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There have been indications that infants who have difficulty sleeping are more likely to later develop ADHD in childhood. Would this hold up in a large nationwide cohort study?

Noting that "Norway has several national health registries with compulsory and automatically collected information," and "registries can be linked on an individual level, making it possible to conduct large cohort studies," a Norwegian team of researchers studied the association between sleep-inducing medications prescribed to infants under three years old and diagnoses of ADHD between the ages of five and eleven.

Norway has a national health insurance system that covers all residents, and pays in full for youths under 16 years old. Norwegian pharmacies must register all dispensed prescriptions into a national register as a prerequisite for reimbursement.

The study included all children born in Norway from 2004 through 2010, minus those who died or emigrated, leaving a total of 410,555 children.

In addition to traditional hypnotic and sedative drugs and melatonin, the study looked at antihistamines, which though intended for respiratory use, are frequently used for gentle sedation.

The two most frequently prescribed drugs were found to be dexchlorpheniramine (girls 7%, boys 8%) and trimeprazine(girls 3%, boys 4%), both of which are antihistamines.

After adjusting for parental education as an indicator of family socioeconomic status, and parental ADHD as indicated by prescription of ADHD medications, girls who had been prescribed sleeping medications on at least two occasions were twice as likely to subsequently develop ADHD, and boys about 60 percent more likely. For, dexchlorpheniramine equivalent associations were not statistically significant for either boys or girls. But girls prescribed trimeprazine on at least two occasions were almost three times as likely to subsequently develop ADHD, and boys were well over twice as likely.

A limitation of the study was that there was no direct data for sleep diagnosis. The authors noted, "The Norwegian prescription database does not contain diagnosis unless medications are reimbursed and hypnotics are not reimbursed for insomnia or sleep disturbances in general. Sleep diagnoses were also not available from the Norwegian Patient Registry, as there seems to be a clinical tradition for not using the ICD- 10G47 Sleep Disorders diagnosis for children."

The authors concluded, "It has previously been shown that infant regulation problems, including sleep problems, are associated with ADHD diagnosis. We replicate this finding in a large cohort, where continuous data collection ensures no recall bias and no loss to follow-up. We find that the use of hypnotic drugs before 3 years of age, signifying substantial sleeping problems, increases the risk of a later ADHD diagnosis. This was especially true for the antihistaminic drug, trimeprazine."

Both Taiwan and Sweden have universal single-payer health insurance systems that in effect track their entire national populations. With detailed health and other records on millions of individuals, with no significant exclusions, one can essentially eliminate sampling error, and also explore how associations vary by degree of familial/genetic relationship.

A Taiwanese research team used the Taiwan National Health Insurance Research Database to follow 708,517 family triads (father-mother-child) from 2001 through 2011. That's a total of over 2.1 million persons. The database covers over 99% of Taiwan's population.

Noting that previous studies had found links between maternal autoimmune diseases and ADHD in their offspring and that research on associations with paternal autoimmune diseases had been inconclusive, they were particularly interested in exploring the latter.

Children born from 2001 through 2008 were enrolled in the study. The investigators then noted the presence or absence of any autoimmune disease in their parents from 1996 through childbirth.

In Taiwan, expert panels review diagnostic information of severe systemic autoimmune diseases to confirm the diagnosis. Once confirmed, patient co-payments are waived. ADHD diagnoses are by board-certified psychiatrists.

To reduce the effect of confounding variables, adjustments were made for family demographic data (income level and residence), parental ages, parental mental disorders, and sex of children.

The presence of any maternal autoimmune diseases was associated with a 60% greater risk of ADHD in offspring. The risk was especially elevated for inflammatory bowel diseases (2.4 times the risk) and ankylosing spondylitis (twice the risk).

The presence of any paternal autoimmune diseases was also associated with an elevated risk of ADHD in offspring, although only about half as much as for maternal autoimmune diseases, with a 33% greater risk overall. The association was especially pronounced for psoriasis and ankylosing spondylitis, both doubling the risk of ADHD in offspring.

Meanwhile, half a world away, a joint Swedish, Norwegian, and U.S. team used the Swedish national registries to dig further into these associations. They did this by examining data not only from mothers and fathers, but from full siblings, aunts, uncles, and cousins as well, to probe genetic links.

The team used the Swedish registers to identify 5,178,225 individuals born in Sweden between 1960 and 2010 for whom the identity of the biological mother was known, excluding all who died or emigrated before age 10. They then used the registers to identify the aforementioned relatives.

The researchers only included autoimmune diseases with at least two thousand diagnosed individuals in the cohort, to avoid small sample effects.

They adjusted for sex and year of birth, but not "for another covariate that is often adjusted for (e.g. maternal education, family income, parental psychiatric disorder, parental AD [autoimmune disease] as these are likely not true confounders of the association between ADHD and ADD, but may rather represent either mediator between ADHD and AD's, or proxies of ADHD and/or AD risk or alternatively proxies for the associations we aim to measure."

The team found statistically significant associations between ADHD and autoimmune diseases in all categories of relatives. Mothers of children with ADHD were 29% more likely to have an autoimmune disease than those of typically developing children; fathers were 14% more likely to have an autoimmune disease; full siblings 19% more likely; aunts 12% more likely; uncles 7% more likely; and cousins 4% more likely.

Quantitative genetic modeling produced a significant genetic correlation, but no significant environmental correlation. Genetic correlation explained most, if not all, the covariance between ADHD and any autoimmune disease.

The authors concluded, "ADHD was to some degree more strongly associated with maternal than paternal AD's, but by using aunts and uncles in a genetically informative study design, we demonstrate that this difference cannot be readily explained by AD-mediated maternal effects. Quantitative genetic modeling further indicates that the familial co-aggregation of ADHD and ADs is partly due to shared genetic factors. In addition, biological aunts, uncles, and cousins must be assumed to share the little environment with the index individuals, in further support of shared genetic factors underlying the familial co-aggregation. Moreover, both epidemiological and molecular genetics studies have demonstrated positive genetic correlations between ADHD and ADs, in agreement with our findings."

The authors emphasize that these results do not warrant screening for autoimmune diseases among asymptomatic individuals with ADHD.

The National Longitudinal Survey of Children and Youth is a prospective cohort of Canadian children followed from childhood to early adulthood. It is considered nationally representative, except for children living on First Nations (indigenous) reserves, in institutions, and in remote regions. Keep in mind that suicide rates among indigenous youth are way higher than in the general population.

The initial cohort included 8,698 participants aged 7- 11 years, of which 6,465 had to be excluded for lack of answers to questions on suicide attempts, leaving 2,233 participants. Again, by comparison with the excluded group, these participants were less likely to be from higher-risk backgrounds, including having a mother who did not complete high school or coming from low-income families.

The share of adolescents who attempted suicide in the previous year increased from 3.6% at ages 12-13 years to 5.6% at ages 14-15 years, then gradually declined to 1% of young adults at ages 22-23 years.

The overwhelming majority (96%)reported never attempting suicide. One in fifty (2%) reported suicide attempts limited to adolescence, and another one in fifty reported suicide attempts persisting into adulthood.

The study team performed a multivariable regression model examining the contributions of sex and ten risk factors, including various psychiatric disorders, for suicidality. One of those risk factors was ADHD, split into two subcategories: symptoms at 10-11 years, and symptoms at 12-13 years. Those in the former group were twice as likely -for each standard deviation increase in symptoms - as those without such symptoms to report suicide attempts persisting into adulthood versus never attempted. But they were no more likely to report adolescence-limited attempts versus never-attempted, or attempts persisting into adulthood versus adolescence-limited. Furthermore, there were no significant associations between ADHD symptoms at 12-13 years and any of the three foregoing categories.

The authors acknowledged, "despite the large sample size, the number of individuals who attempted suicide was low, limiting the statistical power ..."

Hyperthyroidism, an overactive thyroid gland, occurs in about one in five hundred women. It has been tied to adverse effects in both mother and fetus, including pre-eclampsia (a condition in pregnancy characterized by high blood pressure, sometimes with fluid retention and excessive protein in the urine, which can indicate kidney damage), preterm delivery, heart failure, and in uteri retardation of growth.

In hypothyroidism, on the other hand, thyroid activity is abnormally low, which retards growth and mental development. It is particularly common in regions with widespread iodine deficiency. Depending on the region, it affects one in three hundred to one in thirty women. Maternal hypothyroidism is associated with an increased risk of pre-eclampsia, premature separation of the placenta from the wall of the uterus, miscarriage, in uteri growth retardation, and fetal death.

The fetus relies on maternal thyroid hormones until its own thyroid function initiates halfway through pregnancy. As we have just seen, this direct link in the early stages of pregnancy has serious consequences described above. Does it also affect the risk of developing ADHD in offspring?

A team of researchers based in Hong Kong reformed a comprehensive search of the peer-reviewed medical literature on this subject. It then conducted two meta-analyses, one examining maternal hyperthyroidism during pregnancy, the other on maternal hypothyroidism.

The meta-analysis for maternal hyperthyroidism during pregnancy combined two nationwide cohort studies with a total of over 3.1 million persons, using the Danish and Norwegian medical registries. It found a slight but significant association with ADHD in offspring.

The meta-analysis for maternal hypothyroidism during pregnancy included the same two nationwide cohort studies, plus an Israeli nationwide cohort study (along with a tiny U.S. cohort study), with a total of over 3.4 million persons. It likewise found a slight but significant association with ADHD in offspring.

Though the component studies did some assessment of confounders, the authors of the meta-analyses noted, "By including a more comprehensive range of confounding factors and biologically relevant covariate (e.g. thyroxine treatment), future studies are warranted to re-visit the association between maternal thyroid dysfunction and various health outcomes in offspring."

Although there are numerous kinds of perfluoroalkyl substances (PFAS), the primary ones used in the manufacture of fluoropolymers are perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Because of their strong water-repelling properties, fluoropolymers are used in stain repellents, polishes, paints, and other coatings, as well as in water-resistant outdoor clothing. They are long-lasting and therefore both pervasive in the home and environment and subject to accumulation in our bodies, especially in urbanized and industrialized areas. These substances can be passed from mother to child both through the placenta and through breastfeeding.

With support from the European Union, a large international team of European and North American researchers set out to investigate possible associations between early-life exposure to PFOS and PFOA and subsequent ADHD. They performed a meta-analysis on nine European population studies encompassing 4,826 mother-child pairs.

Participants were restricted to live-born single births with data on concentrations of PFOS and/or PFOA, and available information on ADHD diagnosis or symptoms.

Because a) some studies looked at maternal serum/plasma, others at maternal breast milk; b) timing of sample collection varied (first trimester, delivery); and c) children's levels during the first two years of life were unavailable (ethical constraints limit drawing blood samples from infants), the team used a validated pharmacokinetic model of pregnancy and lactation to estimate pre-and postnatal concentrations of PFASs in offspring.

The team adjusted for seven potential confounders: maternal pre-pregnancy body mass index, maternal age at delivery, maternal education, maternal smoking, number of previous children, duration of breastfeeding, and child sex.

With these adjustments, no association was found between estimated exposures to either PFOS or PFOA at birth, at three months, and at two years and subsequent diagnosis or symptoms of ADHD. While the raw data showed slightly higher odds for girls than for boys to develop ADHD with identical exposures, the differences were statistically non-significant.

There's a widespread, but so far unsupported, popular belief that sugar consumption, and sugar-sweetened beverages, in particular, trigger symptoms, especially hyperactivity, in youth.

Given the steep rise of sugar consumption by youth, what evidence is there of a link to ADHD?  

An Iranian team of researchers carried out a comprehensive search of the peer-reviewed literature on this subject. It identified seven studies - two cross-sectional, two case-control, and three prospective " with a combined total of over 25,000 participants that were amenable to meta-analysis. The studies spanned the globe, including the United States, Brazil, Taiwan, the U. K., Spain, and Norway.

Using a fixed-effects model, they found a tiny 7.5% increase in ADHD associated with sugar consumption. With a random-effects model, that rose to a 22% increase. But correcting for publication bias with a trim-and-fill adjustment removed any evidence of an association (p = 0.8).

Even without adjusting for publication bias, subgroup analysis found no evidence of an association with sugar consumption per se.

On the other hand, two studies that looked exclusively at sugar-sweetened beverages reported an 80% increase in the odds of ADHD. There was no way to evaluate publication bias for just two studies. Furthermore, two studies are insufficient for a proper meta-analysis.

There are two conclusions to be drawn from this meta-analysis: 1) It reinforces previous findings of no significant association between sugar consumption and ADHD; 2) It suggests it would be worth conducting more studies, specifically focusing on sugar-sweetened beverages.

Parkinson's disease is a chronic, progressive neurological disease, characterized by the drastic reduction of dopamine transporters and the dopaminergic neurons upon which they are expressed. The resulting symptoms include bradykinesia (slowness of initiation of voluntary movements), tremors, rigidity, and postural instability.

Taiwan's National Health Service covers about 99 percent of its 24 million inhabitants, and maintains complete records in its National Health Insurance Research Database. The Longitudinal Health Insurance Database2000 (LHID 2000) is a nationally representative subset of the latter.

Using the LHID 2000, a Taiwanese research team identified10,726 patients with Parkinson's disease. It paired them with an identical number of randomly selected non-Parkinson's controls, matched by age, gender, and index date (first date of diagnosis of Parkinson's disease).

The team then looked retroactively through the database to determine which of the 21,452 individuals had previously been diagnosed with ADHD. Fourteen of the 10,726 Parkinson's patients had been diagnosed with ADHD, versus five of the 10,726 in the control group.

Parkinson's patients were thus 2.8 times as likely to have had a previous diagnosis of ADHD as the controls. When adjusted for age, gender, and Carlson Comorbidity Index scores, they were 3.6 times as likely to have had a previous ADHD diagnosis.

The authors cautioned that this association between prior ADHD diagnosis and subsequent Parkinson's diagnosis is not causal.

Only one in 766 of Parkinson's patients (a seventh of one percent) had previously been diagnosed with ADHD. So even if there were any causal relationship, it would be extremely weak.

The specific type of gaming disorder (GD) that is the focus of this review is "disordered video-gaming," or more precisely the addictive potential of interactive video games played on mobile phones, gaming consoles, individual computers, and over networks. Certain characteristics of such games, including structured rewards and multi-modal sensory stimulation, contribute to that addictive potential. Networked games also allow for direct social engagement through role playing and cooperation with others. They also lead to further opportunities for participation in a wider community of players on forums outside gameplay, such as discussion platforms, video play-through analyses, or live-streaming.

The authors performed a systematic search of the peer-review literature, and identified 29 studies exploring the relationship between Addend GD.

All studies found a positive association between ADHD and GD. Of studies reporting effect sizes, seven reported small effect sizes, three reported medium ones, and three reported large ones. There was a similarly wide variety of reported effect sizes among studies that reported correlations between ADHD scales and GD scales. These ranged from r = .12 (small) to r = .45(large).

Three studies examined longitudinal outcomes. One reported that lower ADHD scores at baseline predicted positive long-term recovery. Another noted that GD was more likely to develop into significant psychiatric symptoms and poorer educational outcomes two years later. The third study found that higher ADHD and GD scores were associated with higher incidences of delinquent or aggressive behaviors and externalizing problems, as compared to a sample with ADHD but not GD. All three studies reported that ADHD was a risk factor for the development of problematic gaming behavior. There was no clear indication of the reverse relationship - GD predicting ADHD.

The authors concluded, "This review found a consistent positive association between ADHD and GD, particularly for the inattention subscale. The strength of the association between ADHD and GD was variable. On symptom severity ratings, there was a positive relationship between scores measuring GD and ADHD pathology in some studies. Fewer studies in this review showed hyperactivity was commonly associated with GD. It is well known that hyperactivity in ADHD tends to improve significantly with age. It is possible that the natural progression of the disorder resulted in lower rates of hyperactivity. Such a hypothesis is strengthened by findings of a stronger association with hyperactivity among children aged between 4 and 8."

Ideas for policy interventions to address disordered video gaming include:

·        Parental controls on games.
·        Warning messages similar to those on cigarette packaging.
·        Organizing help services for gamers.

The authors called for further study on:

·        Effectiveness of intervention strategies.
·        The contribution of GD to the dysfunction associated with ADHD.
·        The relationship between the content of play (e.g., violence) and motivation to play (e.g., escapism) and ADHD symptoms.
role-playin·        The role of depression, anxiety, and another comorbidity in mediating the relationship between ADHD and GD

"Clinicians should beware that ADHD is common in GD," the authors emphasized, "and we, therefore, recommend that ADHD is screened for when evaluating GD as part of routine practice. This would ensure interventions aimed at ADHD can be successfully combined with GD treatment, potentially improving patient outcomes."

Threatened spontaneous abortion is defined as vaginal bleeding without cervix dilation within 20 weeks of the onset of pregnancy.

Risk factors include advanced age, obesity, lifestyle (e.g., caffeine intake, lack of physical exercise, stress, cigarette smoking, and alcohol intake), socioeconomic variables, and low serum progesterone. Progesterone is a female hormone that plays a key role in the implantation of the fertilized egg, formation of the placenta, and sustaining a pregnancy.

Threatened spontaneous abortion affects roughly a fifth of pregnancies in the first trimester (first three months). Up to 11 weeks into pregnancy, it seldom leads to spontaneous abortion, but after 11 weeks the likelihood shoots up to as high as half of the affected pregnancies.

Denmark has universal single-payer health insurance. A team of researchers at Aarhus University used their country's comprehensive administrative and healthcare registries to explore any possible association between threatened spontaneous abortion and subsequent ADHD.

That enabled them to analyze a nationwide population of 1,864,221 singletons (as opposed to multiple births such as twins or triplets) live-born from 1979 to 2010. Of these children,59,134 (3.2%) experienced threatened spontaneous abortion within 20 weeks of gestation.

The team adjusted for a series of covariants that could confound outcomes: characteristics of mothers [age at childbirth, pre-pregnancy co-morbidities (somatic, neurologic, psychiatric), healthcare use, medication use, income, education, and employment]; fathers (age on the date of the child's birth, psychiatric co-morbidities a history of epilepsy, cerebral palsy, and ADHD); and children (birth year, birth order).

With these adjustments, they found that children who had experienced threatened spontaneous abortion were a fifth (21%) more likely to have ADHD. But it's exceedingly difficult to account for all confounding variables.

Because of the enormous size of the sample, however, the team was also able to compare 15,875 individuals who experienced threatened spontaneous abortions with an equal number of their paired full siblings who did not, to examine the effect of residual confounding variables. This time, they found no significant differences in the likelihood of ADHD between full siblings.

The authors observed that "controlling for family-shared factors, including genetic makeup and other factors remaining constant between pregnancies and in children's early environments, removed family-shared confounding." They concluded, "After removal, by the sibling design, of time-invariant family-shared confounding, there was no evidence of an increased risk of epilepsy or ADHD among TAB [Threatened Abortion]-affected children."

What are the links between ADHD and physical ailments in adults? And, where such links exist, how can we tease out where they are due to genetics, shared environment, or unshared environmental influences?

An international research team used the Swedish population and health registers to explore these links in an entire national population. They were able to do this because Sweden has a single-payer national health insurance system, cross-referenced with the population and other national registries through personal identification numbers.

This study identified full-sibling and maternal half-sibling pairs born from 1932 through 1995, through the Population and Multi-Generation Registers. This yielded a total of 4,789,799 individuals - consisting of 3,819,207 full-sibling pairs and 469,244 maternal half-sibling pairs, and 1,841,303family clusters (siblings, parents, cousins, spouses). Roughly half were men, the other half women.

After adjusting for sex and birth year, those with ADHD were at significantly higher risk of a wide range of physical ailments, when compared with individuals without ADHD:

·        Over four times as likely to have sleep disorders or develop alcohol-related liver disease;
·        Roughly three times as likely to develop the chronic obstructive pulmonary disease, epilepsy, and fatty liver disease;

·        Over two and a half times more likely to become obese.

Overall, ADHD was significantly associated with 34 of the 35 physical diseases studied, rheumatoid arthritis being the only exception.

Comparing men with women, women with ADHD were at significantly greater risk of atrial fibrillation, urolithiasis, sleep disorders, and asthma than men with ADHD. Conversely, men with ADHD faced a greater risk of thyroid disorder than women with ADHD.

Between-sibling analyses showed that full siblings of individuals with ADHD were at significantly increased risk for 27 of the 35 physical ailments, suggesting that shared familial factors contributed to the co-occurrence of the conditions. This remained true even after adjusting for the occurrence of ADHD in full siblings.

These associations were generally reduced in maternal half-siblings of individuals with ADHD. The associations between full-siblings were significantly stronger than between maternal half-siblings for type 1 diabetes, obesity, kidney infections, back or spine pain, migraine, sleep disorders, asthma, and chronic obstructive pulmonary disease.

Keep in mind that full-siblings on average share half of their genes, whereas maternal half-siblings share only a quarter of their genes. Maternal (as opposed to paternal) half-siblings were chosen as a basis for comparison because they are typically brought up together in the same family setting, and thus are similar to full-siblings in having a shared family environment. Reduced risk in maternal half-siblings would therefore signal a genetic component to the risk.

Given that ADHD is itself a nervous system disorder, it is unsurprising that it correlated most strongly with other nervous system disorders, with a medium effect size (r=.23). Genetic factors explained over a quarter of the correlation, shared environmental factors over a seventh, and non-shared environmental factors the other three-fifths. The latter could point to environmental risk factors that influence both ADHD and nervous system diseases.

Small-to-medium correlations were found with metabolic, respiratory, and musculoskeletal disease groups, with genetic factors explaining roughly two-thirds of the correlation, and non-shared environmental factors most of the rest.

The authors concluded that "adults with ADHD are at increased risk of a range of physical conditions, across circulatory, metabolic, gastrointestinal, genitourinary, musculoskeletal, nervous system, respiratory, and skin diseases. Most physical conditions showed familial associations with ADHD (mainly from genetic factors). Our findings highlight the need for rigorous medical assessment and care in adult patients with ADHD, and suggest long-term consequences of age-related diseases."