Precocious puberty (PP) is defined as the onset of secondary sex characteristics before age 8 in girls or age 9 in boys.  

Because it accelerates skeletal maturation by prematurely shutting down the cartilage growth plate at the tip of long bones, it tends to lead to shorter height in adulthood. It is also known to place an additional psychological burden on children, especially girls. Girls are four to 38 times more likely to develop PP than boys. 

Taiwan has a single-payer national health insurance system, called National Health Insurance, that encompasses 99.6% of the island’s population. The Ministry of Health and Welfare uses it to maintain the National Health Insurance Research Database (NHIRD), enabling researchers to conduct nationwide population studies. 

Using this database, a Taiwanese study team investigated the relationship between ADHD and precocious puberty among children and adolescents (under 18). And because methylphenidate (MPH) is the only psychostimulant approved for the treatment of ADHD in Taiwan, the team also explored the effect of MPH on this relationship. 

Most diagnoses of ADHD in the NHIRD are made by board-certified psychiatrists, enhancing diagnostic validity. 

Of the more than 3.3 million persons born in Taiwan between 1997 and 2001, 186,681 were diagnosed with ADHD. Of these, 122,302 were prescribed MPH. 

After adjusting for sex, low-income households, and neuropsychiatric comorbidities, children diagnosed with ADHD were twice as likely to be diagnosed with PP. This held equally true for boys and girls. 

However, children diagnosed with ADHD and prescribed MPH were more than a third less likely to subsequently be diagnosed with PP than those diagnosed with ADHD but not prescribed MPH.  

For girls with ADHD, who without an MPH prescription were nine times more likely than boys with ADHD to be diagnosed with PP, an MPH prescription reduced that ratio to five times more likely than boys with ADHD and prescribed MPH. 

That suggests a strong protective effect of MPH.  

The team concluded, “Our study found that children with ADHD were at a greater risk of PP, and girls with ADHD were a particularly vulnerable group. … MPH appeared to be protective against PP in patients with ADHD, especially in girls. However, these preliminary results need further validation.” 

‍

Maternal infections and inflammatory responses during pregnancy have been proposed as risk factors for neurodevelopmental disorders such as ADHD. 

Taiwan has a single-payer health insurance system that covers virtually the entirety of its population. Its Ministry of Health and Welfare maintains the National Health Insurance Research Database (NHIRD), with detailed information on outpatient services, hospitalizations, and medical treatment for nearly 99% of all residents. 

A Taiwanese study team used NHIRD to examine to examine the relationship between maternal hospitalization for infection, and early childhood infection, and subsequent ADHD in offspring. The study cohort originated with all 3,260,879 individuals born between 2001 and 2018. 

The team excluded births from foreign mothers, still births, births with congenital defects, low birth weights, abnormally late births, twins, triplets, and other multiple births, culminating in a final population cohort of 2,885,662 live-born single infants across 1,893,171 families, and 1,864,660 individuals with full siblings from 872,169 families comprising the full sibling cohort. 

Study participants were followed until diagnosis of a neurodevelopmental disorder, their death, or the end of 2021. 

After adjusting for sex, birth year, paternal and maternal ages, birthweight, birth season, parity, delivery method, 1 minute APGAR score (evaluating baby’s appearance, pulse, grimace, activity and respiration at birth), gestational age, pregnancy and delivery complications, parental history of neurodevelopmental disorders, maternal asthma and diabetes, urbanization level of the residential area, and family’s insurance amount, offspring of mothers hospitalized for infections had 14% greater odds of being subsequently diagnosed with ADHD. 

However, in the full sibling cohort of over 1.8 million, this association vanished. That held true for each of the three trimesters of pregnancy. It also held true for bacterial infections. Surprisingly, offspring of mothers hospitalized for viral infections were 24% less likely to be diagnosed with ADHD than their siblings not exposed to maternal viral infection. Because of that, they also had a 6% lower risk overall. 

After the same adjustments, early childhood infection was associated with 16% greater odds of being diagnosed with ADHD. 

Nevertheless, in the full sibling cohort of over 1.8 million, this association again vanished. That held true overall, as well as separately for childhood infections in months 1-6 and months 7-12. The association vanished altogether both for bacterial infections as well as for viral infections. 

The authors concluded, “the results of this nationwide birth cohort study with population and sibling analyses suggest that the association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors.” 

‍

Background: 

Noting that “the results of previous investigations into the therapeutic benefits of probiotics in the treatment of ADHD symptoms remain inconsistent,” a Taiwanese study team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis. 

The Study:

The team identified seven randomized controlled trials (RCTs) that met criteria for inclusion: focusing on children and adolescents under 18, with ADHD diagnoses, comparing probiotic interventions with placebo, and using standardized behavioral rating scales to assess ADHD symptoms. 

Meta-analysis of these seven RCTs with a combined total of 342 participants found no significant improvement in ADHD symptoms. In fact, six of the seven RCTs clustered tightly around zero effect, while the seventh – a small sample (38) outlier – reported a very large effect size improvement.  

Meta-analysis of the three RCTs with a combined 154 individuals that used probiotics with single strains of microorganisms showed absolutely no improvement in ADHD symptoms with no between-study variation (heterogeneity). 

Meta-analysis of the four RCTs with a total of 188 participants that used multiple strains pointed to a medium – but statistically nonsignificant – effect size improvement, with high heterogeneity. Removing the previously mentioned outlier RCT collapsed the effect size to zero. 

Two of the RCTs (with 72 total individuals), including the outlier, offered probiotics in conjunction with methylphenidate treatment. Meta-analysis of the other five RCTs with 270 persons that were structured around pure supplementation yielded absolutely no improvement in ADHD symptoms with no heterogeneity. 

Meta-analyses of the four RCTs with a combined total of 238 participants that examined ADHD subtypes reported no effect on either inattention symptoms or hyperactivity/impulsivity symptoms. 

Trivially, given the lack of efficacy, probiotic regimens were tolerated as well as placebo. 

The Take-Away: 

Ultimately, this meta-analysis found no evidence that probiotics improve ADHD symptoms in children and adolescents. Across seven randomized controlled trials, results consistently showed no significant benefit compared to a placebo. While probiotics were well-tolerated, they did not meaningfully impact inattention, hyperactivity, or impulsivity. These findings suggest that probiotics, whether single or multi-strain, are not an effective treatment for ADHD.

‍

The Background:

Caffeine and its primary breakdown compounds – paraxanthine, theophylline, and theobromine (also the primary alkaloid in chocolate) – readily cross the placenta and tend to linger due to the underdevelopment of fetal caffeine metabolizing enzymes.

Could accumulating caffeine metabolites harm the developing fetal brain? Studies to date have come to contradictory conclusions, some finding an association, others finding none.

Norway has a national single-payer health insurance system with a national health registry comprehensively tracking virtually all residents.

The Methods:

An international study team used Norways’s registry, and its Mother, Father, and Child Cohort Study (MoBa) to explore the relationship between maternal and paternal coffee consumption and offspring neurodevelopmental difficulties (ND), including symptoms of ADHD as determined from validated rating scales, using 58,964 mother-child pairs and 22,576 father-child pairs, covering the decade 1999-2008.

Unadjusted results indicated a strong association between maternal coffee consumption before and during pregnancy with offspring ADHD, but none with paternal coffee consumption. Superficially, that might seem like compelling evidence.

Yet after adjusting for education, income, smoking, and alcohol, “previously significant effects attenuated towards zero and some associations switched from being positive to negative.”

Then, after further adjusting for genetic confounding, ADHD symptoms at 1.5 years, 3 years, 5 years (on both of two different rating scales), and 8 years (including separate measures of inattention and hyperactivity symptoms) all became indistinguishable between offspring from mothers consuming coffee during pregnancy and offspring of mothers abstaining from coffee during pregnancy. 

Conclusion:

The team concluded, “This study applied several conventional and genetic epidemiological approaches to investigate the potential relationship between maternal coffee consumption during pregnancy and offspring NDs [neurodevelopmental difficulties]. When considering the results of the conventional and genetic epidemiological analyses, as well as the broader literature, we conclude that there is little evidence that maternal coffee consumption during pregnancy is strongly causally related to offspring NDs.”

More specifically, the team found no evidence of any causal relationship with offspring ADHD. 

‍

Congenital cleft lip and palate (CCLP) are birth defects associated with genetic and environmental factors. The latter include heavy maternal consumption of alcohol and fetal exposure to retinoid drugs derived from vitamin A. 

Methods:

Taiwan has an island-wide single-payer health insurance system that reaches over 99% of the population. To explore the relationship between CCLP and various psychiatric disorders including ADHD, a Taiwanese study team used the island’s National Health Insurance Research Database to identify all 1,158 children and adolescents with CCLP during a ten-year period. They matched them ten-to-one with 11,580 age and sex-paired controls without CCLP. 

Summary of Results:

Further adjusting for demographic data (income, residence) and family history of major psychiatric disorders, children and adolescents with CCLP were more than seven times more likely to be diagnosed with ADHD during the follow-up period than controls. Patients with both cleft palate and cleft lip were more than nine times more likely to be subsequently diagnosed with ADHD than controls. 

Patients with CCLP were also six times more likely to be diagnosed with autism spectrum disorder and more than seven times as likely to be diagnosed with schizophrenia as non-CCLP controls. They were also more likely to be diagnosed with bipolar disorder or major depressive disorder, but these results did not reach statistical significance. 

Conclusion:

This study highlights a significant association between congenital cleft lip and palate (CCLP) and an increased risk of developing ADHD, with CCLP patients being more than seven times as likely to be diagnosed with the disorder. Additionally, CCLP was linked to a higher prevalence of other psychiatric conditions, including autism spectrum disorder and schizophrenia. These findings underscore the importance of monitoring mental health in individuals with CCLP and call for further research into the risk factors connecting these birth defects with psychiatric disorders.

‍

Bipolar disorder is a severe mental illness that afflicts over one in fifty persons worldwide. About a quarter of those with bipolar disorder also has alcohol use disorder (AUD). This in turn complicates the treatment of their bipolar disorder. It exacerbates their symptoms, makes them more likely to be suicidal, and increases the risk of hospitalization.

More than one in five persons with bipolar disorder also have ADHD, which is likewise known to be correlated with AUD. To what extent does ADHD contribute to AUD in persons with comorbid bipolar disorder?

A European study team recently conducted a systematic search of the peer-reviewed medical literature to address that question. The team identified eleven studies with a combined total of 2,734 participants that could be aggregated to perform a meta-analysis.

They found that persons with comorbid ADHD and bipolar disorder were two and a half times more likely to be diagnosed with alcohol use disorder than persons with bipolar disorder but no ADHD.

Between-study heterogeneity was negligible, and there was no sign of publication bias.

The authors concluded, "At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship."

Oxytocin is a hormone released by the pituitary gland that stimulates the contraction of the uterus during labor. Synthetic oxytocin is widely administered during labor to supplement a birthing parent's supply and facilitate childbirth.

Previous studies have found an association between synthetic oxytocin and increased odds of ADHD in offspring.

A joint Danish and Finnish team used their countries' national registers to obtain countrywide cohorts encompassing over 577,000 Danes and over 945,000 Finns. Oxytocin had been administered in 31% of the Danish deliveries and 46% of the Finnish ones. Any children either diagnosed with ADHD or who received prescriptions for ADHD drugs were categorized as having ADHD.

As in previous studies, unadjusted results found a significant association with ADHD. Combining the two populations, children whose mothers had received oxytocin during labor were 16% more likely to later develop ADHD.

After adjusting for a series of confounders such as birth year, maternal age, education, marital status, parity, smoking in pregnancy, labor induction, gestational age, and intrauterine growth, the association dropped markedly, to an increased likelihood of barely 3%.

Looking at Denmark alone, the unadjusted risk was 9% greater, vanishing altogether after adjusting for confounders. In Finland, the unadjusted risk was 20% greater, declining to 4% after adjusting for confounders.

The authors noted that "Exposure to obstetric oxytocin is not a random process, and it is likely that other factors than the ones included here vary systematically between women treated vs not treated with oxytocin. ... Therefore, we find it most likely that the minor elevations in risk are due to uncontrolled and residual confounding, and thereby our results underscore the lack of a causal association between obstetric oxytocin exposure and ADHD."

After noting that the association between ADHD and obesity has been called into question because of small sample sizes, wide age ranges, self-reported assessments, and inadequate attention to potential confounders, an Israeli study team set out "to assess the association between board-certified psychiatrist diagnoses of ADHD and measured adolescent BMI [body mass index] in a nationally represented sample of over one million adolescents who were medically evaluated before mandatory military service."

The team distinguished between severe and mild ADHD. It also focused on a single age group.

All Israelis are subject to compulsory military service. In preparation for that service, military physicians perform a thorough medical evaluation. Trained paramedics recorded every conscript's height and weight.

The study cohort was divided into five BMI percentile groups according to the U.S. Centers for Disease Control and Prevention's BMI percentiles for 17-year-olds, and further divided by sex: <5th percentile (underweight), 5th-49th percentile (low-normal), 50th-84th percentile (high normal), 85th-94th percentile (overweight) and ≥95th (obese). Low-normal was used as the reference group.

Adjustments were made for sex, birth year, age at examination, height, country of birth (Israeli or other), socioeconomic status, and education level.

In the fully adjusted results, those with severe ADHD were 32% more likely to be overweight and 84% more likely to be obese than their typically developing peers. Limiting results to Israeli-born conscripts made a no difference.

Male adolescents with mild ADHD were 24% more likely to be overweight, and 42% more likely to be obese. Females with mild ADHD are 33% more likely to be overweight, and 42% more likely to be obese. Again, the country of birth made no difference.

The authors concluded, that both severe and mild ADHD was associated with an increased risk for obesity in adolescents at the age of 17 years. The increasing recognition of the persistence of ADHD into adulthood suggests that this dual morbidity may have a significant impact on the long-term health of individuals with ADHD, thus early preventive measures should be taken.

It is difficult enough for a typical child to manage type-1 diabetes. For a child that also has ADHD, with learning difficulties, attention and memory problems, and limitations in social communication, it can be all the more challenging to carry out the complex tasks necessary to maintain glycemic control (control of blood sugar levels) and avoid diabetic harm.

To explore the additional risk associated with ADHD among children with type-1 diabetes, an international research team used the Swedish national registers to conduct a nationwide population study. Sweden has a single-payer national health insurance system, and assigns unique personal identification numbers to all residents, making it easy to cross-reference through various population and health registers.

The team used the Swedish Diabetes Register to identify all individuals born in Sweden from 1973 onwards with childhood-onset type 1 diabetes diagnosed before age 18. They then restricted the cohort to those who had no diabetic complications at diagnosis and whose HbA1c values had been recorded within 5 years of diagnosis.

Also known as the glycated hemoglobin test, HbA1c is an indicator of the average blood sugar (glucose) level over the past three months. When glucose builds up in the blood, it binds to the hemoglobin in red blood cells. The HbA1ctest measures bound glucose. Since red blood cells live for about 3 months, the test shows the average blood glucose over that period.

The team also searched for records of diabetes-related kidney damage (nephropathy) and damage to the retina (retinopathy). Diabetic retinopathy is the leading cause of blindness among working-age adults.

The nationwide cohort consisted of 11,326 Swedish youths diagnosed with type-1 diabetes, of whom 415 (3.7%) were also diagnosed with ADHD.

Poor glycemic control, defined as mean HbA1c greater than 8.5%, was found in 38% of those with ADHD, twice the 19% found in those without neurodevelopmental disorders. After adjusting for confounders(sex, age at diabetes diagnosis, year of birth and year of diabetes diagnosis, another psychiatric morbidity, parental highest education level, parental psychiatric morbidity, smoking status, mean BMI [body mass index], and mean systolic and diastolic blood pressure), those with ADHD were 2.3 times as likely to have poor glycemic control.

Patients with ADHD were also almost twice as likely to suffer kidney damage, after adjusting for sex, age at diabetes diagnosis, year of birth, year of diabetes diagnosis, another psychiatric morbidity, parental highest education level, parental psychiatric morbidity, mean HbA1c levels, mean BMI, systolic and diastolic blood pressure, and smoking status.

After the same adjustments, patients with ADHD were found to be a third (33%) more likely to suffer retinal damage.

The team concluded, "childhood-onset type 1 diabetes patients with neurodevelopmental disorders, especially those with ADHD or intellectual disability, are more prone to poor glycemic control and a higher risk of chronic diabetic complications compared with those without neurodevelopmental disorders.

Further longitudinal studies with a more comprehensive evaluation of diabetes management and molecular data are needed to provide insight into potential mediators in the association between comorbid neurodevelopmental disorder and diabetes complications in type 1 diabetes."

Bilirubin is an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile. Elevated levels in blood serum can cause jaundice, a yellowing of the skin, or whites of the eyes.

More than one in twenty Swedish newborns are treated for neonatal jaundice, which is particularly common among preterm babies. It is usually benign.

A team of Swedish researchers used e Swedish Medical Birth Register, which contains information on all children born in the country, to identify all 814,420 single births without birth defects between 1992 and 2000, and followed them until 2009. They then identified instances of neonatal jaundice and of ADHD through linked nationwide medical registers.

The team also identified a sub-sample of full siblings (384,290 children from 181,354 families) in order to control for shared familial traits.

In the unadjusted results, children with any kind of neonatal jaundice were 38% more likely to be diagnosed with ADHD. After adjustment for known confounding variables, two-thirds of the association disappeared, with a residual increased risk of 13%.

There are, however, two types of neonatal jaundice: hemolytic and non-hemolytic. Hemolytic jaundice is typically caused by the mother's immune system mistaking the fetus' red blood cells as a threat, and responding by attacking with antibodies, rupturing and destroying the cells.

The study found no association between hemolytic jaundice and ADHD, either in the raw results or after adjusting for known confounders. Unsurprisingly, there was also no association in the sibling comparison.

That meant that all the association was concentrated among children born with non-hemolytic jaundice, who in the crude results were 43% more likely to subsequently develop ADHD. Adjusting for known confounders again reduced the association by two-thirds, to 14%. But among siblings, that association vanished altogether. Children born with non-hemolytic jaundice were no more likely than their non-jaundiced siblings to develop ADHD.

The authors concluded that "neonatal jaundice is not likely a causal risk factor for ADHD."

Denmark has a universal health insurance system that requires tracking all health care data in a system of national registries. That makes it possible to explore what's going on in an entire national population, rather than have to rely on sampling a small part of it, and hoping the sampling is reasonably representative.

A team of Danish researchers used the Civil Registration System to identify all single births through 1993 through 2014 and linked those records to corresponding records in the Psychiatric Central Research Register and National Patient Register for the years 2011through 2016. There were 1,397,850 youths in that cohort, of whom 12,844 were diagnosed with ADHD during the study period.

At five years of follow-up after diagnosis, almost three in ten youths with ADHD (29 percent) had registered evidence of sleep problems (including the use of melatonin, which is by prescription only in Denmark). For those with concomitant conduct disorder, almost half (45 percent) had registered evidence of sleep problems.

In the general population, on the other hand, the cumulative risk of sleep problems at five years of follow-up varied from one in a hundred for children followed from age 5 or age 10 to one in forty for those followed from age 15.

After adjusting for the confounding effects of three other neurodevelopmental disorders - autism spectrum disorder, oppositional defiant disorder/conduct disorder, and epilepsy­- youths with ADHD were still roughly 23 times more likely to have sleeping problems than were normally developing youths.

The authors cautioned, however, that the low rate of sleep problems in the general population "may indicate that sleeping problems without coexisting neurodevelopmental disorders are generally diagnosed or treated in primary health care (and hence not included in our study)."

A further limitation, they added, is that "we can not exclude the possibility of residual confounding. Thus, it remains unclear whether neurodevelopmental disorder contributes to the sleep problem or whether certain unmeasured characteristics of children with neurodevelopmental disorders may explain the apparent association with sleep problems."

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.

Youths with disabilities face varying degrees of social exclusion and mental, physical, and sexual violence.

A Danish researcher used the country's extensive national registers to explore reported sexual crimes against youths across the entire population. Of 679,683 youths born from 1984to 1994 and between the ages of seven and eighteen, 8,039 (1.2 percent) were victims of at least one reported sex crime.

The sexual offenses in question included rape, sexual assault, sexual exploitation, incest, and indecent exposure. Sexual assault encompassed both intercourse/penetration without consent or engaged in with a youth not old enough to consent (statutory rape).

The study examined numerous disabilities, including ADHD, which was the most common one. It also performed a regression analysis to tease out other covariants, such as parental violence, parental inpatient mental illness, parental suicidal behavior or alcohol abuse, parental long-term unemployment, family separation, and children in public care outside the family.

In the raw data, youths with ADHD were 3.7 times more likely to be a victim of sexual crimes than normally developing youths. That was roughly equal to the odds for youths with an autism spectrum disorder or mental retardation, but considerably higher than for blindness, stuttering, dyslexia, and epilepsy (all roughly twice as likely to be victims of such crimes), and even higher than for the loss of hearing, brain injury, or speech or physical disabilities.

Looking at covariate, family separation, having a teenage mother, or being in public care almost doubled the risk of being a victim of sexual crimes. Parental violence or parental substance abuse increased the risk by 40 percent, and parental unemployment for over 21 weeks increased the risk by 30 percent. Girls were nine times more likely to be victimized than boys. Living in a disadvantaged neighborhood made no difference, and living in immigrant neighborhoods actually reduced the odds of being victimized by about 30 percent.

After adjusting for other risk factors, youths with ADHD were still almost twice as likely to be victims of reported sex crimes than normally developing youths. All other youths with disabilities registered significantly lower levels of risk after adjusting for other risk factors: for those who were blind, 60 percent higher risk; for those with autism, hearing loss, or epilepsy, 40 percent higher risk. Communicative disabilities - speech disability, stuttering, and dyslexia - actually turned out to have protective effects.

This points to a need to be particularly vigilant for signs of sexual abuse among youths with ADHD.

To what extent does sex matter in the expression of ADHD symptoms and associated cognitive deficits among youths with ADHD?

A recently published meta-analysis of 54 studies by a Canadian team of researchers at the University of Quebec at Montreal suggests it makes little to no difference. A meta-analysis of 26 studies with over 5,900 youths found no significant difference in inattention symptoms, and a meta-analysis of 24 studies with over 5,500 youths likewise found no difference in hyperactivity-impulsivity symptoms. Separating out hyperactivity and impulsivity made no difference.

Given these results, it's no surprise that a meta-analysis of 15 studies with over 3,500 youths again found no significant divergence between the sexes for total ADHD symptoms. Parents and teachers differed, however, in their ratings of symptoms. Whereas parents observed no differences, teachers reported boys had slightly more inattention and hyperactive-impulsive behaviors than girls. Turning to cognitive functions, a series of meta-analyses found no significant sex differences for interference control, working memory, and planning scores. But boys performed slightly worse on inhibition and motor response inhibition. While the raw data also showed boys slightly under-performing girls on cognitive flexibility, strong evidence of publication bias made this unreliable.

The team also compared youths with ADHD and youths without ADHD. Both for females and for males, those differences in ADHD symptoms were - as would be expected - extremely large, whether for total symptoms, inattention, or hyperactivity-impulsivity. All cognitive function scores were moderately better for normally developing boys compared with boys with ADHD, and for normally developing girls compared with girls with ADHD. Yet once again, when comparing these effect sizes between girls and boys, there were no significant differences for any of the symptom and cognitive function effects.

"In other words," the authors wrote, "boys and girls with ADHD presented significantly more primary symptoms and executive and attention deficits than did their peers without ADHD, and effect sizes were not significantly different between the sexes." They concluded, "girls with ADHD do not differ from boys with ADHD in many domains of cognitive functioning, and they have significantly more severe difficulties across the executive and attentional functions measured relative to girls without ADHD. This meta-analysis is the first to examine sex differences in cognitive flexibility, working memory, and planning."

Two new studies, examining entire nationwide populations on opposite sides of the world, have just reported findings on the association between hypertensive disorders of pregnancy (HDP) and subsequent ADHD in off spring. HDP includes chronic hypertension, pre-eclampsia, pre-eclampsia superimposed on chronic hypertension, and gestational hypertension.

According to the Mayo Clinic, Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal. Left untreated, it can lead to serious complications for both mother and baby and can be fatal. This range of conditions affects more than one in twenty pregnancies worldwide. HDP hampers permeability of the placenta, which may reduce delivery of blood-borne oxygen and nutrients to the fetus, potentially affecting brain development. ADHD could thus theoretically emerge as a neurodevelopmental outcome.

To what extent is this borne out in national-wide population studies? Both Taiwan and Sweden have single-payer national health insurance systems that systematically track virtually every resident. One study team used the Taiwan National Health Insurance research database to examine a cohort of 877,233 children born between 2004 and 2008. The other study team used the Swedish national registers to explore a cohort of 1,085,024 individuals born between 1987 and 1996.

The Taiwanese study adjusted for the following covariate/confounders: year of birth, fetal sex, paternal age, maternal age, family income, urbanization level, maternal diabetes diagnosis, preterm birth, small for gestational age, and parental psychiatric disorders. The Swedish study adjusted for the calendar year of birth, offspring sex, maternal age, parity, height, body mass index, smoking, presentational diabetes, parental educational level, occupation, and marital status. In the Taiwanese population, children of mothers with hypertensive disorders during pregnancy were about 20% more likely to develop ADHD than those of mothers without such disorders. There was no significant difference between chronic hypertension and pregnancy-induced hypertension/pre-eclampsia.

In the Swedish population, children of mothers with hypertensive disorders during pregnancy were about 10% more likely to develop ADHD than those of mothers without such disorders. But the Swedish study also went a step further. It is incredibly difficult to identify all significant confounding variables. But if you have a large enough study population, one can examine the effect of restricting the analysis to siblings within the same families. In that way, one can control in large measure for familial confounding “ shared environment and heredity. In the subsample of siblings “ 1,279 exposed to HDP versus 1,607 not exposed “ those exposed to outerwear were 9% more likely to develop ADHD, but this outcome was not statistically significant.

Noting the reduced statistical power of the subsample, the authors nonetheless concluded, the magnitude of these associations might be too weak(for ADHD in particular) to be considered an important risk factor at the level of the general population  Moreover, in a separate cohort of 285,901 Swedish men born between 1982 and 1992 who attended assessments for military conscription, mildly lower cognitive scores among those exposed to HDP in uteri vanished altogether (mean difference = 0) when limited to comparisons between full siblings (1,917 exposed versus 2,044 not exposed).

To gauge the extent of stigma towards persons with ADHD, a European research team hired a company specialized in market and social research to conduct a poll of some five thousand randomly selected Germans. Just over a thousand completed the interview, representing a response rate of only one in five. The team acknowledged, “Although non-responder bias has to be considered to be important, ethical considerations prohibited the collection of any detailed information on non-respondents.” The sample had slightly more women and elderly persons, and a higher average level of educational attainment relative to the German population as a whole. Sampling weights were used to compensate for these discrepancies.

The poll relied on computer-assisted telephone interviews. Interviews began with prerecorded vignettes of either a 12-year-old child or 35-year-oldadult exhibiting core symptoms of ADHD (such as “careless mistakes in schoolwork,” “does not follow through on instructions,” “easily distracted by extraneous stimuli”, “loses things”, “leaves his place in the classroom or when sitting at the dining table”). Half of those interviewed were presented with child vignettes, and half with adult vignettes. The gender of the person described varied randomly.

On a scale of one to five, respondents were asked to indicate levels of agreement with two statements: 1. ‘‘Basically, we are all sometimes like this person. It’s just a question of how pronounced this state is.’’ 2. “All in all, the problems of Robert / Anne are abnormal.” For both child and adult vignettes, two out of three respondents agreed that “we are all sometimes like this person.” One in three respondents considered the problems depicted in the child vignettes as abnormal. That dropped to one in four in the adult vignettes.

Next, respondents were asked whether they ever had a problem like this, and whether someone among their family or close friends ever had to deal with such a problem. For both vignettes, one in four acknowledged having had a problem like this, and half said a close friend or family member had such a problem.

On the assumption that “negative emotional reactions are an important consequence of negative stereotypes, leading to separation, discrimination and status loss,” respondents were probed for their specific emotional reactions. “I feel annoyed,” “I react angrily,” and “provokes my incomprehension” were interpreted as indicating varying levels of anger.“Provokes fear” and “Makes me feel insecure” were seen as indicating fear. “I feel uncomfortable” was viewed as indicating somewhere between fear and anger. On the other hand, “I feel the need to help,” “I feel pity,” and “I feel sympathy” were interpreted as “pro-social” responses.

Pro-social reactions were by far the most common. Over two-thirds felt a need to help a child, and over half to help an adult, in such a situation. In both instances, almost half felt sympathy, and a half or more felt pity. On the other hand, a quarter of respondents in each case felt annoyed, and just under one in five felt uncomfortable. Almost one in seven reacted angrily to the child vignette, and almost one in six to the adult vignette. Fear was the least frequent emotional reaction.

In the case of adults, respondents were also asked about their willingness to accept the person described in the vignette in seven social situations:

·        Working together
·        As a neighbor
·        Marrying into the family
·        Introducing to a friend
·        Renting a room
·        Recommending for a job
old adult·        Taking care of chi

While three out of four respondents were willing to accept such persons as co-workers, only one in three would recommend them for a job. Two out of three would accept such persons as neighbors, and almost as many to marry into the family. Three out of five would very willingly introduce such persons to friends. Slightly over half would rent a room to them. But less than one in three would be willing to have such individuals take care of their own children.

Older respondents were more likely to see the problems as“abnormal” and to seek greater social distance. Women, and respondents with higher levels of education, were less likely to see the problems as abnormal and more likely to respond in pro-social ways.

Though showing most Germans to be accepting of persons with ADHD, these findings still indicate a significant degree of stigma, though less than for other psychiatric conditions such as depression, schizophrenia, or alcohol dependence.

A team of U.S. endocrinologists recently published the results of a meta-analysis examining a possible association between bisphenol A(BPA) and childhood ADHD. BPA is used in a variety of consumer products, including plastic bottles for food and drink, epoxy resins used to line cans of food, dental sealants, and the thermal receipts issued by stores.
A review of the literature found 29 rodent studies, but only three with humans. The human studies were too different from each other to be suitable for meta-analysis. One found no association between prenatal exposure and ADHD. A second found prenatal BPA exposure to be associated with teacher-reported hyperactivity in 4-year-old boys, but not girls. The third found is to be associated with hyperactivity scores in 3-year-old girls.
As the authors note, "Often, there is little human data available, particularly in the environmental toxicology/health fields, due to the time and expense of conducting epidemiological studies and the ethical barriers for human-controlled trials that involve human exposure to potentially hazardous chemicals. Thus, it is important to have methods for using animal data to inform human health hazard conclusions; indeed, animal models are traditionally used to study human health."
Twelve of the mice and rat studies, with a total of 709 rodents, were suitable for meta-analysis.
Overall these pointed to a tiny SMD effect size of 0.09, but it was not significant, with the odds of such a result being obtained by chance being almost one in four (p = 0.237). But when results from the 356 males and353 females were looked at separately, a significant sex difference emerged. There was essentially no effect on female rodents, with an effect size of -0.07and a 95% confidence interval of -0.27 to 0.14, widely spanning the zero mark, rendering the result statistically non-significant. Among male rodents, however, there was a small but statistically significant effect size (0.24), with a 95%confidence interval from 0.04 to 0.45. The odds of obtaining this outcome by chance were only one in 50 (p = .02).
This result must be viewed with caution, as rodent physiology often differs substantially from that of humans. The authors, therefore, conclude, "early BPA exposure is associated with a presumed hazard of hyperactivity in humans. Our conclusion is based on 'moderate' levels of evidence for the human and 'high' levels of evidence for animal literature."

A working group of the International League Against Epilepsy(ILAE), consisting of twenty experts spanning the globe (U.S., U.K., France, Germany, Japan, India, South Africa, Kenya, Brazil), recently published "consensus paper" summarizing and evaluating what is currently known about comorbid epilepsy with ADHD, and best practices.

ADHD is two to five times more prevalent among children with epilepsy. The authors suggest that ADHD is underdiagnosed in children with epilepsy because its symptoms are often attributed either to epilepsy itself or to the effects of antiepileptic drugs (AEDs).

The working group did a systematic search of the English-language research literature. It then reached a consensus on practice recommendations, graded on the strength of the evidence.

Three recommendations were graded A, indicating they are well-established by evidence:
·        Children with epilepsy with comorbid intellectual and developmental disabilities are at increased risk of ADHD.
·        There is no increased risk of ADHD in boys with epilepsy compared to girls with epilepsy.
·        The anticonvulsant valproate can exacerbate attentional issues in children with childhood absence epilepsy (absence seizures look like staring spells during which the child is not aware or responsive). Moreover, a single high-quality population-based study indicates that valproate use during pregnancy is associated with inattentiveness and hyperactivity in offspring.

Four more were graded B, meaning they are probably useful/predictive:
·        Poor seizure control is associated with an increased risk of ADHD.
·        Data support the ability of the Strengths and difficulties questionnaire (SDQ) to predict ADHD diagnosis in children with epilepsy: "Borderline or abnormal SDQ total scores are highly correlated with the presence of a validated psychiatric diagnosis (93.6%), of which ADHD is the most common (31.7%)." The SDQ can therefore be useful as a screening tool.
·        Evidence supports the efficacy of methylphenidate in children with epilepsy and comorbid ADHD.
·        Methylphenidate is tolerated in children with epilepsy.

At the C level of being possibly useful, there is limited evidence that supports that atomoxetine is tolerated in children with ADHD and epilepsy and that the combined use of drugs for ADHD and epilepsy (polytherapy) is more likely to be associated with behavioral problems than monotherapy. In the latter instance, "Studies are needed to elucidate whether the polytherapy itself has resulted in the behavioral problems, or the combination of polytherapy and the underlying brain problem reflects difficult-to-control epilepsy, which, in turn, has resulted in the prescription of polytherapy."

All other recommendations were graded U (for Unproven), "Data inadequate or conflicting; treatment, test or predictor unproven." These included three where the evidence is ambiguous or insufficient:
·        Evidence is conflicted on the impact of early seizure onset on the development of ADHD in children with epilepsy.
·        Tolerability for amphetamine in children with epilepsy is not defined.
·        Limited evidence exists for the efficacy of atomoxetine and amphetamines in children with epilepsy and ADHD.

There were also nine U-graded recommendations based solely on expert opinion. Most notable among these:
·        Screening of children with epilepsy for ADHD beginning at age 6.
·        Reevaluation of attention function after any change in antiepileptic drug.
·        Screening should not be done within 48 hours following a seizure.
·        ADHD should be distinguished from childhood absence epilepsy based on history and an EEG with hyperventilation.
·        Multidisciplinary involvement in transition and adult ADHD clinics is essential as many patients experience challenges with housing, employment, relationships, and psychosocial wellbeing.

To gauge the extent of stigma towards persons with ADHD, a European research team hired a company specialized in market and social research to conduct a poll of some five thousand randomly selected Germans. Just over a thousand completed the interview, representing a response rate of only one in five. The team acknowledged, "Although non-responder bias has to be considered to be important, ethical considerations prohibited the collection of any detailed information on non-respondents." The sample had slightly more women and elderly persons, and a higher average level of educational attainment relative to the German population as a whole. Sampling weights we reused to compensate for these discrepancies.

The poll relied on computer-assisted telephone interviews. Interviews began with prerecorded vignettes of either an a12-year-old child or a 35-year-old adult exhibiting core symptoms of ADHD (such as "careless mistakes in schoolwork," "does not follow through on instructions," easily distracted by extraneous stimuli, "loses things", "leaves his place in the classroom or when sitting at the dining table"). Half of those interviewed were presented with child vignettes and half with adult vignettes. The gender of the person described varied randomly.

On a scale of one to five, respondents were asked to indicate levels of agreement with two statements: 1. "Basically, we are all sometimes like this person. It's just a question of how pronounced this state is." 2. "All in all, the problems of Robert / Anne are abnormal." For both child and adult vignettes, two out of three respondents agreed that "we are all sometimes like this person." One in three respondents considered the problems depicted in the child vignettes as abnormal. That dropped to one in four in the adult vignettes.

Next, respondents were asked whether they ever had a problem like this and whether someone among their family or close friends ever had to deal with such a problem. For both vignettes, one in four acknowledged having had a problem like this, and half said a close friend or family member had such a problem.

On the assumption that "negative emotional reactions are an important consequence of negative stereotypes, leading to separation, discrimination and status loss," respondents were probed for their specific emotional reactions. "I feel annoyed," " react angrily," and" provokes my incomprehension" were interpreted as indicating varying levels of anger. "Provokes fear" and "Makes me feel insecure" were seen as indicating fear. "I feel uncomfortable" was viewed as indicating somewhere between fear and anger. On the other hand, "I feel the need to help," "I feel pity," and "I feel sympathy" were interpreted as "pro-social" responses.

Pro-social reactions were by far the most common. Over two-thirds felt a need to help a child, and over half to help an adult, in such a situation. In both instances, almost half felt sympathy, and a half or more felt pity. On the other hand, a quarter of respondents in each case felt annoyed, and just under one in five felt uncomfortable. Almost one in seven reacted angrily to the child vignette, and almost one in six to the adult vignette. Fear was the least frequent emotional reaction.

In the case of adults, respondents were also asked about their willingness to accept the person described in the vignette in seven social situations:

·      Working together
·      As a neighbor
·      Marrying into the family
·      Introducing to a friend
·      Renting a room
·      Recommending for a job
·      Taking care of children

While three out of four respondents were willing to accept such persons as co-workers, only one in three would recommend them for a job. Two out of three would accept such persons as neighbors, and almost as many to marry into the family. Three out of five would very willingly introduce such persons to friends. Slightly over half would rent a room to them. But less than one in three would be willing to have such individuals take care of their children.

Older respondents were more likely to see the problems as "abnormal" and to seek greater social distance. Women, and respondents with higher levels of education, were less likely to see the problems as abnormal and more likely to respond in pro-social ways.

Though showing most Germans to be accepting of persons with ADHD, these findings still indicate a significant degree of stigma, though less than for other psychiatric conditions such as depression, schizophrenia, or alcohol dependence.