Is Histamine and Not Acetylcholine the Missing Link between ADHD and Allergies? Speer Allergic Tension Fatigue Syndrome Re-Visited

Abstract

Speer allergic tension-fatigue syndrome (SATFS) is a classic allergy syndrome characterized by allergy-like symptoms, muscle tension, headaches, chronic fatigue, and other particular behaviors that were initially described in the fifties. The particular behaviors displayed include symptoms such as hyperkinesis, hyperesthesia (i.e., insomnia), restlessness, and distractibility, among others. Interestingly, these symptoms are very similar to descriptions of attention deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder worldwide, which is characterized by inattention, hyperactivity, and impulsivity. The clinical description of SATFS precedes the nomination of ADHD in 1960 by Stella Chess. In this conceptual paper, we stress that there is a gap in the research on the relationship between ADHD and allergic pathologies. The hypotheses of this conceptual paper are (1) SATFS is probably one of the first and best historical descriptions of ADHD alongside a common comorbidity (allergy) displayed by these patients; (2) SATFS (ADHD) is a systemic disease that includes both somatic and behavioral manifestations that may influence each other in a bidirectional manner; (3) The role of neuroinflammation and histamine is key for understanding the pathophysiology of ADHD and its frequent somatic comorbidities; (4) The deficiency of the diamine oxidase (DAO) enzyme, which metabolizes histamine extracellularly, may play a role in the pathophysiology of ADHD. Decreased DAO activity may lead to an accumulation of histamine, which could contribute to core ADHD symptoms and comorbid disorders. Further empirical studies are needed to confirm our hypotheses.

Prevalence and Clinical Picture of Diamine Oxidase Gene Variants in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study

“…Finally, our results give some support to our hypothesis that DAO deficiency, an enzyme which metabolizes histamine extracellularly, might play a critical role in the pathophysiology of ADHD. Thus, decreased DAO activity might lead to an accumulation of histamine, which could explain both ADHD symptoms and comorbid disorders, such as atopy [ 14 ].…”

“…To sum up, our findings are in keeping with the literature linking DAO deficiency with migraine and other medical disorders typically included within the HIT picture. Given that our sample was composed of patients with a primary diagnosis of ADHD, that most of them displayed at least one AOC1 variant related to DAO deficiency, and that some medications approved for the treatment of ADHD (i.e., lisdexamfetamine dimesylate) may improve DAO activity [ 43 ], thus helping to decrease blood histamine levels, we may conclude that some medications for ADHD may help to reduce both ADHD and HIT symptoms by killing two birds with one shot [ 14 ]. Another interesting finding was between variant 2 (rs1049742) and binge eating disorder.…”

“…Accordingly, we may only speculate about the reasons behind our finding. Histamine in the CNS is involved in learning and memory, and treatment with antihistamines characteristically impairs learning and memory (see [ 14 ] for a review of the role of each histamine receptor in the brain). A basic study demonstrated the critical role of histamine in long-term memory by providing the brain with the compensatory plasticity necessary to ensure memorization of emotionally salient events when one brain structure is compromised [ 45 ].…”

“…Indeed, two novel mutations in the human HNMT gene (G179A and T632C) impairing its enzymatic activity had been associated with intellectual disability [ 47 ]. However, as explained elsewhere [ 14 ], blood histamine does not pass the blood–brain barrier (BBB), and therefore, DAO deficiency should not influence brain functioning. However, the BBB is permeable to histamine during development.…”

“…Furthermore, most of these disorders are usually included within a relatively unknown entity, histamine intolerance (HIT). A recent study postulated that histamine might be the missing link between ADHD and medical comorbidities usually included within Allergic Tension Fatigue Syndrome [ 14 ].…”