Complex immune and metabolic reasons for anxiety in kids

Anxiety runs high in so many kids these days and sometimes a child’s anxiety does not respond to the usual nutrition and gut work. And even when the food is nutritious, the supplements are in place and the gut is happier, they still feel anxious and on edge much of the time. That is when we at NatureDoc go looking for the deeper drivers of anxiety from infections to metabolic reasons.

This is the third blog in my series on nutrition for anxious children. The first covered the basics of nutrients and habits. The second explored the gut–brain link, dysbiosis and SIBO. This one is for the families who have done all of that (or suspect that the other reasons are not their child’s issue) and they still feel something is missing. If your child’s anxiety came on suddenly, has dramatic ups and downs, or runs alongside other unexplained symptoms, please read on.

PANS and PANDAS: when an infection sets off the brain

PANDAS stands for Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections. PANS (Paediatric Acute-onset Neuropsychiatric Syndrome) is the broader umbrella of these conditions, where infections other than strep, or other inflammatory triggers, can set off the same picture.

Very often, there is a sudden onset of anxiety from a child who is usually happy-go-lucky, and it does not go away, and sometimes it is sitting in the background or waxes and wanes. Often a PANS or PANDAS flare looks like a child who normally manages fine, suddenly develops severe OCD, tics, separation anxiety, eating restriction, dramatic mood swings, and regression in handwriting or school skills. It often follows a sore throat, scarlet fever, the flu, chickenpox, COVID, or other infection by a few days to a few weeks. Some parents describe their child as a “different character overnight” but this is not always the case.

The mechanism of PANS/PANDAS is autoimmune and inflammatory. It is where the immune system, while fighting the infection, produces antibodies that cross-react with the basal ganglia at the back of the brain and this drives autoimmune-mediated inflammation. The basal ganglia is the area of the brain that governs movement, mood regulation and the brakes on intrusive thoughts.

You may be lucky to find a GP who has come across PANS/PANDAS and there are now a few private specialists. Reducing the effects of a PANS/PANDAS flare usually combines treating the underlying infection (often with antibiotics for streptococcal infections), reducing inflammation and supporting the nervous system through nutrition. Nutritional support around immune modulation, such as vitamin D, omega-3s, zinc, magnesium, and gentle anti-inflammatory foods, is a sensible add-on alongside any medical care.

If your child’s anxiety appeared abruptly, especially if it also comes along with OCD, tics, urinary changes or food restriction in the mix, seek medical help as soon as you can as earlier recognition and treatments tend to mean better outcomes. Have a read of my blog and listen to my podcasts on PANDAS if you have just had a lightbulb moment about your child.

Low cholesterol: when the brain is running on empty

Most of us spend our adult lives worrying about our cholesterol becoming too high. But in children with anxiety, very low cholesterol can be a real problem. Around 25% of the body’s cholesterol is in the brain and it is the raw material for making cell membranes, myelin (the insulation around nerves), bile acids, vitamin D and steroid hormones including cortisol, oestrogen and testosterone. Without enough cholesterol, the brain cannot communicate properly, and the wheels start falling off in terms of mood and emotional regulation.

Studies have linked low total cholesterol with higher rates of depression, anxiety, impulsivity and suicidal behaviour in both adults and adolescents. In children with restrictive eating, poor fat absorption, coeliac disease or rare genetic conditions affecting cholesterol synthesis (such as Smith–Lemli–Opitz syndrome), the levels can drop low enough to affect behaviour, sleep and mood directly.

At NatureDoc we always look at total cholesterol in a child’s routine blood test. If it is under 4.2 mmol/L in a child with anxiety, we always want to understand why. Often the cause is straightforward such as a very low-fat diet and fussy eating (the kids that live off dry cereal and pasta), or undiagnosed coeliac disease affecting fat absorption. The fix is usually to add back nutrient-dense fats including eggs, liver, heart, oily fish, grass-fed butter, full-fat dairy, avocados, olive oil and nuts. Most children’s cholesterol and mood lift together within a few months once their body and brain are getting enough good quality fats.

Kryptopyrrole: a depletion of zinc and vitamin B6

A condition called pyroluria, also known as kryptopyrrole is particularly common amongst neurodivergent children. It is an inherited condition where essentially the urine excretes zinc and vitamin B6 faster than the diet can keep up. The theory is that some people produce excess hydroxyhaemepyrroline-2-one (HPL) in their urine, which binds tightly with zinc and vitamin B6, leaving the body chronically short of both. Because zinc and B6 are essential for serotonin, GABA and stress regulation, the result can be anxiety, mood swings, poor stress tolerance and emotional reactivity. The child is also often very particular about what they will and won’t eat and are drawn to solo activities such as gaming.

Kryptopyrrole can be tested through a simple and inexpensive urine test, and raising zinc and vitamin B6 levels through diet and supplementation can make a difference to the child’s ability to regulate within a couple of months.

The GABA-glutamate balance

GABA and glutamate are the brain’s yin and yang chemicals. Glutamate is the main excitatory neurotransmitter, and it gets neurons firing and the brain feeling revved up and sharp. GABA is the main inhibitory one and it calms the neurons down and makes a person feel safe and chilled out. A healthy brain keeps these in dynamic balance.

However, in anxious children, the balance often tips towards too much glutamate and not enough GABA, leaving the brain stuck in an over-excited state which can lead to excessive anxiety and rumination about the past. Parents describe their child as getting stuck in a loop of repetitive negative thoughts.

Several things push this balance the wrong way. Many people are born with a genetic profile which skews them more towards high glutamate and away from benefiting from the calmness of GABA. These genetic SNPs include GAD1, GAD2 and GABRA1.

Chronic stress also depletes GABA and important to consider. Depletions in key nutrients such as magnesium, B6 and zinc also reduce GABA production. The diet can count too and a high intake of free-glutamate from highly processed ingredients such as MSG, hydrolysed proteins, yeast extract, natural flavourings and citric acid adds to this excitatory load.

Practical ways to support the balance:

• Top up the GABA-making nutrients which include magnesium, B6, zinc and taurine
• Reduce free glutamate where possible and cut back on stock cubes, flavoured crisps, ready meals, broth concentrates and yeast extract spreads
• Add foods that support GABA foods such as oats, barley, brown rice, spinach, kale, sweet potato, broccoli, cauliflower, beans, chestnuts, live yoghurt and kefir.
• Use calming herbal support including lemon balm, theanine, chamomile and passionflower

Other deeper drivers worth knowing about

HPA-axis dysregulation

When a child has been under chronic stress for a long time due to a high-pressure school, trauma or ill health, the HPA axis (the system that produces cortisol) can become dysregulated. This can mean it is sometimes running too high and sometimes running too low. Saliva cortisol testing through the day can be revealing if there is a mixed picture and this can be arranged through our clinical team for teenagers and young people.

Support for HPA-axis dysregulation is usually a combination of nervous system work such as prioritising good quality sleep and downtime as well as vagus nerve practices. You can also consider adaptogenic herbs such as ashwagandha, rhodiola or holy basil as well as rebuilding any nutrient reserves.

Histamine and mast cell activity

Some anxious children also struggle with having high histamine levels. To spot if this is their issue, look out for symptoms such as flushing easily, itchy skin or orifices, having hay fever, asthma or eczema, reacting to fermented foods or aged cheese, and they may also have unexplained tummy symptoms.

Histamine used to be classed as a neurotransmitter, and it speeds up the brain: this is why high histamine in the brain can feel exactly like anxiety. Very often the high histamine child is bright academically but feels on edge and finds it hard to relax. Calming the histamine load can be through avoiding high histamine foods and fermented foods and by adding in quercetin, vitamin C or PEA and these measures can be transformative for these children.

Thyroid function

Both an over-active and under-active thyroid can look like anxiety in children. If your child has weight changes, temperature dysregulation, tremor, hair loss or fatigue alongside their anxiety, then ask for a full thyroid panel (TSH, free T4, free T3 and thyroid antibodies, not just TSH on its own) to check to see how their thyroid is fairing. A thyroid needs to be fed with foods containing selenium like Brazil nuts, as well as zinc from seeds and shellfish and iron from red meat and greens.

Round up

If your child’s anxiety has not responded to the nutrient and gut work in the first two blogs of this series, do not assume nothing more can be done, and this is the time to look harder. Was there a sudden onset, or an obvious infection in their health history? Have they got OCD or tics in the mix? Has their handwriting changed? Are they eating very low-fat? Do they fit a classic histamine or thyroid picture? These are all clues that one of the deeper drivers may be at play.

If this blog has rung bells for you, then get in touch with our NatureDoc clinical team. We will look at your child’s whole picture, order the right tests, and build a plan that is tailored to them. Many of the families we see have been through years of feeling unheard, and finally understanding the biology behind their child’s anxiety is a turning point.

And if this series has been useful, please share it with another family who might find it helpful. So many parents are looking for the missing piece for their anxious child and sometimes knowing where to look is the first step to getting them back.

This blog was originally published on 27th February 2017 and has been updated to reflect new research.

References

• Pediatric acute-onset neuropsychiatric syndrome and PANDAS: a Delphi study and consensus document on definition, diagnosis, treatment and follow-up
• Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part II — use of immunomodulatory therapies
• Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part III — treatment and prevention of infections
• Treatment of PANDAS and PANS: a systematic review
• Treatment barriers in PANS/PANDAS: observations from eleven health care provider families
• Sixty years of conjecture over a urinary biomarker: a step closer to understanding the proposed link between anxiety and urinary pyrroles
• Serum cholesterol concentration, depression, and anxiety
• Cholesterol and suicide attempts: a prospective study of patients hospitalised for depression
• Smith-Lemli-Opitz syndrome: Clinical, biochemical, and genetic insights with emerging treatment opportunities
• Effects of green tea amino acid L-theanine on stress and anxiety: a systematic review
• Glutamate Systems in DSM-5 Anxiety Disorders: Their Role and a Review of Glutamate and GABA Psychopharmacology
• The Loss of Glutamate-GABA Harmony in Anxiety Disorders
• Could Free Glutamic Acid in Processed Food be the Surprise Ingredient in Mood Disorders?
• Could dietary glutamate play a role in psychiatric distress?
• Anxiety and methylenetetrahydrofolate reductase mutation treated with S-adenosyl methionine and methylated B vitamins
• Inflammation in anxiety
• Histamine intolerance: the current state of the art
• The Association between Depression, Anxiety, and Thyroid Disease: A UK Biobank Prospective Cohort Study
• Hypothyroidism and hyperthyroidism in anxiety disorders revisited: new data and literature reviewv
• The effect of adaptogenic plants on stress: A systematic review and meta-analysis
• The role of zinc in the treatment of anxiety and mood disorders
• Pyrroles as a Potential Biomarker for Oxidative Stress Disorders
• Cross-Sectional Analysis of Pyrroles in Psychiatric Disorders: Association With Nutritional and Immunological Markers
• Sixty years of conjecture over a urinary biomarker: a step closer to understanding the proposed link between anxiety and urinary pyrroles