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German researcher investigates structural brain changes in autism, schizophrenia

A German researcher and clinician, who recently joined the Psychiatry faculty and Iowa Neuroscience Institute (INI), is combining genetics and neuroimaging to investigate how brain structure is altered in autism and schizophrenia.

“It is absolutely intriguing to me that psychiatric disorders have a fingerprint in the brain,” said Thomas Nickl-Jockschat, MD, associate professor of psychiatry.  

Nickl-Jockschat initially focused on brain changes in patients with schizophrenia, but he widened his scope to include autism after attending an international graduate school program facilitated between RWTH Aachen University, where he received his resident training in Germany, and the University of Pennsylvania.  

He also met Ted Abel, PhD, now the director of the INI, during the program and was introduced to the idea of incorporating animal models in his research. The two went on to write a textbook together, titled “The Neurobiology of Schizophrenia” and currently collaborate on research projects within the INI.  

“As I began to work on these two disorders, we came to a frustrating point,” he said. “Most risk gene variants for autism and schizophrenia have really low odds ratios, which means you need large cohorts to detect the effects that these changes cause in brain structure. Some larger genomic variants have much larger effect sizes, but are extremely rare in the general population. I talked to Ted [Abel] and I was immediately intrigued by the idea of using mouse models of these rare variants.”

Although his move to Iowa has shifted his focus to looking at molecular pathways that underlie brain structural changes in mice, he also hopes to keep pursuing research with human subjects and seeing patients on the department’s psychiatric units.

“If you don’t see the patients then you forget what you’re actually working for,” he said. “We’re working for these people.”

Uncovering the connection between brain structure and disease

Understanding the biological basis of schizophrenia symptoms is another focus of the lab. There are both negative and positive symptoms that patients with schizophrenia. Hallucinations and delusions are positive symptoms and can often be managed with current medications. The negative symptoms, such as losing the ability to think abstractly, are harder to treat because it’s still unclear where they emerge from, he said.

He’s seen changes in the fronto-temporal regions in patients with schizophrenia, which are vital areas in language along with emotional processing.

“What we know from the literature is that these brain structural changes obviously have some kind of relationship to negative symptoms,” he said.

The next step for Nickl-Jockschat is working to understand the molecular underpinnings of these changes and how they relate to specific symptoms, which will ultimately lead to better treatments.

In autism, the biggest structural changes are seen in the occipital lobe, specifically the secondary visual cortex, he said. This region is involved in motion processing and is part of a larger network that is engaged in facial processing.

This region of the brain tends to be dysfunctional in patients with autism and is one of the factors that may lead them to make infrequent eye contact and have difficulty interpreting facial cues.

Nickl-Jockschat made the move to Iowa in order join the newly-established INI where he will have access to new resources and collaborations, but he heard about the University of Iowa years before he made the trans-Atlantic move.

“If you look at biological psychiatry, Iowa is a big name,” he said. “When I went to lectures as a student, Nancy Andreasen was the single living psychiatrist that was pointed out to me.”

Andreasen, MD, PhD, professor of psychiatry, is an internationally recognized neuroscientist and a leader in the field of schizophrenia research who pioneered the use of neuroimaging techniques to study brain abnormalities.  

“I found her data about the dynamic brain structural changes in schizophrenia and that inspired me and drove the interest in my work,” he said. “That was the reason I took up this research. Being here, where the spirit is alive, is absolutely fascinating.”

Wednesday, June 20, 2018