Medications taken by people with bipolar disorder may actually be nudging
hundreds of genes that direct the brain to behave more normally, according to
The study suggests that anti-psychotic drugs activate a wide range of genes,
changing their function, said lead author Dr Melvin McInnis.
"A gene's activity in any given cell will vary depending on what it's exposed
to," said McInnis, a professor of bipolar disorder and depression at the School
of Medicine at the University of Michigan.
It's not often that scientists stumble upon something in research that they
totally weren't expecting to see. "It was a major surprise to us that people
treated with an anti-psychotic [medication] had changes in the gene expression
pattern," McInnis said.
The findings could help point the way to new gene-targeted and stem cell
therapies, and provide valuable insight into what causes manic-depressive mood
swings, he added.
However, a genetics expert not connected to the study was more cautious about
drawing implications from its findings.
How the research was done
Bipolar disorder, also known as manic-depressive illness, affects about 5.7
million American adults, or about 2.6% of the US population aged 18 and older,
according to the US National Institute of Mental Health (NIMH). The brain
disorder causes severe and unusual shifts in mood, energy, activity levels, and
the ability to carry out routine daily tasks.
The new research, published in a recent issue of the journal Bipolar
Disorders, involved examining 26 brains donated to a non-profit brain bank.
Fourteen of the brains were from people who had bipolar disorder. Of those,
seven were from people who had been taking one or more anti-psychotic
medications - such as clozapine, risperidone and haloperidol - when they died.
Twelve brains were from those with no mental health condition.
In comparing the brains, the scientists observed that the genes of those that
had been exposed to anti-psychotics at the time of death or during their
lifetime were similar to those from people who did not have bipolar disorder.
This suggests that the drugs may normalise or suppress the kinds of brain
pathology one would expect in bipolar disorder, according to the
A step towards 'radical evolution'
The study also supports the idea that the ability of brain cells to
effectively communicate with each other may be impaired in people with bipolar
The researchers found that the brains of people who were taking
anti-psychotics and those who did not have bipolar disorder showed striking
similarities in how their brains relayed signals between cell gaps, or synapses,
and on high-speed neuronal "freeways" called the nodes of Ranvier.
While anti-psychotic medications can often be effective in moderating the
effects of bipolar disorder, the side effects are often difficult for people to
deal with. These include metabolic syndrome - a combination of symptoms that
increase the risk of developing cardiovascular disease and diabetes - as well as
weight gain, increased blood sugar levels, and tremors, McInnis said.
However, one expert expressed some concerns about the study.
"It's still not known if these changes just happen to occur or play a key
role in the therapeutic effect," said Dr Francis McMahon, chief of the human
genetics branch at the NIMH Intramural Research Program.
McMahon also noted that the researchers don't have data on what medications
the brains were exposed to during their lifetimes. "Patients [with bipolar
disorder] are exposed to antidepressants, drugs of abuse, and other medications,
and we don't have medication exposure data on the brains [of the people without
For his part, study author McInnis said the research represents a step toward
a radical evolution in the design of drugs for psychiatric conditions by the
"A lot of these psychiatric illnesses fluctuate, but now we give medications
at a constant rate, almost as if we were giving a diabetic the same amount of
insulin no matter what the person's blood sugar is," McInnis said. "Medications
as we know them will change based on our understanding of the biological
mechanisms behind disease."