December 17, 2021
A team of Spanish researchers performed a systematic search of the medical literature and found 28 studies that could be included in a series of meta-analyses of specific measures of sleep impairment. Except for a single meta-analysis with eight studies and 1,713 participants, however, all involved just three to five studies apiece, with anywhere from 121 to just over a thousand participants.
The team examined three sorts of measures:
· Subjective measures, based on self-reporting by ADHD patients.
· Polysomnography is an objective sleep study in which the subject is wired up and studied by technicians in a lab, usually overnight, monitoring multiple body functions, such as brain activity, eye movements, muscle activation, and heart rhythm.
· Actigraphy, a non-invasive objective means of monitoring sleep. The subject wears an actimetry monitor, which is usually worn like a wristwatch on the non-dominant arm. Because it is minimally intrusive, the subject may wear it for a week or more while engaging in normal activities.
In the subjective measures, adults with ADHD generally reported substantially higher sleep impairments than non-ADHD controls. In the largest meta-analysis, covering eight studies and 1,713 participants, adults with ADHD reported moderately longer latency times for falling asleep than controls. In meta-analyses of five studies with between 834 and 1,130 participants, they also reported moderately poorer sleep quality, more frequent night awakenings, being moderately less rested upon awakening in the morning, and moderate-to-strongly greater daytime sleepiness. There was no significant difference in perceived sleep duration.
Polysomnography measures, on the other hand, failed to confirm these subjective impressions. No significant differences were found between adults with ADHD and controls for the initial latency period until onset of sleep, sleep efficiency, waking after the onset of sleep, total sleep time, stage one or stage two sleep, slow-wave sleep, REM (rapid eye movement) sleep, and latency period until REM sleep.
As mentioned above, polysomnography is conducted in lab settings, and therefore inevitably diverges from normal patterns of behavior. Actigraphy helps bridge that gap, by monitoring normal behavior, though with more limited types and precision of data analysis.
And indeed, a meta-analysis of four studies with 222 participants confirmed self-reports that sleep efficiency was moderate to strongly lower in adults with ADHD and that the latency period until the onset of sleep was markedly longer. On the other hand, it found no significant difference in true sleep.
The researchers also looked at prevalence statistics. Whereas the prevalence of sleep-onset insomnia in the general population has been reported in the range of 13 to 15 percent, a meta-analysis of four studies with 466 participants found fully two-thirds of adults with ADHD reporting insomnia, a greater than four-to-one ratio. Similarly, a meta-analysis of three studies with 458 participants found one-third reporting daytime sleepiness, which is twice the rate reported in the general population.
There was no sign of publication bias in any of these results. The authors cautioned, however, about the small number of studies involved, stating this "compromises the generalizability of the findings." Also, some studies included patients undergoing pharmacological treatment for ADHD, "increasing the risk of confounding results."
Moreover, "Sleep onset latency and sleep efficiency were not significantly impaired in the polysomnography, which was incongruent with the actigraphy results. This may be due to a difference in the evaluation context. Whereas polysomnography is considered the gold-standard measure to objectively assess sleep architecture, actigraphy shows a more ecological approach, with the evaluation being conducted in a more naturalistic context for a longer period. However, actigraphy has more environmental influence, which can compromise the data recorded and the interpretation of the results, whereas, in polysomnography, multiple variables can be controlled in the laboratory setting to increase the internal validity of the results. On the contrary, polysomnography studies can produce artifacts due to the unusual circumstances in the setting, so results may need to be interpreted with caution."
The authors concluded, "The results found in the present study show the relevance of addressing sleep concerns in adult populations diagnosed with neurodevelopmental conditions."
Jorge Lugo, Christian Fadeuilhe, Laura Gisbert, Imanol Setiena, Mercedes Delgado, Montserrat Corrales, Vanesa Richarte, Josep Antoni Ramos-Quiroga, "Sleep in adults with autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis," EuropeanNeuropsychopharmacology (2020),https://doi.org/10.1016/j.euroneuro.2020.07.004.
A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD).
A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by:
Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings.
The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding.
Almost 186,000 of these children were exposed to acetaminophen during pregnancy.
After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed.
However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication. High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage.
Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.
The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.”
Antipsychotic medications are used to treat a variety of psychiatric disorders, including schizophrenia, bipolar disorder, sleeping problems, major depression, and severe anxiety.
Untreated maternal mental illness is associated with poor health outcomes for both mothers and their offspring. On the other hand, one must guard against any potential direct harms of medications on development – including neurological development – of the fetus.
Because prenatal use of antipsychotics is infrequent, previous observational studies have suffered from small sample sizes that have not enabled precise and reliable assessment of risk. The clinical decision about whether to continue antipsychotic treatment in patients who become pregnant has therefore remained inconclusive.
In search of more reliable guidance, an international study team conducted a systematic search of the peer-reviewed medical literature to perform the first meta-analysis on this topic.
They evaluated study quality and only included studies rated “good” or better.
Identification of ADHD was determined by clinical diagnosis.
Meta-analysis of four studies encompassing over eight million participants found a slight association. Children exposed to maternal antipsychotics during pregnancy were 11% more likely to be diagnosed with ADHD subsequently.
But even in observational studies with millions of participants, such associations – especially when slight to begin with – could be due to unmeasured confounders.
The team therefore compared children with gestational exposure to siblings from the same mother who were not exposed, to address shared genetic and social factors at the family level.
Meta-analysis of two population-based sibling-matched studies with a combined total of over 4.6 million participants in Denmark, Norway, Sweden, Finland, Iceland, and Hong Kong found no significant association between gestational exposure to antipsychotic medications and subsequent diagnosis of ADHD.
The team concluded, “Our systematic review and meta-analysis of observational studies indicates that the heightened risks of ADHD and ASD observed in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relation to the antipsychotic itself.”
Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time.
An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107 children who have been followed up every two years since birth.
The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.
Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year.
The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ).
Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10.
With a diagnosis of ADHD at age 10 and all other factors held constant:
Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect.
Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes.
The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.”
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