Evaluation of Generalized Joint Hypermobility and Serum Prolidase Levels in Children Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Compared to Healthy Controls
This study demonstrates that children with ADHD exhibit significantly higher serum prolidase levels and a greater prevalence of generalized joint hypermobility compared to healthy controls, suggesting that altered connective tissue turnover may be a distinct biochemical feature in a subgroup of these patients.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
For decades, doctors have noticed that children with attention-deficit/hyperactivity disorder, or ADHD, often struggle with more than just focus and impulse control. Many of them also have bodies that seem to move differently, with joints that bend further than usual and a higher tendency to feel pain in their muscles and bones. This connection has long been observed, but the reason behind it remained a mystery. Scientists knew that both conditions involve collagen, a tough, fibrous protein that acts as the body's internal scaffolding, holding tissues together and giving them structure. They also knew that the body constantly breaks down and rebuilds this collagen, a process managed by specific enzymes. The question was whether the way a child's body handles this collagen turnover might be the hidden link between a busy mind and a flexible body.
A team of researchers in Turkey set out to investigate this possibility by looking at a specific enzyme called prolidase. This enzyme is the gatekeeper for breaking down collagen; without it, the body cannot recycle the building blocks of its connective tissues efficiently. While this enzyme had been studied in adults with joint problems, no one had ever measured it in children with ADHD. The researchers wanted to see if the levels of this enzyme in the blood could explain why so many children with ADHD also have loose, hypermobile joints. They recruited 171 children between the ages of six and twelve, splitting them into two groups: 86 children who had been clinically diagnosed with ADHD and 85 children who were developing typically without any known psychiatric conditions.
To get a clear picture, the team used a careful, step-by-step approach. A specialist in physical medicine, who did not know which children had ADHD and which did not, examined every child's joints. They used a standard nine-point test to measure how far the joints could move, looking for signs of generalized joint hypermobility. At the same time, the children's parents filled out detailed questionnaires about their child's behavior, and the children themselves reported how much pain they were feeling. Finally, the researchers drew a small amount of blood from each child to measure the exact amount of prolidase circulating in their system.
The results revealed a striking difference between the two groups. Children with ADHD were far more likely to have hypermobile joints; nearly 67 percent of them met the criteria for joint laxity, compared to only about 26 percent of the children in the control group. More surprisingly, the children with ADHD also had significantly higher levels of prolidase in their blood. The median level in the ADHD group was 326.3 nanograms per milliliter, while the control group averaged 249.9 nanograms per milliliter. This difference was substantial and remained true even after the researchers accounted for other factors like age, sex, body weight, and even low-level inflammation in the body.
The study also clarified what these numbers actually meant for the children's daily lives. The researchers found that the amount of prolidase in a child's blood was linked to how loose their joints were, but it had no connection to how severe their ADHD symptoms were. In other words, a child with very high enzyme levels did not necessarily have more trouble paying attention or controlling impulses than a child with lower levels. Similarly, the children who reported feeling more pain were the ones with the most flexible joints, not necessarily the ones with the ADHD diagnosis. This suggests that the pain these children feel is likely a physical result of their loose joints rather than a side effect of their behavioral condition.
One of the most important findings was that the diagnosis of ADHD and the presence of loose joints acted as two separate factors that added up, rather than one causing the other. The high levels of prolidase appeared to be a characteristic of the connective tissue itself in these children, existing independently of their behavioral symptoms. While the researchers noted that their findings contrast with some earlier studies on adults, where enzyme activity was found to be lower, they explained that they measured the actual amount of the enzyme protein, not just how fast it was working. This distinction is crucial, as it points to a different kind of biological process at play in children.
The study concludes that a specific subgroup of children with ADHD may have a unique type of connective tissue that turns over differently than in other children. This biological difference helps explain why so many of them have flexible joints and why they might experience physical pain. However, the researchers are careful to state that measuring prolidase in the blood should not be used as a diagnostic test for ADHD. Instead, these findings offer a new way to understand the physical side of the condition, suggesting that doctors should look at the whole child, including their joints and pain levels, rather than focusing solely on behavior. The work highlights that for some children, the mind and the body are connected through the very structure of their tissues, offering a clearer path for future research and better care.
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