Bipolar risk gene behavior revealed

Psychiatric risk gene, in detail

Cassidy Johnson

Psychiatric risk gene, in detail

By Contributing Writer Abby Seitz

New research from Northwestern University may provide a better understanding of the biological basis of neuropsychiatric diseases.

In a study published Oct. 22 in the journal Cell, NU researchers used super-resolution imaging to study cells from mice with behaviors similar to those of bipolar disorder. This is the first time a psychiatric risk gene has been analyzed at such a detailed level of resolution. 

The imaging revealed unanticipated structural and functional features of the synapses—the connections between nerve cells that neurotransmitters move across—called nanodomains.

Neuropsychiatric disorders such as bipolar disorder, schizophrenia and major depression affect approximately 61.5 million Americans every year, and one in 17 Americans lives with a serious mental illness on a consistent basis, according to the National Alliance on Mental Illness.

“We were using structured elimination microscopy, which works by basically shining patterned light over samples from different directions,” said Kate Smith, first author of the study and post-doctoral fellow at Northwestern University. “We can increase the resolution by reconstructing the images that we take. It means we can look at multiple proteins at the same time with high resolution.”

This neuropsychiatric risk gene, ANK3, was present inside of the nanodomain structures within the synapses of the mice. 

“Mutations and genetic risk conveyed by [this protein] can contribute in different ways to synapse structure function,” Smith said. “This protein is found in synapses in the brain. We think the problem with the protein is caused by genetic mutations or disruption of its function, which will then cause problems in the communication between brain cells.”

According to Peter Penzes, co-author of the study and associate professor of physiology, psychiatry and behavioral sciences at Northwestern University’s Feinberg School of Medicine, it is not yet clear what change is taking place in the gene that is resulting in the symptoms of bipolar disorder and other neuropsychiatric ailments.

“A difference in sequencing in the gene between normal people compared with patients [who suffer from mental illness] could represent a mutation that results in a faulty protein,” Penzes said. 

Recent genetic studies looking at schizophrenia, bipolar disorder and autism have concluded that there is no single gene that causes neuropsychiatric disease. In more severe cases, variation in genetic sequencing can result in intellectual disability or mental handicap, Penzes said. Post-mortem studies have found fewer synapses in the brains of people who suffered from neuropsychiatric disorders, but there was no clear connection between the two.

“This gene is affecting the risk of [occurrence] of bipolar disorder that causes the same changes in synapses detected in brain tissue of patients,” Penzes said.

Brittany Ruby, a clinical intern  in the college’s Office of Counseling Services, said bipolar disorder is characterized by episodes of depression, anxiety and mania. 

“When someone is manic, it’s kind of the opposite of depression,” Ruby said. “They might find they have a lot more energy than they normally do or feel like they don’t need as much sleep.”

According to Ruby, these symptoms can also result in risky behaviors that the person may not have otherwise taken part in. People experiencing the symptoms do not necessarily view them as negative although they can have destructive consequences, which is common because mania is punctuated by moments of alternating high and low moods.

“There are some medications available [for treatment], like mood stabilizers or antidepressants, but their prescription depends on the type of symptoms presented, the severity of those symptoms and the mental state of the patient,” Ruby said. “The process of [medicating patients] can be really hit or miss. Typically, research has found a combination of medication and psychotherapy to be the best approach.”

Penzes said a big challenge in psychiatry is to try to understand the processes that occur in the brain that result in disease because psychological evaluations and behavioral analysis often do not reveal a definitive, treatable cause. Recent studies have also found that the synaptic connections between brain cells are affected in the presence of symptoms of disease.

“It’s not like a diagnosis of diabetes, where you can measure something to determine the difference between a healthy person and someone with the disease. It’s a big challenge to understand what’s happening specifically in the brain,” Penzes  said.  “If we can understand the specific molecules that regulate these [connections in the brain], we can attempt to design drugs to alter them and correct the changes in the brains of patients.”