shared genetic background in attention deficit hyperactivity disorder and narcolepsy 2020


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Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy
Translational Psychiatry volume 10, Article number: 284 (2020) Cite this article


Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients.

Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions.

Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use).

However, the common biological mechanism for these disorders has not been well understood.

Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual.

We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876).

Gene-set enrichment analyses were used to identify common pathways underlying these disorders.

Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold < 0.05, β [SE], 5.815 [1.774]; P = 0.002) and inattention domain (e.g., P-value threshold < 0.05, β [SE], 5.734 [1.761]; P = 0.004).

However, EHS PRS was not significantly associated with either domain of ADHD traits.

Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy.

Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship.

Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.


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Another scientist answered to this publication! 2021

Genetic links between narcolepsy and ADHD
Translational Psychiatry volume 11, Article number: 333 (2021) Cite this article

Dear Editor,
In a recent issue of Translational Psychiatry, Takahashi et al.1 reported their analysis of shared polygenic risk scores suggest a shared genetic background for both attention deficit hyperactivity disorder (ADHD) and narcolepsy. By another method, we described a similar association between ADHD and narcolepsy. In a paper delivered at the 1995 American Academy of Neurology2, we reported three families each in two generations with concurrent ADHD, hypersomnia defined by pupillometry3 without sleep log evidence of sleep disorder and both HLA markers DR-2/DQw-1 employed at that time associated with narcolepsy (Fig. 1).
Fig. 1

HLA typing using DR-2/DQw-1 markers, hypersomnia, ADHD ± Reading Disorder in two generations.

Our subsequent studies have suggested a frequency of HLA markers associated with narcolepsy more than double than anticipated in Caucasians in individuals with behavioral and cognitive evidence of ADHD4.

Clinically, we have observed late adolescent ADHD patients who will not drive automobiles without their alerting medications for fear of falling asleep.

We have additionally observed an increased frequency of these HLA markers as well as hypersomnia in individuals with dyslexia, both with and without ADHD5. However, either condition may occur independent of these HLA markers.

The social significance of such an association if valid is that an unknown percentage of ADHD children/adolescents/adults may require alerting medication to become safe adult drivers, as sleepiness increases the risk of motor vehicle accident by a factor of 2.56.


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Another scientist made the link in 2020

Published online 2020 Jun 4. doi: 10.7759/cureus.8436
PMCID: PMC7336577
PMID: 32642351

Attention-Deficit/Hyperactivity Disorder Patients May Have Undiagnosed Narcolepsy
Monitoring Editor: Alexander Muacevic and John R Adler


Attention-deficit/hyperactivity disorder (ADHD) patients have many comorbidities. Narcoleptic patients have a big prevalence of ADHD (15%-30%). Both groups suffer from similar symptoms and benefit from the same class of medications. As such, narcolepsy could be masked in ADHD patients.

Low serum ferritin has been found both in ADHD patients as well as in patients with narcolepsy.

Materials & methods
We enrolled 26 participants (14 ADHD patients and 12 controls). They answered several questionnaires, and blood samples were obtained from 20 participants. We had clear exclusion criteria.

Using the Ullanlinna Narcolepsy Scale (UNS), we identified 3 possible narcolepsy patients within the ADHD group (14 patients) and no suspects in the control group.

There was a statistically significant negative correlation between serum iron levels and ADHD symptom severity.
No correlation was found measuring serum ferritin levels.

Narcolepsy may be more common within ADHD patients than in the general population.

Some of these patients could benefit from a change in medication.

Low serum iron and ferritin levels could be relevant in ADHD pathophysiology. This requires further exploratory research.


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(I only read the header above.) Research has made an association between adhd and inflammation. For example there is an association between autoimmune disease ankylosing spondylitis and adhd.

perchance dreamer

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Narcolepsy is sometimes a result of brain injury. For many people, it's a lifelong condition, but I developed narcolepsy as an adult after an accident, and years later, I recovered from it. I'm so glad I no longer have narcolepsy, but I do kind of miss the sleep hallucinations.