Why does PANS/PANDAS so often appear around seven?
Seven is an interesting age in PANS and PANDAS.
We certainly see children who develop symptoms much younger, and others much later, but in our clinic there has always seemed to be a cluster around seven or eight. I had assumed this was simply one of those patterns you start to notice after seeing enough children.
Then I looked at the published data.
Across several PANS cohorts, the average age of onset is around seven to eight years. In one Stanford cohort it was 7.5 years. Even in the original PANDAS work, the average age of onset was 6.3 years for children presenting with tics and 7.4 years for those presenting with OCD.
That made me curious about what else is changing around this age.
One possible answer is adrenarche.
What is adrenarche?
Adrenarche is one of the first hormonal shifts of childhood and it happens well before the puberty most parents are watching for. There may be no breast development, periods or breaking voice. But from around six to eight, the adrenal glands are already beginning to produce increasing amounts of hormones including DHEA and DHEAS.
In other words, a child can look nowhere near puberty while their hormonal environment has already started to change.
Hormones and the immune system
I became more interested in this after reading a review on sex hormones and the immune system. It has nothing to do with PANS or PANDAS specifically, but it describes something that feels very relevant here.
Hormones and the immune system are much more closely connected than we realise. Immune cells have receptors for sex hormones, which means hormones can influence the way the immune system behaves.
This can affect T cells, B cells, antibody production and inflammatory signalling. But the part that caught my attention was immune tolerance.
Our bodies naturally produce some immune cells that are capable of reacting against our own tissues. Usually they are removed, switched off or kept under control. In animal studies, oestrogen has been shown to influence some of these checks, allowing certain self-reactive B cells to survive and produce antibodies.
And this is where I started thinking about adrenarche.
As DHEA and DHEAS begin to go up, the hormonal environment is changing. These adrenal hormones can also be converted into androgens and oestrogens, so there are several ways this shift could interact with the immune system.
None of this tells us that adrenarche is driving PANS or PANDAS. We don't have evidence for that. But if immune tolerance and antibody responses are already part of the picture, I think this hormonal shift is worth looking into.
What the trigger doesn't explain
We spend a lot of time looking at what happened just before a child changed. In PANDAS, strep is the obvious one. With PANS, the list of possible triggers is much wider. Parents can often take you back to the exact illness, and sometimes the exact week, when they first noticed something was wrong.
What is harder to understand is why the same thing can look so different another time.
These children have been ill before. They have had strep, viruses, stomach bugs and fevers, often many times. Most of the time they recover and life carries on as normal.
And sometimes it doesn't.
An infection that might once have meant a sore throat and a few miserable days is followed by OCD, tics, food restriction, separation anxiety, urinary frequency, rage, regression or a child who suddenly seems very different to their parents.
The infection matters, of course. But I am increasingly interested in what else might have been changing in the child at the same time.
What we don't know yet
I don't think we know yet whether adrenarche has anything to do with this. There is no study showing that the hormonal changes of adrenarche cause PANS or PANDAS, and children can develop PANS at ages where this explanation simply wouldn't fit.
There are other reasons why seven might keep appearing in the data. Strep throat is particularly common in school-age children, and the original PANDAS criteria required symptoms to begin before puberty. Either of those could pull the average towards the younger years without hormones being involved at all.
Even so, I keep coming back to the same question: does adrenarche change anything in a child who is already susceptible?
It may turn out that it doesn't. But if it does, it could change the way we think about this age altogether. Instead of only reacting after a child becomes unwell, perhaps one day we could recognise a period of greater vulnerability and support these children before the next infection comes along.
Asking a second question
So rather than only asking, “What triggered this?”, I think there is another question worth asking:
Maybe the trigger is only half the story. Maybe timing is the other half.
IMPORTANT
This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis or treatment. Always consult with medical doctors or qualified functional medicine practitioners before introducing any new supplement, test, or intervention.
If this has raised questions about your child, we'd love to help you find some answers.
REFERENCES
Ma M, Masterson EE, Gao J, et al. (2024) Development of autoimmune diseases among children with pediatric acute-onset neuropsychiatric syndrome. JAMA Network Open 7(7):e2421688.
Masterson EE, Gavin JM (2024) Baseline characteristics of children in the International PANS Registry (IPR) Epidemiology Study. BMJ Open 14(1):e072743.
Moulton VR (2018) Sex hormones in acquired immunity and autoimmune disease. Frontiers in Immunology 9:2279.
Rosenfield RL (2021) Normal and premature adrenarche. Endocrine Reviews 42(6):783-814.
Swedo SE, Leonard HL, Garvey M, et al. (1998) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. American Journal of Psychiatry 155(2):264-271.
Witchel SF, Pinto B, Burghard AC, Oberfield SE (2020) Update on adrenarche. Current Opinion in Pediatrics 32(4):574-581.
