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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."

A research team used Sweden's Total Population Register to identify all 445,790 individuals born in the five years from 1987 through 1991 who remained alive and resident in Sweden during the follow-up period (2001-2014).

The team then consulted the National Patient Register (NPR) to identify the 3,534 members of this cohort who received an ADHD diagnosis before turning eighteen.

Next, they used two national registers (the NPR and the Swedish Prescribed Drug Register) to identify those who also received an ADHD diagnosis or medication prescription in adulthood. They categorized these as "ADHD persisters," as opposed to "ADHD remitters," who did not seek further ADHD-related contact with healthcare services in adulthood.

Using national personal identification numbers, they were also able to link this data to demographic data in the Longitudinal Integration Database for Health Insurance and Labor Market Studies and to cost data in the Cost Per Patient database.

The team adjusted for known confounders. Parental education and family income were used as proxies for socioeconomic status. They also adjusted fr sex and year of birth.

Of the 3,534 individuals who received an ADHD diagnosis in childhood, 62 percent were classified as persisters and 38 percent as remitters in young adulthood.

The mean annual healthcare expenditure for individuals with a childhood ADHD diagnosis was three times higher than for those without such a diagnosis: $1,223 versus $418(after conversion from Swedish króna into U.S. dollars). Broken down further, it was $854 versus $226 for inpatient care, $209 versus $104 for outpatient care, and $158 versus $87 for medication.

Focusing just on the ADHD group, the mean annual healthcare expenditure for those whose ADHD care persisted into young adulthood was 74 percent greater than for remitters:$1,456 versus $837 (which was still twice as high as for no childhood diagnosis). Broken down further, it was $1,014 versus $589 for inpatient care,$246 versus $151 for outpatient care, and $196 versus $96 for medication.

Inpatient care was the main driver of costs in individuals with a childhood ADHD diagnosis. Delving deeper into causes, almost a third of inpatient care was associated with drug or alcohol abuse, 15 percent with injuries, 14 percent with various somatic ailments, and the remainder with comorbid psychiatric disorders(primarily autism, schizophrenia, depression, anxiety).

The authors emphasized that "A novel finding in this study was that individuals with childhood ADHD who no longer had ADHD-related contact with healthcare services in adulthood (remitters) continued to show severe psychiatric and somatic health problems, often leading to hospitalization. This group of individuals showed intermediate profiles on outcomes, with values lower than the ADHD persistent group but higher than the non-ADHD group."

A Swedish-Danish-Dutch team used the Swedish Medical Birth Register to identify the almost 1.7 million individuals born in the country between 1980 and 1995. Then, using the Multi-Generation Register, they identified 341,066 pairs of full siblings and 46,142 pairs of maternal half-siblings, totaling 774,416 individuals.

The team used the National Patient Register to identify diagnoses of ADHD, as well as neurodevelopmental disorders (autism spectrum disorder, developmental disorders, intellectual disability, motor disorders), externalizing psychiatric disorders (oppositional defiant and related disorders, alcohol misuse, drug misuse), and internalizing psychiatric disorders (depression, anxiety disorder, phobias, stress disorders, obsessive-compulsive disorder).

The team found that ADHD was strongly correlated with general psychopathology overall (r =0.67), as well as with the neurodevelopmental (r = 0.75), externalizing (r =0.67), and internalizing (r = 0.67) sub factors.

To tease out the effects of heredity, shared environment, and non-shared environment, a multivariate correlation model was used. Genetic variables were estimated by fixing them to correlate between siblings at their expected average gene sharing (0.5for full siblings, 0.25 for half-siblings). Non-genetic environmental components shared by siblings (such as growing up in the same family) were estimated by fixing them to correlate at 1 across full and half-siblings. Finally, non-shared environmental variables were estimated by fixing them to correlate at zero across all siblings.

This model estimated the heritability of the general psychopathology factor at 49%, with the contribution of the shared environment at 7 percent and the non-shared environment at 44%. After adjusting for the general psychopathology factor, ADHD showed a significant and moderately strong phenotypic correlation with the neurodevelopmental-specific factor (r = 0.43), and a significantly smaller correlation with the externalizing-specific factor (r = 0.25).

For phenotypic correlation between ADHD and the general psychopathology factor, genetics explained 52% of the total correlation, the non-shared environment 39%, and the shared familial environment only 9%. For the phenotypic correlation between ADHD and the neurodevelopmental-specific factor, genetics explained the entire correlation because the other two factors had competing effects that canceled each other out. For the phenotypic correlation between ADHD and the externalizing-specific factor, genetics explained 23% of the correlation, shared environment 22%, and non-shared environment 55%.

The authors concluded that "ADHD is more phenotypically and genetically linked to neurodevelopmental disorders than to externalizing and internalizing disorders, after accounting for a general psychopathology factor. ... After accounting for the general psychopathology factor, the correlation between ADHD and the neurodevelopmental-specific factor remained moderately strong, and was largely genetic in origin, suggesting substantial unique sharing of biological mechanisms among disorders. In contrast, the correlation between ADHD and the externalizing-specific factor was much smaller and was largely explained by-shared environmental effects. Lastly, the correlation between ADHD and the internalizing subfactor was almost entirely explained by the general psychopathology factor. This finding suggests that the comorbidity of ADHD and internalizing disorders are largely due to shared genetic effects and non-shared environmental influences that have effects on general psychopathology."

An international team of researchers recently published the first meta-analysis of studies examining the prevalence of ADHD in older adults, with a particular focus on those fifty and older. They also looked at rates of treatment.

Since clinical evaluations a reconsidered the gold standard in diagnosing ADHD, and validated rating scales are considered more of a preliminary screening tool, the team distinguished between the two and ran two separate meta-analyses:

·        Using validated ADHD rating scales. Combining nine studies with just over 32,000 participants, the team reported a prevalence of 2.2 percent. However, since the studies were not uniform in fixing the minimum end of their age ranges, constraining the results to persons 50 and older lowered the prevalence to 1.5 percent.

·        Using clinical diagnoses. Combining seven studies with 11.7 million participants, they found a crude prevalence of 0.23 percent, which, after removing persons under 50, was adjusted to 0.19 percent. Limiting the results to the use of national registries further reduced the prevalence to 0.14 percent.

That means there's an order of magnitude (tenfold) difference between the two estimates of prevalence.

Recognizing that clinical diagnoses are the preferred means of diagnosis, the authors wrote, "methodological aspects need to be considered when interpreting the gap between the pooled prevalence estimates based on different assessment methods. The estimates from studies based on research diagnosis [ADHD rating scales] may overestimate the prevalence of ADHD in older adults. ... Thus, screening assessment tools for ADHD should only be used as the first step of a more comprehensive clinical ADHD assessment."

On the other hand, the authors also see an indication "that clinicians, to some extent, might fail to recognize and properly treat ADHD symptoms in older adults. Clinical presentation of ADHD may change with age, with inattentive symptoms becoming more prevalent than hyperactivity and impulsivity."

The team also performed a third meta-analysis, to look at ADHD pharmacological treatment rates among older adults. For this one, they pooled four studies encompassing over 9.2 million persons. After constraining the results to those fifty and older, they found a prevalence of only 0.02%. This points to a wide gap between rates of diagnosis and rates of treatment, even after noting that only one of the studies included data on non-pharmacological treatment.

The aim of behavioral parent training is to improve the child's behavior through improved parenting. Noting that "it is unknown which of its components are most effective," a Dutch team of researchers conducted a systematic search of the peer-reviewed medical literature to identify randomized controlled trials (RCTs) suitable for meta-analysis.

Twenty-nine RCTs with a combined total of 2,345 participants met the criteria.

The team explored five types of outcome variables:

·        Positive parenting: behaviors such as reinforcement, monitoring, stimulating, and guiding the child.
·        Negative parenting: behaviors such as corporal punishment, harsh discipline, inconsistent parenting, and poor monitoring.
·        Parenting sense of competence: the extent to which parents perceive themselves as competent or effective in raising their child.
·        Quality of the parent-child relationship: signs of affection, support, sensitivity, and responsiveness.
and behavioral parent training aims:
·        Parental mental health: measures included parenting stress and several indices of parental psychopathologies, such as depression and anxiety.

A meta-analysis of 19 RCTs with 1,070 participants found a medium effect size improvement in positive parenting. Evidence of publication bias was borderline, but a trim-and-fill adjustment still reported a medium effect size reduction in ADHD symptoms. Similarly, limiting the meta-analysis to the 12 RCTs that were probably blinded made no difference in the outcome.

A second meta-analysis, of 15 RCTs with 878 participants, found a small-to-medium effect size reduction in negative parenting, after adjusting for publication bias. Limiting the meta-analysis to the six RCTs that were probably blinded modestly increased the effect size.

After adjusting for publication bias, a meta-analysis of 13RCTs with a combined total of 783 participants reported a small-to-medium effect size improvement in the quality of parent-child relationships. Limiting the meta-analysis to the six RCTs that were probably blinded made no difference in the outcome.

After adjusting for publication bias, a meta-analysis of 17 RCTs with a combined total of 1,083 participants reported a medium effect size improvement in parent sense of competency.

Finally, with no sign of publication bias, 23 RCTs with a combined total of 1,191 participants found a small-to-medium effect size improvement in parental mental health.

The team concluded, "Parent training had robust small- medium-sized positive effects on all parental outcomes relative to control conditions, both for unblinded and probably blinded measures. ... A reassuring finding was that effect sizes on positive parenting, negative parenting, and the parent-child relationship did not differ between probably blinded and unblinded measures, indicating that effects are not merely attributable to parents' investment affecting their assessment of outcome measures."

Modified release (MR) formulations of ADHD stimulant medications simplify adherence over immediate-release (IR) formulations, by only requiring a single dosing per day. They are also intended to reduce diversion to nonmedical usage and the development of drug abuse or dependency. Is there evidence they deliver on this promise?

There are 55 poison control centers distributed throughout the United States, and they all report through the National Poison Data System (NPDS).

A pair of researchers used the NPDS to obtain all 15,796 single-substance MR ingestion and single-substance 23,418 IR ingestion reported to poison control centers over the eleven years from January 1, 2007, through December 31, 2017. The medications were either amphetamine or methylphenidate-based.

IR ingestion was more commonly associated with more serious outcomes than were MR ingestion. No deaths were reported from MR stimulant ingestion, versus three deaths (a rate of one in 7,800 reports) from IR stimulant ingestion. While there were no observed differences between youth MR and IR ingestion about admission to critical care units, adult IR ingestion was more commonly admitted to a critical care unit than was adult MR ingestion. Moreover, adults were more commonly admitted to critical care units for both MR and IR ingestion than were youths.

Among youths, the vast majority of MR ingestion was unintentional, with only one in eleven attributed to intentions of suicide. Among adults, however, almost half were intentional, with just over a quarter attributed to intentions of suicide, and another one in six to intentional misuse.

Turning to IR ingestion, the vast majority were again unintentional among youths, with less than one in twelve attributed to suspected suicide attempts. But among adults, the majority were intentional, with almost one in three attributed to suspected suicide attempts, plus another one in five to intentional misuse.

More than four out of five IR ingestion among both youths and adults were of amphetamine medications. For MR ingestion, methylphenidate was most common in youths and amphetamine medications in adults, but only by slight margins.

The most commonly reported symptoms in adults and youths alike for both IR and MR ingestion were agitation, abnormally rapid heart rates, and high blood pressure.

The authors concluded, "More serious outcomes were associated with advancing age, intentional ingestion, and IR preparations. Higher rates of hyperadrenergic symptoms (tachycardia, agitation, and hypertension) were observed with IR ingestion."

On balance, this suggests MR formulations are safer, but both formulations are subject to abuse by a small minority of users.