John Pietryka

Natural Health Expert & Medical Scientist

Adv. Dip. Health Sc. (Naturopathy), B. App. Sc. (Medical Laboratory Science), Adv. Dip. (Applied Biology) Member

ADD and ADHD Studies: A Comprehensive Review of the Literature

By John Pietryka

Posted  June 30 2017 | 0 Shares

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It’s normal to feel helpless or overwhelmed when you are the parent or guardian of a child with ADD or ADHD. Besides having a good relationship and communication with your doctors, however, one of the best things you can do is to arm yourself with knowledge. Luckily, there are a lot of ADD and ADHD studies available to the public.

What is ADHD?

Attention Deficit Hyperactivity Disorder (ADHD), previously known as hyperkinesis, is the most common behavioural disorder in children. It is estimated to affect 3 to 5 percent of school-age children. Frequently, the symptoms of ADHD appear together with learning problems, oppositional conduct disorder, anxiety, and depression.

Relatives of children with ADHD also have a higher incidence of neuropsychiatric disorders than relatives of families with no ADHD children. Conduct disorder, oppositional defiant disorder, major affective disorder (depression or bipolar disorder), anxiety disorder, including obsessive-compulsive disorder, and Tourette syndrome are seen more often in relatives of children with ADHD. Teenagers with ADHD, particularly untreated ADHD, are at risk for drug and alcohol abuse.

There are more boys than girls diagnosed with ADHD. Girls usually do not manifest disruptive behaviours to the extent seen in boys; girls with ADHD have half of the rates of conduct disorder and oppositional defiant disorder but are much more likely to have significant social problems. Compared with boys with ADHD, they manifest more emotional distress, have higher rates of depression and anxiety, are highly vulnerable to stress, and have poor self-esteem and a limited sense of control.

Here are ADHD studies regarding this topic:

Childhood ADHD and risk for substance dependence in adulthood: a longitudinal, population-based study.

The potential for misuse and abuse of medications in ADHD: a review.

When is ADHD not ADHD?

Some parents and teachers prefer children to be diagnosed with ADHD, if it means a pill can improve their behaviour. Claims of misdiagnosis are not uncommon. There are claims that a brief consultation with a doctor is insufficient time to be able to accurately diagnose ADHD in a child. A proper diagnosis requires a lengthy assessment with a behavioural specialist. Some children exhibit ADHD like symptoms and are mistakenly diagnosed as having ADHD.

Some other conditions that should be considered as affecting children’s behaviour are listed below:

  • Some children may have learning difficulties or dyslexia and dyscalculia (a specific learning disability in mathematics) and are often mistakenly diagnosed as inattentive ADHD
  • Auditory processing disorder
  • Oppositional defiance disorder
  • Epilepsy (an electroencephalogram is required to detect any epileptiform abnormalities), specifically absence seizures
  • A family history of Restless Legs Syndrome (RLS) is common in these children. Periodic limb movements in sleep may directly lead to symptoms of ADHD due to sleep disruption. Thus, when a child presents with symptoms of hyperactivity, inattention, irritability, and growing pains, the differential diagnosis and workup should include RLS in addition to ADHD. (Case 2: A 6-Year-Old Boy Who “Can’t Sit Still” Medscape Neurology & Neurosurgery. 2005; 7 (1): ©2005 Medscape)
  • Sleep disordered breathing
  • Exposure to caffeinated cola drinks impairs children’s learning ability by causing restlessness, hyperactivity, and inattention. Caffeine intake should be assessed as part of the evaluation. (Caffeinated Colas Linked to Inattention, Hyperactivity in First-Grade Children 2005 APA Annual Meeting: Abstract NR45. Presented May 23, 2005.)
  • In children with tics and obsessive/compulsive behaviours, including oppositional defiant behaviours, the possibility of Paediatric Autoimmune Neurodevelopmental Disorder Associated with Streptococcus infections (PANDAS) should be considered. This is a medical condition in which autoimmune antibodies to group A beta haemolytic streptococcus can in some children affect brain function, causing obsessive-compulsive disorder or symptoms of cognitive inflexibility, tics and ADHD.

SIGNIFICANCE OF PREGNANCY OUTCOMES

Intrauterine growth retardation is a risk factor for ADD/ADHD. Smoking is a major cause of growth retardation.

Very low birth weight may have severe cognitive impairment (25%), increased ADHD, and up to 60% need assistance at school and require special education. Birth trauma has been associated with increased incidence of ADHD.

OTITIS MEDIA – Chronic Ear Infections

  • Greater incidence of ADHD
  • Increased distractibility later in life
  • Lower IQ scores, poor performance on tests of reading, spelling, math, increased attention deficits, and increased behaviour problems at school
  • http://www.ncbi.nlm.nih.gov/pubmed/19037954
  • http://www.ncbi.nlm.nih.gov/pubmed/2304807

HEAVY METAL TOXICITY

Heavy metals, like mercury, copper, lead and aluminium, also inhibit neurotransmitter pathways and can interfere with the binding of the neurotransmitters with their receptors. Read more about heavy metal testing utilising a hair sample here.

FOOD SENSITIVITIES

Food sensitivities, artificial colours and flavours, and excessive phosphate ingestion seem to be an important causative factor in this disorder. Food sensitivities and food allergy provoke hyperactivity through partially digested food proteins (exorphins) entering the blood stream and scrambling the neuronal communicative system. In eight out of nine studies 86% of hyperactive children had elevated blood eosinophils, indicative of allergy or parasitic infection.

Artificial colours, flavours and preservatives inhibit a number of detoxifying enzymes (e.g. aryl sulphatase, catechol-o-methyl transferase), which increases the toxic effects of certain foods. Studies have linked ingestion of artificial food colourings and behavioural change in children. Irritability, restlessness and sleep disturbance have been specifically linked to food colourings such as tartrazine.

The most common chemicals children react to are amines, salicylates, artificial colours, glutamates and preservatives. Statistically significant improvements in conduct, learning, impulsivity and hyperactivity have been demonstrated if these are removed or minimised in the diet. Data from two double blind studies indicate that 73-76% of ADHD children respond favourably to food elimination diets. Maintenance on low-antigen diets raised the success rate to 82%.  

Calcium propionate (preservative code 282) is a colourless, tasteless and odourless preservative used in breads to discourage mould growth. Researchers in Darwin investigated the effects of 282 on behaviour on children with “behavioural problems”. The authors concluded that; the preservative may cause restlessness, inattention, irritability and sleep disturbance in some children.

ALTERED BRAIN GLUCOSE METABOLISM

Correct glucose metabolism in the brain is important for efficient cognitive function. Studies showing differences in brain glucose metabolism between ADHD patients and normal subjects, ADHD patients show 8.1% lower levels of brain glucose metabolism. Studies of diabetic children show significantly reduced attention, both at mild hypoglycaemia and also low normal blood glucose levels.

NEUROTRANSMITTERS

ADHD can be considered a disorder of neurotransmitter function, with particular focus on the neurotransmitters dopamine and serotonin.

DOPAMINE

Dopamine is the neurotransmitter that regulates the system that plays an important function in learning, motivation, goals, drives, and emotion, all of which are crucial to survival. There has been extensive research conducted that demonstrates that dopamine is critical in the regulation of learning, as well as maintaining trained or conditioned responses and motivated (goal-directed) behaviours. Dopamine also plays an important role in working memory, the ability to “keep something in mind” for a brief period of time.

A reduction of dopamine activity can cause diarrhoea, irritable bowel syndrome, cramps, nervous stomach, increased saliva, and raised insulin levels, and airways and cerebral blood vessels constrict. There may be faulty neurotransmission of dopamine, due to genetic variations of the dopamine receptor or a problem with dopamine re-uptake at the nerve junctions. This causes poor dopamine communication between neurons.

(The Nervous System. Henry Osiecki)

SEROTONIN

Serotonin is a neurotransmitter that has a calming effect on the brain. Low serotonin levels have been identified in ADHD, particularly in boys with aggressive symptoms. Increasing serotonin levels through appropriate supplementation has been shown to reduce aggressive symptoms.

In 1999, researchers at the Howard Hughes Medical Institute discovered that Ritalin and other stimulants exert their paradoxical calming effects by boosting serotonin levels in the brain. Elevating serotonin appears to restore the delicate balance between dopamine and serotonin and calms hyperactivity. Previously it was thought that the calming action of Ritalin worked through the neurotransmitter dopamine. From these results it was suspected that dopamine wasn’t the only key to understanding ADHD.  Their studies suggested that rather than acting directly on dopamine, the stimulants create a calming effect by increasing serotonin levels. The study concluded that the proper balance between dopamine and serotonin was the key, and that hyperactivity may develop when the relationship between dopamine and serotonin is out of balance.

PYROLURIA

Pyrolurias a genetic weakness where there is decreased activity of one of the enzymes involved in haemoglobin synthesis. This can result in abnormal haemoglobin synthesis and cause excess production of a by-product called kryptopyrrole. It has been suggested that pyroluria is heavily connected to certain mood disorders. Patients with high kryptopyrroles in their urine may present with severe mood swings, poor memory and explosive temper, may show signs of vitamin B6, B3 and zinc deficiency.

Some researchers report that high levels of these pyroles are associated with an increased demand for vitamin B6 and zinc. One hypothesis is that pyroles combine irreversibly with vitamin B6 and zinc, resulting in their excretion resulting in a severe deficiency of these nutrients. Others suggest an association between high levels of pyroles, oxidative stress and increased demand for vitamins B3, B6 (P-5-P) and zinc. The Pfeiffer Institute suggests the syndrome is stress induced. Pyroluria is often found in individuals with ADHD, schizophrenia, alcoholism, bipolar disorder and depression. Read more about pyroluria here.

GUT DYSFUNCTION & GASTROINTESTINAL PARASITES

Significant quantities of potential bacterial pathogens are found in almost every child with ADHD. One study found significant quantities of bacterial pathogens, yeast organisms and protozoan parasites were in a high proportion of children with ADHD.  These findings are quite suggestive that these children suffer from impairment of gut mucosal immunity. Read more about how we can test for gut dysfunction, dysbiosis and parasites here.

ENVIRONMENTAL TOXINS

Lead, organophosphate pesticides, chlorinated hydrocarbons, carbon disulphide, solvents and mercury have been identified as causing a problem. Numerous studies have demonstrated the neurotoxicity of lead, even low-level exposure has been implicated in impaired cognitive function as well as behavioural and attention disorders. Lead appears to interfere with a calcium-mediated intracellular messenger system and neurotransmission. Increased lead absorption has been linked to deficient calcium, iron and zinc status.

Exposure to mercury can cause immune, sensory, neurological, motor and behavioural dysfunction. The ethylmercury containing preservative thiomersol used in vaccines and only recently removed from most but not all vaccines, has been suspected of causing problems in susceptible children. High levels of other heavy metals including aluminium, cadmium, arsenic, antimony, etc have been associated with learning and behavioural difficulties.

SLEEP

Sleep-disordered breathing (SDB) ranging from snoring to obstructive sleep apnea, is associated with a higher prevalence of behavioural problems in children. Children with SDB were significantly more likely to show a higher prevalence of problems, including emotional lability, hyperactivity, aggressive behaviour and social problems.

Read more about this topic in these ADHD studies:

Parent-reported sleep problems, symptom ratings, and serum ferritin levels in children with attentiondeficit/hyperactivity disorder: a case control study.

Increased behavioral morbidity in school-aged children with sleep-disordered breathing.

OUTDOOR EXPOSURE

Symptoms such as inattention and impulsivity are reduced after exposure to natural views or settings (outdoor play essentially). Exposure to natural settings in the course of common after-school and weekend activities may be widely effective in reducing ADHD symptoms in children. Encouraging children to spend more time outdoors is an inexpensive, widely accessible treatment that is also free of side effects.

(JCM – Journal Digest Supplement, March/April 2005.)

Besides the literature listed here, we encourage you to read up on as many ADHD studies as you can.

Reviewed by John Pietryka 30 June 2017 references
  • current version

  • PEER REVIEWER

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  • next review

This document has been developed and peer reviewed by a KIDS HEALTH Advisory Board Representative and is based on expert opinion and the available published literature at the time of review. Information contained in this document is not intended to replace medical advice and any questions regarding a medical diagnosis or treatment should be directed to a medical practitioner.

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ADD and ADHD Studies: A Comprehensive Review of the Literature

It’s normal to feel helpless or overwhelmed when you are the parent or guardian of a child with ADD or ADHD. Besides having a good relationship and communication with your doctors, however, one of the best things you can do is to arm yourself with knowledge. Luckily, there are a lot of ADD and ADHD studies available to the public.

What is ADHD?

Attention Deficit Hyperactivity Disorder (ADHD), previously known as hyperkinesis, is the most common behavioural disorder in children. It is estimated to affect 3 to 5 percent of school-age children. Frequently, the symptoms of ADHD appear together with learning problems, oppositional conduct disorder, anxiety, and depression.

Relatives of children with ADHD also have a higher incidence of neuropsychiatric disorders than relatives of families with no ADHD children. Conduct disorder, oppositional defiant disorder, major affective disorder (depression or bipolar disorder), anxiety disorder, including obsessive-compulsive disorder, and Tourette syndrome are seen more often in relatives of children with ADHD. Teenagers with ADHD, particularly untreated ADHD, are at risk for drug and alcohol abuse.

There are more boys than girls diagnosed with ADHD. Girls usually do not manifest disruptive behaviours to the extent seen in boys; girls with ADHD have half of the rates of conduct disorder and oppositional defiant disorder but are much more likely to have significant social problems. Compared with boys with ADHD, they manifest more emotional distress, have higher rates of depression and anxiety, are highly vulnerable to stress, and have poor self-esteem and a limited sense of control.

Here are ADHD studies regarding this topic:

Childhood ADHD and risk for substance dependence in adulthood: a longitudinal, population-based study.

The potential for misuse and abuse of medications in ADHD: a review.

When is ADHD not ADHD?

Some parents and teachers prefer children to be diagnosed with ADHD, if it means a pill can improve their behaviour. Claims of misdiagnosis are not uncommon. There are claims that a brief consultation with a doctor is insufficient time to be able to accurately diagnose ADHD in a child. A proper diagnosis requires a lengthy assessment with a behavioural specialist. Some children exhibit ADHD like symptoms and are mistakenly diagnosed as having ADHD.

Some other conditions that should be considered as affecting children’s behaviour are listed below:

  • Some children may have learning difficulties or dyslexia and dyscalculia (a specific learning disability in mathematics) and are often mistakenly diagnosed as inattentive ADHD
  • Auditory processing disorder
  • Oppositional defiance disorder
  • Epilepsy (an electroencephalogram is required to detect any epileptiform abnormalities), specifically absence seizures
  • A family history of Restless Legs Syndrome (RLS) is common in these children. Periodic limb movements in sleep may directly lead to symptoms of ADHD due to sleep disruption. Thus, when a child presents with symptoms of hyperactivity, inattention, irritability, and growing pains, the differential diagnosis and workup should include RLS in addition to ADHD. (Case 2: A 6-Year-Old Boy Who “Can’t Sit Still” Medscape Neurology & Neurosurgery. 2005; 7 (1): ©2005 Medscape)
  • Sleep disordered breathing
  • Exposure to caffeinated cola drinks impairs children’s learning ability by causing restlessness, hyperactivity, and inattention. Caffeine intake should be assessed as part of the evaluation. (Caffeinated Colas Linked to Inattention, Hyperactivity in First-Grade Children 2005 APA Annual Meeting: Abstract NR45. Presented May 23, 2005.)
  • In children with tics and obsessive/compulsive behaviours, including oppositional defiant behaviours, the possibility of Paediatric Autoimmune Neurodevelopmental Disorder Associated with Streptococcus infections (PANDAS) should be considered. This is a medical condition in which autoimmune antibodies to group A beta haemolytic streptococcus can in some children affect brain function, causing obsessive-compulsive disorder or symptoms of cognitive inflexibility, tics and ADHD.

SIGNIFICANCE OF PREGNANCY OUTCOMES

Intrauterine growth retardation is a risk factor for ADD/ADHD. Smoking is a major cause of growth retardation.

Very low birth weight may have severe cognitive impairment (25%), increased ADHD, and up to 60% need assistance at school and require special education. Birth trauma has been associated with increased incidence of ADHD.

OTITIS MEDIA – Chronic Ear Infections

  • Greater incidence of ADHD
  • Increased distractibility later in life
  • Lower IQ scores, poor performance on tests of reading, spelling, math, increased attention deficits, and increased behaviour problems at school
  • http://www.ncbi.nlm.nih.gov/pubmed/19037954
  • http://www.ncbi.nlm.nih.gov/pubmed/2304807

HEAVY METAL TOXICITY

Heavy metals, like mercury, copper, lead and aluminium, also inhibit neurotransmitter pathways and can interfere with the binding of the neurotransmitters with their receptors. Read more about heavy metal testing utilising a hair sample here.

FOOD SENSITIVITIES

Food sensitivities, artificial colours and flavours, and excessive phosphate ingestion seem to be an important causative factor in this disorder. Food sensitivities and food allergy provoke hyperactivity through partially digested food proteins (exorphins) entering the blood stream and scrambling the neuronal communicative system. In eight out of nine studies 86% of hyperactive children had elevated blood eosinophils, indicative of allergy or parasitic infection.

Artificial colours, flavours and preservatives inhibit a number of detoxifying enzymes (e.g. aryl sulphatase, catechol-o-methyl transferase), which increases the toxic effects of certain foods. Studies have linked ingestion of artificial food colourings and behavioural change in children. Irritability, restlessness and sleep disturbance have been specifically linked to food colourings such as tartrazine.

The most common chemicals children react to are amines, salicylates, artificial colours, glutamates and preservatives. Statistically significant improvements in conduct, learning, impulsivity and hyperactivity have been demonstrated if these are removed or minimised in the diet. Data from two double blind studies indicate that 73-76% of ADHD children respond favourably to food elimination diets. Maintenance on low-antigen diets raised the success rate to 82%.  

Calcium propionate (preservative code 282) is a colourless, tasteless and odourless preservative used in breads to discourage mould growth. Researchers in Darwin investigated the effects of 282 on behaviour on children with “behavioural problems”. The authors concluded that; the preservative may cause restlessness, inattention, irritability and sleep disturbance in some children.

ALTERED BRAIN GLUCOSE METABOLISM

Correct glucose metabolism in the brain is important for efficient cognitive function. Studies showing differences in brain glucose metabolism between ADHD patients and normal subjects, ADHD patients show 8.1% lower levels of brain glucose metabolism. Studies of diabetic children show significantly reduced attention, both at mild hypoglycaemia and also low normal blood glucose levels.

NEUROTRANSMITTERS

ADHD can be considered a disorder of neurotransmitter function, with particular focus on the neurotransmitters dopamine and serotonin.

DOPAMINE

Dopamine is the neurotransmitter that regulates the system that plays an important function in learning, motivation, goals, drives, and emotion, all of which are crucial to survival. There has been extensive research conducted that demonstrates that dopamine is critical in the regulation of learning, as well as maintaining trained or conditioned responses and motivated (goal-directed) behaviours. Dopamine also plays an important role in working memory, the ability to “keep something in mind” for a brief period of time.

A reduction of dopamine activity can cause diarrhoea, irritable bowel syndrome, cramps, nervous stomach, increased saliva, and raised insulin levels, and airways and cerebral blood vessels constrict. There may be faulty neurotransmission of dopamine, due to genetic variations of the dopamine receptor or a problem with dopamine re-uptake at the nerve junctions. This causes poor dopamine communication between neurons.

(The Nervous System. Henry Osiecki)

SEROTONIN

Serotonin is a neurotransmitter that has a calming effect on the brain. Low serotonin levels have been identified in ADHD, particularly in boys with aggressive symptoms. Increasing serotonin levels through appropriate supplementation has been shown to reduce aggressive symptoms.

In 1999, researchers at the Howard Hughes Medical Institute discovered that Ritalin and other stimulants exert their paradoxical calming effects by boosting serotonin levels in the brain. Elevating serotonin appears to restore the delicate balance between dopamine and serotonin and calms hyperactivity. Previously it was thought that the calming action of Ritalin worked through the neurotransmitter dopamine. From these results it was suspected that dopamine wasn’t the only key to understanding ADHD.  Their studies suggested that rather than acting directly on dopamine, the stimulants create a calming effect by increasing serotonin levels. The study concluded that the proper balance between dopamine and serotonin was the key, and that hyperactivity may develop when the relationship between dopamine and serotonin is out of balance.

PYROLURIA

Pyrolurias a genetic weakness where there is decreased activity of one of the enzymes involved in haemoglobin synthesis. This can result in abnormal haemoglobin synthesis and cause excess production of a by-product called kryptopyrrole. It has been suggested that pyroluria is heavily connected to certain mood disorders. Patients with high kryptopyrroles in their urine may present with severe mood swings, poor memory and explosive temper, may show signs of vitamin B6, B3 and zinc deficiency.

Some researchers report that high levels of these pyroles are associated with an increased demand for vitamin B6 and zinc. One hypothesis is that pyroles combine irreversibly with vitamin B6 and zinc, resulting in their excretion resulting in a severe deficiency of these nutrients. Others suggest an association between high levels of pyroles, oxidative stress and increased demand for vitamins B3, B6 (P-5-P) and zinc. The Pfeiffer Institute suggests the syndrome is stress induced. Pyroluria is often found in individuals with ADHD, schizophrenia, alcoholism, bipolar disorder and depression. Read more about pyroluria here.

GUT DYSFUNCTION & GASTROINTESTINAL PARASITES

Significant quantities of potential bacterial pathogens are found in almost every child with ADHD. One study found significant quantities of bacterial pathogens, yeast organisms and protozoan parasites were in a high proportion of children with ADHD.  These findings are quite suggestive that these children suffer from impairment of gut mucosal immunity. Read more about how we can test for gut dysfunction, dysbiosis and parasites here.

ENVIRONMENTAL TOXINS

Lead, organophosphate pesticides, chlorinated hydrocarbons, carbon disulphide, solvents and mercury have been identified as causing a problem. Numerous studies have demonstrated the neurotoxicity of lead, even low-level exposure has been implicated in impaired cognitive function as well as behavioural and attention disorders. Lead appears to interfere with a calcium-mediated intracellular messenger system and neurotransmission. Increased lead absorption has been linked to deficient calcium, iron and zinc status.

Exposure to mercury can cause immune, sensory, neurological, motor and behavioural dysfunction. The ethylmercury containing preservative thiomersol used in vaccines and only recently removed from most but not all vaccines, has been suspected of causing problems in susceptible children. High levels of other heavy metals including aluminium, cadmium, arsenic, antimony, etc have been associated with learning and behavioural difficulties.

SLEEP

Sleep-disordered breathing (SDB) ranging from snoring to obstructive sleep apnea, is associated with a higher prevalence of behavioural problems in children. Children with SDB were significantly more likely to show a higher prevalence of problems, including emotional lability, hyperactivity, aggressive behaviour and social problems.

Read more about this topic in these ADHD studies:

Parent-reported sleep problems, symptom ratings, and serum ferritin levels in children with attentiondeficit/hyperactivity disorder: a case control study.

Increased behavioral morbidity in school-aged children with sleep-disordered breathing.

OUTDOOR EXPOSURE

Symptoms such as inattention and impulsivity are reduced after exposure to natural views or settings (outdoor play essentially). Exposure to natural settings in the course of common after-school and weekend activities may be widely effective in reducing ADHD symptoms in children. Encouraging children to spend more time outdoors is an inexpensive, widely accessible treatment that is also free of side effects.

(JCM – Journal Digest Supplement, March/April 2005.)

Besides the literature listed here, we encourage you to read up on as many ADHD studies as you can.

Reviewed by Lisa Kelly 30 June 2017
references
  • current version

  • PEER REVIEWER

  • Doc id

  • next review

This document has been developed and peer reviewed by a KIDS HEALTH Advisory Board Representative and is based on expert opinion and the available published literature at the time of review. Information contained in this document is not intended to replace medical advice and any questions regarding a medical diagnosis or treatment should be directed to a medical practitioner.

make a comment

0 comments

more articles by John Pietryka

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latest articles

view more

MEET THE EXPERTS

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