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Polycystic ovary syndrome (PCOS) affects somewhere between 6 and 20% of women of reproductive age. Typical effects include:
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·  failure to ovulate;

·      high levels of male hormones (androgens), which can lead to acne, seborrhea, hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation;

·       metabolic disruption, including obesity and insulin resistance.

In pregnancy, PCOS is also known to increase the chances of birth complications.

Previous studies have suggested a link between maternal PCOS and ADHD.

A team of Arabian (Saudi and United Arab Emirates) researchers conducted a systematic review of the peer-reviewed medical literature and were able to identify four studies with a total of 1,354,182 participants that could be combined into a meta-analysis.

The meta-analysis found that children born to mothers with PCOS were 43% more likely to develop ADHD. The 95% confidence interval stretched from 35% to 51%, indicating a highly reliable finding.

Moreover, there was between-study variation: They all produced essentially identical results. There was also no sign of publication bias.

"However,"the authors noted, "the reported results do not necessarily provide definitive findings of a causal inference due to the randomized study design. All the included studies were observational in design." With this caution, they could only conclude that "the results of this meta-analysis showed that there might be a link between maternal PCOS and the risk of developing ASD and ADHD in the offspring."

Previous meta-analyses have found an association between cesarean delivery (CD) and subsequent ADHD in children delivered in that manner. Some have theorized that by bypassing the birth canal, children delivered via CD may acquire their first microbiota from the hospital environment rather than from their mothers, which could disturb the normal development of the nervous system, including the brain.

Nevertheless, earlier studies have not fully explored the role of confounding factors.

A team of Swedish researchers availed themselves of the country's all-encompassing system of national population and health care registers to examine a cohort of over a 1.1 million single births from 1990 through 2003 and followed up through 2013.

They distinguished between planned CD and intrapartum (i.e., during the act of birth) CD. The latter is performed in response to complications with childbirth. This distinction could matter both because of different levels of exposure to the maternal gut microbiota, and because "intrapartum CD is often the result of complications during pregnancy (e.g., preeclampsia) or delivery (e.g., fetal distress), which could affect brain development."

Of 1,179,341 individuals, 1,048,838 were delivered vaginally, 59,514 were delivered by planned CD, and 70,989 were delivered by intrapartum CD.

After adjusting for the child's year of birth, gestational age, age of mother and father at birth, parity, mother's highest education level at birth, maternal smoking during pregnancy, maternal and paternal history of psychiatric disorders, maternal hypertension, maternal diabetes, maternal infections during pregnancy, fetal MAL presentation, large for gestational age, polyhydramnios, oligohydramnios, preeclampsia, and pelvic disproportion, children born by planned CD were 17% more likely to have ADHD.

After adjusting for all previously listed variables plus placenta disorders, dystocia failed induction, and fetal distress, children born by intrapartum CD were 10% more likely to have ADHD.

So far, the analysis confirmed results from previous meta-analyses.

But by exploring such a large cohort, it also became possible to compare ADHD prevalence, not only among unrelated individuals, but also among siblings and cousins, and thereby assess the role of confounders arising from genetics or shared environment.

Whether between full siblings or full maternal cousins, the associations between both types of CD and subsequent ADHD became weak and statistically non-significant.

The authors concluded, "The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding."

Alzheimer's disease is characterized by an aging-related progressive deterioration in cognition and ability for independent living. It is the most common form of dementia. Few studies, with limited sample sizes, have probed the relationship between ADHD and dementia, with conflicting results.

A Swedish study team used the country's universal system of population and health registers' linked through unique personal identification numbers - to examine patterns among the more than 2.1 million Swedes born between 1980 and 2001.

Each of these individuals was then linked to their biological relatives, parents, grandparents, uncles, and aunts through the Medical Birth Register and Multi-generation Register.

This generated three cohorts of relatives representing different levels of genetic relatedness: parents sharing half of their genes; grandparents sharing a quarter of their genes; and uncles and aunts who also share a quarter of their genes with index persons. After linking index persons to their biological relatives, the study cohorts contained more than 2.2 million parents, over 2.5 million grandparents, and almost a million uncles/aunts.

By the end of follow-up, 3,042 (0.13%) parents, 171,732 (6.82%) grandparents, and 1,369 (0.15%) uncles/aunts had a diagnosis of Alzheimer's. The numbers for any dementia were 3,792 (0.17%) for parents, 197,843 (7.86%) for grandparents, and 1,697 (0.18%) for uncles/aunts.

Parents of persons with ADHD were 34% more likely to have any dementia, and 55% more likely to have Alzheimer's. Among grandparents of persons with ADHD, the association dropped to 10-11% more likely for any kind of dementia. Among aunts and uncles, it dropped to a 14% greater likelihood of Alzheimer's(similar to grandparents) and a 4% greater chance of any dementia. In this case, however, the results were not statistically significant, probably due in part to the much smaller sample size

Both with parents and grandparents of persons with ADHD, the risk of early onset of any kind of dementia was well over twice as high as the risk of late-onset.

"We found that ADHD aggregated with AD [Alzheimer's disease] and any dementia within families, and the strength of association attenuated with decreasing degree of genetic relatedness," the authors concluded, and called for further studies to identify genetic variants and family-wide environmental risk factors contributing to both conditions. If verified by such studies, that would indicate a need for "investigation of early-life psychiatric prevention on the development of neurodegenerative diseases in older age."

Persons with ADHD have known to have high rates of psychiatric comorbidities. There is also growing evidence of somatic (non-psychiatric) comorbid disorders among youths with ADHD, such as metabolic syndrome (which can lead to type 2 diabetes) and chronic inflammation (such as asthma and allergic rhinitis). Much less is known, however, about comorbid conditions in adults with ADHD.

An international team of researchers looked for indicators of comorbid conditions in a nationwide cohort study using Swedish national registers. The target population was Swedish residents between the ages of 18 and 64 in 2013 and more specifically those who had been prescribed ADHD medication. They identified over 41,000 individuals who met these criteria, including over twenty thousand young adults aged 18-29 years, over sixteen thousand middle-aged adults aged 30-49 years, and over four thousand older adults aged 50-64. The remainder of the overall cohort were used as controls.

Young adults receiving ADHD medications were four times as likely to also be receiving somatic medications, and older adults were seven times as likely. The highest rate of co-medication -roughly five times more frequent than among controls - was for respiratory system medications. The second most common was for alimentary tract and metabolic system medications, with odds over four times higher than for controls. Cardiovascular system medications were the next most common, with odds among young adults receiving ADHD medications over four times those of controls, though reducing with age to being twice as common in older adults with ADHD. Patterns were similar among men and women.

Adults receiving ADHD medications were far more likely to also be receiving other psychotropic medications. Middle-aged adults were 21 times as likely to be dispensed such medications as controls, older adults eighteen times more likely, and younger adults fifteen times more likely.

For young adults prescribed ADHD medications, the most prevalent co-prescriptions were for addictive disorders, which were dispensed at over 26 times the rate for controls. For middle-aged and older adults, on the other hand, the most prevalent co-prescriptions were for antipsychotics, which were likewise dispensed at over 26 times the rate for controls. Results remained consistent for individuals who had an ADHD diagnosis in addition to an ADHD prescription.

In addition, individuals receiving ADHD medications were also on average taking more types of prescriptions, rising from 2.5 classes of medications at age 18 to five classes at age 64. For controls, the equivalent numbers were 0.9 types of medications at age 18, rising to 2.7 at age 64.

Looking at specific somatic medications prescribed, those for respiratory conditions were ones typically prescribed for asthma and allergic reactions, reinforcing a previously known association. Insulin preparations also had high rates of co-prescription, again further confirming the known association with obesity and diabetes.

On the other hand, the most commonly dispensed alimentary tract and metabolic system medications included proton pump inhibitors, typically prescribed for gastric/duodenal ulcers and gastroesophageal reflux disease. Sodium fluoride, prescribed to prevent dental caries, was also prominent. Neither of these is an established association and warrants further exploration.

Turning to psychotropic medications, the most frequent prescriptions were with drugs used to treat addictive disorders and with antipsychotics. Rates of opioid co-prescription were also notably high, a source of concern given the higher proclivity of persons with ADHD to substance use disorders.

A Chinese research team recently conducted a systematic search of the peer-reviewed medical journal literature for studies exploring the association between childhood antibiotic exposure and subsequent diagnosis of ADHD in youths 18 years and younger.

A meta-analysis of six studies with a combined total of over 1.5 million participants found that children exposed to antibiotics were 18% more likely to later be diagnosed with ADHD.

There was absolutely no indication of publication bias. Between-study heterogeneity, on the other hand, was extremely high.

With such large cohorts, one can often tease out whether an association is causal, or due to genetic and familial confounding, by looking at matched close relatives.

Three of the studies, with a combined total of well over half a million participants, also compared matched siblings.

Significantly, the meta-analysis among matched siblings found no association whatsoever between childhood exposure to antibiotics and subsequent ADHD. Between-study heterogeneity was virtually nonexistent.

The team concluded, "Our meta-analysis indicated that early-life antibiotic exposure was associated with a subsequent increased risk of ASD or ADHD. However, such association was not found in the sibling-matched analysis, indicating that genetic and familial confounding factors may largely explain the observed association."

A team of Taiwanese researchers availed themselves of the country's National Health Insurance Research Database (NHIRD) to explore the links between exposure to general anesthesia and ADHD. Taiwan has a single-payer health insurance system that encompasses 99% of its more than 23 million residents. NHIRD is a database of one million persons randomly selected from those insurance records.

The study sample consisted of 43,377 children under three years old who were admitted to hospitals between 1997 and 2008, with or without exposure to general anesthesia.

Next, individuals from both groups were matched by age, gender, and admission to the hospital within a week of each other. Two controls not exposed to general anesthesia were matched to every case that was exposed. The resulting cohort of cases with exposure to general anesthesia totaled 2,261 matched to 4,522 controls without such exposure.

Of the inpatients exposed to anesthesia, 67 (2.96%) were subsequently diagnosed with ADHD, whereas among those not exposed, 139 (3.07%) were subsequently found to have ADHD. After adjusting for allergic diseases and age, those exposed to anesthesia were 6% less likely to be diagnosed with ADHD, but the result lacked any statistical significance.

The authors concluded, "There was no significant difference in the overall incidence of ADHD, autism and intellectual disability between the GA-exposed group and the comparison cohort."

China is the outstanding economic growth story of the early twenty-first century. According to the World Bank, China has "experienced the fastest sustained expansion by a major economy in history, and has lifted more than 800 million people out of poverty."

That expansion has been accompanied by major investments in medical research, and medical treatment capability, especially in the major urban centers that have spearheaded the boom. Life expectancy has risen from 71 in 2000 to 77 in 2019, nearing the U.S. level of 79.

Yet when it comes to pharmaceutical treatment of ADHD, China is an outlier, as revealed by a new study exploring the data in the two main medical insurance programs for its urban population.

The Urban Employee Basic Medical Insurance (UEBMI) covers both employers and employees in public and private workplaces, while the Urban Residents Basic Medical Insurance (BMI) covers the unemployed. As of 2014, these programs cover over 97% of urban residents. The China Health Insurance Research Association (CHIRA) database is a random sampling database from the UEBMI and UBMI databases.

The study population consisted of residents of the 63 cities in the CHIRA database from 2013 through 2017. Prescription prevalence was calculated by dividing the total number of patients prescribed ADHD medications in the CH IRA database by the urban population of the included cities, which was two hundred million as of 2017.

Other studies have found the prevalence of ADHD among Chinese children and adolescents to be about 6.5%, comparable to North American and European countries. Yet, the prescription prevalence of ADHD medications was 0.036% among those aged 0-14 years in 2017 in China. In other words, only about one in every two hundred youths with ADHD were being prescribed pharmaceutical treatments.

For further context, among other economically prosperous countries in Asia, Australia, North America, and Europe, the lowest prescription prevalence of ADHD medications is 0.27% in France, which is still over seven times higher than the Chinese level.

Among Chinese urban dwellers from 15 through 64 years of age, ADHD prescription prevalence in 2017 dropped by a further order of magnitude (over tenfold) to 0.003%, and among those 65 and older, to a scant 0.001%.

The Chinese study team suggested several likely contributing factors:

• Lack of training in ADHD treatment among clinical practitioners;
• Government fears of addiction have led to strict control of stimulant medications;
• Discontinuation of methylphenidate production by Chinese pharmaceutical enterprises in 2009 meant having to purchase more expensive imported ADHD medications;
• Widespread parental belief that ADHD is just "bad behavior," not a disease requiring medication;
• Parental reliance on alternative treatments, such as Traditional Chinese Medicine (TCM)