Enlarged amygdala involved in psychiatric challenges in young girls with autism

Newswise — Preschool-age girls with autism spectrum disorder (ASD) face greater challenges with emotional and behavioral problems than similar age boys with ASD. These challenges are associated with a larger amygdala, a UC Davis Health study has found. The amygdala is a key part of the brain that helps regulate emotions and detects threats.

The findings, by Christine Wu Nordahl, associate professor in the UC Davis Department of Psychiatry and Behavioral Sciences, and colleagues at the UC Davis MIND Institute, suggest that amygdala development may help predict these psychological and behavioral problems that can occur at high rates in girls with ASD. The study was published online Jan. 19 in the Journal of the American Academy of Child & Adolescent Psychiatry.

“A significant number of individuals with autism have co-occurring psychiatric problems like ADHD, anxiety and depression,” said Nordahl, a scientist who specializes in neuroimaging. “There are treatments for these conditions that can reduce the challenges in their lives. But less is known about whether these problems are present in very young kids.

“I was interested in looking for early signs of these symptoms in 3-year-olds with autism and whether girls and boys are affected at the same rates. I also wanted to investigate the underlying brain basis for these symptoms. The amygdala is a likely target because of its role in emotion regulation. Amygdala enlargement has been reported both in autism as well as psychiatric problems like anxiety.”

Psychopathology symptoms in very young children can include frequent crying, poor eating habits, trouble sleeping, overeating, little interest in daily activities, inability to sleep alone, nervousness, frequent panic, inability to sit still or concentrate and being highly demanding.

Study focused on 3-year-olds diagnosed with autism

This study included 420 children (91 girls and 209 boys with ASD, and 57 girls and 63 boys developing typically who served as the control group). The scientists conducted MRI scans on 346 children as they slept to evaluate amygdala volume. Study participants also were evaluated on their psychopathology symptoms, as reported by a parent, as well as their adaptive functioning, cognitive development (IQ) and autism severity.

Researchers identified three subgroups of children with ASD:

• Over one quarter of the 3-year-olds with ASD (27%) had very high symptoms of psychopathology with moderate impairments on other measures such as IQ, daily living skills, and autism severity
• 40% had low levels of psychopathology and low levels of impairment on the other measures
• 32% had low levels of psychopathology but high levels of impairment on the other measures

Notably, a surprisingly high proportion of girls with autism (40%) were in the subgroup with very high levels of psychopathology. The remaining 60% of girls with ASD were more evenly split across the two other groups. In contrast, only about 20% of boys with autism were in the subgroup with high levels of psychopathology, and most boys (45%) were in the subgroups with the lowest levels of impairment on all measures. 

When examining associations between amygdala volume and the subgroups of children with ASD, they found amygdala enlargement only in the children who also had high levels of psychopathology. They also found that the size of the amygdala was correlated with the severity of the problems in girls, but not boys.

“We think the larger amygdala volume is playing a role in these other co-occurring problems,” Nordahl said. “And the amygdala is playing more of a role in these problem behaviors in girls than in boys.”

Study sheds light on biological differences in girls with autism

The research is significant because it begins to explain some of the biological differences in girls with ASD, who are diagnosed with autism much less frequently than boys at a ratio of about 1 girl for every 4 boys, Nordahl said.

“Girls are really underrepresented in autism research, particularly in neuroimaging studies,” she said. “Because there are so many more boys than girls diagnosed with autism, girls are harder to recruit, and most studies do not include enough girls to meaningfully evaluate potential sex differences. The result is that we know very little about how girls with autism may be similar or different from boys, particularly from a neurobiological perspective.”

The findings are among the first to come out of the Girls with Autism Imaging of Neurodevelopment (GAIN) study at the MIND Institute, which seeks to better understand their brain structure and connectivity patterns. With nearly 100 girls with autism enrolled, it is the largest neuroimaging study ever conducted in very young girls at the time of diagnosis.

“Over the past decade, our research team has spent countless nights at the UC Davis Imaging Research Center working with families to help children feel comfortable enough to fall asleep for an MRI scan. Across several projects, our team has collected over 1,000 MRI scans in more than 450 children.”

Researchers to continue to follow participants into adolescence

Researchers hope to follow the study participants into middle childhood and adolescence. Those are the years when psychiatric conditions such as anxiety and depression are typically diagnosed.

“We want to continue to see how the amygdala develops and determine whether it will have a predictive role in the outcomes for these kids,” said Nordahl.

Until then, she said, the current findings may be helpful for parents with young children diagnosed with autism.

“It’s important for parents to be on the lookout for problem behaviors co-occurring with autism, particularly in girls,” said Nordahl. “If we can detect symptoms of psychopathology earlier, we may be able to intervene earlier to help children and their families before psychiatric problems become too debilitating.”

Other authors on the study include Ana-Maria Iosif, Gregory S. Young, Alexa Hechtman, Brianna Heath, Joshua K. Lee, Breanna Winder-Patel, David G. Amaral, Sally Rogers, Marjorie Solomon and Sally Ozonoff, all of UC Davis Health, and Lauren Libero and Vanessa P. Reinhardt, former post-doctoral researchers at the MIND Institute.

The research was funded with grants from the National Institutes of Health (RO1MH104438, R01MH103284, R01MH103371) and UC Davis MIND Institute. The project also was supported by the MIND Institute Intellectual and Developmental Disabilities Research Center (U54HD079125), MIND Institute Autism Center of Excellence (P50 HD093079), the MIND Institute Autism Research Training Program (T32MH073124) and University of California President’s Postdoctoral Fellowship.