Using hundreds of brain scans, neuroscientist Janna Marie Bas-Hoogendam and American child and adolescent psychiatrist Daniel Pine investigated whether the risk of developing social anxiety can be detected at an early age by examining the anatomy of the brain. Their article has now been named Paper of the Year by the American Academy of Child and Adolescent Psychiatry.
Freezing when a stranger enters the room, retreating to a parent's lap or being reluctant to approach other children: inhibited behaviour in childhood is strongly associated with social anxiety disorder later in life. But is this inhibition also reflected in the brain, and could brain scans therefore help identify the early signs of social anxiety disorder?
Paper of the year
This was the question Janna Marie Bas-Hoogendam set out to answer with the Rubicon grant she received from the Dutch Research Council (NWO) in 2020. The Rubicon grant is officially intended to support researchers in setting up a research project abroad, 'but because of Covid, I worked from home with Daniel and his team at the National Institute of Mental Health in Bethesda, USA.' In 2025, the paper she co-authored with Pine, his team and members of the international ENIGMA-Anxiety working group was published: Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-Analysis. On 30 October, they presented their findings at the annual meeting of the American Academy of Child and Adolescent Psychiatry in Atlanta, where their article was named Paper of the Year and received the Norbert and Charlotte Rieger Award for Scientific Achievement.
Hundreds of brain scans
'We collected hundreds of brain scans from research centres around the world,' Bas-Hoogendam explains. 'That's also why the paper has dozens of authors: all the researchers who contributed their data to the analysis.' The researchers carefully prepared the introduction and methodology and submitted them to colleagues at the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) for peer review before beginning their analyses, as a registered report. 'Only once the methodology had been approved and published in the journal did we carry out the analyses. We followed the preregistered methodology precisely, which meant that we could subsequently publish the full article in JAACAP, regardless of the results.'
No strong link between brain scans and social anxiety
'We looked for associations between the degree of behavioural inhibition in children and their brain structure. We wanted to know whether early signs of anxiety that children might develop later in life could already be detected in the structure of their brains.' The analyses suggested that this was not really the case. 'Most of our findings were null results, which are normally quite difficult to publish. But in this case, we could publish them because the methodology had been approved in advance.'
Different ways of measuring inhibition
The studies included in Bas-Hoogendam and Pine's paper used different methods to measure behavioural inhibition. 'We brought together as many datasets as possible, but they differed considerably in how researchers had assessed inhibited temperament. In some studies, young children were exposed to unfamiliar situations in a laboratory, such as a stranger entering the room or a moving robot, and researchers recorded their reactions. In others, parents and teachers described their perceptions of the child's behaviour, while in yet other studies, young people reported retrospectively on how they had behaved as children.'
No significant association
Across all these different methods of measuring behavioural inhibition, the researchers found no significant association between brain structure and inhibited temperament. 'We also conducted separate analyses for each of the three subgroups, but again found no consistent, statistically significant associations.'
No news is news too
Studies that do not produce striking results often remain unpublished. 'But publishing these kinds of null findings is extremely important to ensure that the scientific literature accurately reflects the research that has been conducted,' Bas-Hoogendam explains. 'This helps prevent certain associations and effects from appearing stronger than they actually are, while results that fail to confirm those associations remain hidden away in a drawer. This is known as the "file-drawer effect".'
Large datasets
One of the features that makes this research unique is the researchers' ability to combine data from so many different studies. 'Previous studies were often small-scale, involving relatively small groups of children and adolescents. That's understandable, because this type of research, which examines behaviour and neurobiology together, is labour-intensive and expensive. The downside, however, is that the findings of these earlier studies, each with a slightly different focus and methodological approach, often contradicted one another,' Bas-Hoogendam explains.
A solid starting point
By conducting a mega-analysis within the ENIGMA-consortium, researchers can assess whether consistent and reproducible patterns can be identified. 'This type of analysis produces more reliable results, which is extremely important for developing effective interventions, for example. You need a solid starting point for that, and large datasets are essential for establishing such a foundation.'
