Brain Anatomy Differences In 22q11.2 Genetic Neuropsychiatric Risks

Brain differences between people with a specific genetic risk for schizophrenia and those at risk for autism have been mapped in a new study from UCLA. These first time findings could help explain the biological underpinnings of these neuropsychiatric disorders.

The research offers insight into how an excess, or absence, of genetic material on a particular chromosome affects neural development.

“Notably, the opposing anatomical patterns we observed were most prominent in brain regions important for social functioning. These findings provide clues into differences in brain development that may predispose to schizophrenia or autism,”

said Carrie Bearden, lead author of the study and a professor of clinical psychology at UCLA.

22q11.2 Deletion Syndrome

Bearden’s earlier research had focused on children with abnormalities caused by missing sections of genetic material on chromosome 22, in a location known as 22q11.2.

The disorder, called 22q11.2-deletion syndrome, can cause developmental delays, heart defects and distinct facial features. It also confers the highest-known genetic risk for schizophrenia.

Then she learned that people with 22q duplication — abnormal repetition, or duplication, of genetic material in chromosome 22 — had learning delays and sometimes autism, but a lower risk for schizophrenia than that found in the general population. In other words, duplication of genetic material in this region seemed to provide some protection against schizophrenia.

For the current study, Bearden, who is part of the UCLA Semel Institute for Neuroscience and Human Behavior, conducted MRI scans of 143 study participants: 66 with 22q deletions, 21 with 22q duplications, and 56 without the genetic mutation.

Psychiatric Outcomes

Those in the group with 22q deletion, which carries the risk for schizophrenia, had thicker gray matter, but less brain surface area — a measure which relates to how folded the brain is — compared to those in the duplication group. The people in the 22q duplication group, who at risk for autism, had the opposite pattern, with thinner gray matter and larger brain surface area.

“The next question is how does brain anatomy, and brain function, relate to psychiatric outcomes? These findings provide a snapshot,” Bearden said. “We are now conducting follow-up studies to track predictors of outcome over time. Those are the puzzle pieces that are next on our list to disentangle.”

These structures are not sole determinants of schizophrenia or autism, Bearden said, but rather, more dots in the connect-the-dots puzzle of understanding these disorders. Observing this group of people over time could provide insights on how other risk factors or life events, such as puberty, affect the mind.

Bearden says she and her team are collaborating with other scientists to investigate brain structural differences in animal models, to find out what causes them at the cellular level.

Amy Lin, Christopher R. K. Ching, Ariana Vajdi, Daqiang Sun, Rachel K. Jonas, Maria Jalbrzikowski, Leila Kushan-Wells, Laura Pacheco Hansen, Emma Krikorian, Boris Gutman, Deepika Dokoru, Gerhard Helleman, Paul M. Thompson and Carrie E. Bearden
Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry
Journal of Neuroscience 23 May 2017, 3759-16; DOI:

Image: Nevit Dilmen CC BY-SA 3.0