of California Los Angeles follows below.
Most medical disorders have well-defined physical characteristics seen in tissues, organs and bodily fluids. Psychiatric disorders, in contrast, are not defined by such pathology, but rather by behavior.
A UCLA-led study, appearing Feb. 9 in Science, has found that autism, schizophrenia and bipolar disorder share some physical characteristics at the molecular level, specifically, patterns of gene expression in the brain. Researchers also pinpointed important differences in these disorders’ gene expression.
“These findings provide a molecular, pathological signature of these disorders, which is a large step forward,” said senior author Daniel Geschwind, a distinguished professor of neurology, psychiatry and human genetics and director of the UCLA Center for Autism Research and Treatment. “The major challenge now is to understand how these changes arose.”
Researchers know that certain variations in genetic material put people at risk for psychiatric disorders, but DNA alone doesn’t tell the whole story. Every cell in the body contains the same DNA; RNA molecules, on the other hand, play a role in gene expression in different parts of the body, by “reading” the instructions contained within DNA.
Geschwind and the study’s lead author, Michael Gandal, reasoned that taking a close look at the RNA in human brain tissue would provide a molecular profile of these psychiatric disorders. Gandal is an assistant professor of psychiatry and biobehavioral sciences at UCLA.
Researchers analyzed the RNA in 700 tissue samples from the brains of deceased subjects who had autism, schizophrenia, bipolar disorder, major depressive disorder or alcohol abuse disorder, comparing them to samples from brains without psychiatric disorders.
The molecular pathology showed significant overlap between distinct disorders, such as autism and schizophrenia, but also specificity, with major depression showing molecular changes not seen in the other disorders.
“We show that these molecular changes in the brain are connected to underlying genetic causes, but we don’t yet understand the mechanisms by which these genetic factors would lead to these changes,” Geschwind said. “So, although now we have some understanding of causes, and this new work shows the consequences, we now have to understand the mechanisms by which this comes about, so as to develop the ability to change these outcomes.”
In addition to Geschwind and Gandal, the study’s authors are Jillian Haney, Neelroop Parikshak, Virpi Leppa, Gokul Ramaswami, Chris Hartl and Steve Horvath, all of UCLA; Andrew Schork, Vivek Appadurai, Alfonso Buil and Thomas Werge, all of the Institute of Biological Psychiatry, Mental Health Services Copenhagen in Denmark; Chunyu Liu of the University of Illinois at Chicago; Kevin White of the University of Chicago; the CommonMind Consortium; the PsychENCODE Consortium; and the iPSYCH-BROAD Working Group.
The study was supported with funding from the National Institute of Mental Health, the Simons Foundation Autism Research Initiative and the Stephen R. Mallory schizophrenia research award at UCLA.
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