In a recent study published in Nutrients, researchers investigated the risk of Attention Deficit/Hyperactivity Disorder (ADHD) among glucose 6-phosphate dehydrogenase (G6PD)-deficient individuals.
Study: The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder. Image Credit: ClareM/Shutterstock.com
Background
Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition that affects children and adults across the globe. The disorder is inheritable; however, etiopathogenesis is complicated, with scientific evidence that inflammatory processes interact with genomic risk in ADHD development.
A fascinating but under-researched area of inquiry also links the immunological-inflammatory pathways to oxidative stressors in ADHD development.
G6PD is an enzyme that aids in forming glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH), which are necessary for the oxidation-reduction balance of the body. G6PD deficiency leads to reduced GSH levels and increased oxidative stress.
Deficiency of G6PD, which is more frequent in Mediterranean populations, is a commonly observed enzymopathy that may be related to ADHD.
About the study
In the present population-based, retrospective cohort study, researchers investigated whether G6PD deficiency increases ADHD risk.
The team analyzed the clinical variables of 7,473 G6PD-deficient individuals (cases) and 29,892 non-G6PD-deficient controls (1:4 case: control ratio) extracted from the electronic health records (EHS) of the Leumit Health Services (LHS) members (n=1,031,354).
The controls matched in age, sex, ethnicity, socioeconomic status, geographical region, and calendar year of the first visit documented in LHS records compared to cases.
The researchers analyzed data obtained from only those individuals the LHS insured for two or more years before the data extraction date. The team extracted information on demographics, smoking habits, body mass index (BMI), clinical parameters, blood pressure (BP), laboratory investigations, and international classification of diseases, ninth version (ICD-9) codes from LHS records.
Individuals with G6PD levels below 4.0 U/g Hg were G6PD-deficient. The team diagnosed ADHD using the Israeli Ministry of Health guidelines, the Diagnostic and Statistical Manual, and the fourth or fifth version (DSM-IV or V) criteria.
Socioeconomic status was classified following the Israeli Central Bureau of Statistics guidelines. The team compared the utilization of healthcare resources among 1,040 individuals diagnosed with ADHD in the case group with the 3,650 individuals who received an ADHD diagnosis in the control group.
Fisher’s exact and Mann-Whitney U tests were used for categorical and continuous variables, respectively.
Results
The mean participant age was 29 years, 69% were male, and the mean follow-up duration was 14 years. Deficiency of G6PD was related to significantly elevated risks of ADHD development [odds ratio (OR) of 1.2], seeking neurologist care (OR, 1.3), and psychiatrist consultations (OR, 1.1).
Stimulant medication usage among individuals deficient in G6PD was significantly higher, by 17%, for methylphenidate medications (OR, 1.2).
In addition, a 16% higher risk of amphetamine usage (OR, 1.2) was observed among cases compared to controls. G6PD deficiency occurred among 1,040 (14%) case group and 3,650 (12%) control group individuals.
Individuals deficient in G6PD were more likely to be non-smokers (OR, 1.1) and non-diabetic (OR, 0.9). The number of neurologist consultations per ADHD patient was higher among cases (3.6 consultations) compared to controls (3.1 consultations).
ADHD and G6PD deficiency are interlinked through various mechanisms. G6PD deficiency is associated with oxidative stress, which can lead to hemolytic anemia and result in neurological and behavioral disorders. G6PD is involved in producing NADPH, which is crucial for synthesizing neurotransmitters such as serotonin and dopamine.
G6PD deficiency may disturb the equilibrium of these neurotransmitters, contributing to ADHD development. Elevated reactive oxygen species (ROS) levels could lead to inflammation, heightening infectious disease symptomatology.
Studies have reported that ADHD patients have a higher risk of infections, including coronavirus disease 2019 (COVID-19), and a higher rate of severity and consequences. G6PD deficiency may be an additional factor that exacerbates existing ADHD symptoms.
Conclusions
Overall, the study findings showed that individuals deficient in G6PD have an increased risk of developing ADHD and more frequent adult psychiatrist and neurologist consultations than controls.
The study findings follow those observed for the relationship between Attention Deficit/Hyperactivity Disorder and infectious diseases, between Attention Deficit/Hyperactivity Disorder and inflammatory-type and somatic conditions, and between COVID-19, immunological disorders, and G6PD deficiency.
However, due to the retrospective and observational study design, potential confounding variables may impact the association.
Further studies, including prospective study designs and more diverse populations, are required to determine causal associations between G6PD deficiency and ADHD risk and elucidate underlying biological mechanisms.
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