Faculty Bibliography

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with disordered eating, especially addictive-like eating behavior (i.e., binge eating, food addiction, loss of control overeating). The exact mechanisms underlying this association are unclear. ADHD and addictive-like eating behavior are both associated with negative affectivity and emotion dysregulation, which we hypothesized are mediators of this relationship. The purpose of this systematic review was to review the evidence related to this hypothesis from studies assessing the relationship between childhood or adulthood ADHD symptomatology, negative affectivity, emotion dysregulation and addictive-like eating behavior. The systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations. The literature search was conducted in PubMed and PsycINFO (publication date: January 2015 to August 2020; date of search: 2nd September 2020). Out of 403 potentially relevant articles, 41 were retained; 38 publications reported that ADHD and disordered eating or addictive-like eating behavior were significantly associated, including 8 articles that suggested a mediator role of negative affectivity or emotion dysregulation. Sixteen publications reported that the association between ADHD symptomatology and disordered eating or addictive-like eating behavior differed according to gender, eating behavior and ADHD symptoms (hyperactivity, impulsivity and inattention). We discuss the practical implications of these findings and directions future research.

There is a significant knowledge gap in research on Attention-Deficit/Hyperactivity Disorder (ADHD) in older adults. Via a systematic review and meta-analysis, we aimed to investigate the prevalence of ADHD in older adults, considering different assessment methods. We searched five electronic databases up to June 26, 2020. We identified 20 relevant studies with 32 datasets providing a total sample size of 20,999,871 individuals (41,420 individuals with ADHD). The pooled prevalence estimates differed significantly across assessment methods: 2.18 % (95 % CI = 1.51, 3.16) based on research diagnosis via validated scales, 0.23 % (0.12, 0.43) relying on clinical ADHD diagnosis, and 0.09 % (0.06, 0.15) based on ADHD treatment rates. Heterogeneity was significant across studies for all assessment methods. There is a considerable number of older adults with elevated levels of ADHD symptoms as determined via validated scales, and the prevalence of treated ADHD is less than half of the prevalence of clinically diagnosed ADHD. This highlights the need for increased awareness of ADHD clinical diagnosis and treatment in older adults.

A systematic review with meta-analysis was performed to: 1) estimate the prevalence of both mental and physical health problems in older offenders; 2) calculate relative risks for the health conditions in relation to non-offender older adults and; 3) explore the potential confounding role of several variables. We searched five databases up to August 2019. Studies involving offenders older than 50 years old were included. Fifty-five publications met criteria. The pooled prevalence for 18 mental and 28 physical health problems was calculated. In comparison with non-offender older adults, older offenders showed significantly higher risk for Hypertension (RR = 1.16, CI = 1.1, 1.2), Cardiovascular Diseases (RR = 1.24, CI = 1.09, 1.41), Respiratory diseases (RR = 1.75, CI = 1.29, 2.35), and Arthritis (RR = 1.19, CI = 1.12, 1.25). Heterogeneity was significant for all meta-analyses and partially explained by the confounding effect of country, the diagnosis assessment method, and the sample characteristics. Future research should include comparison groups of non-offender older adults and use longitudinal study designs to identify risk factors that can be targeted in preventive programmes.

OBJECTIVE/UNASSIGNED:To conduct a systematic review of studies assessing the relationship between exposure to pesticides and ADHD or Autism Spectrum Disorder (ASD). METHODS/UNASSIGNED:Based on a pre-registered protocol in PROPSERO (CRD42018107847), we searched PubMed, Ovid databases, and ISI Web of Knowledge with no date/language/document type restrictions, up to May 2019. The Newcastle Ottawa Scale was used to assess study quality. RESULTS/UNASSIGNED:Among the 29 retained studies, 13 focused on ADHD, 14 on ASD, and two on both disorders. Ten studies reported a significant association between exposure to pesticides and ADHD/ADHD symptoms and 12 studies found a significant association with ASD/ASD traits. The strengths of the association and the possible confounders controlled for varied substantially across studies. CONCLUSION/UNASSIGNED:Whilst there is some evidence suggesting a possible link between pesticides and ADHD/ASD, heterogeneity across studies prevents firm conclusions. We provide methodological indications for future studies.

BACKGROUND:Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring. OBJECTIVES/OBJECTIVE:The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding. METHODS:We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies. RESULTS:Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers. CONCLUSION/CONCLUSIONS:The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.

BACKGROUND:The use of antidepressants in children and adolescents remains controversial. We examined trends over time and variation in antidepressant prescribing in children and young people in England and whether the drugs prescribed reflected UK licensing and guidelines. METHODS AND FINDINGS/RESULTS:QResearch is a primary care database containing anonymised healthcare records of over 32 million patients from more than 1,500 general practices across the UK. All eligible children and young people aged 5-17 years in 1998-2017 from QResearch were included. Incidence and prevalence rates of antidepressant prescriptions in each year were calculated overall, for 4 antidepressant classes (selective serotonin reuptake inhibitors [SSRIs], tricyclic and related antidepressants [TCAs], serotonin and norepinephrine reuptake inhibitors [SNRIs], and other antidepressants), and for individual drugs. Adjusted trends over time and differences by social deprivation, region, and ethnicity were examined using Poisson regression, taking clustering within general practitioner (GP) practices into account using multilevel modelling. Of the 4.3 million children and young people in the cohort, 49,434 (1.1%) were prescribed antidepressants for the first time during 20 million years of follow-up. Males made up 52.0% of the cohorts, but only 34.1% of those who were first prescribed an antidepressant in the study period. The largest proportion of the cohort was from London (24.4%), and whilst ethnicity information was missing for 39.5% of the cohort, of those with known ethnicity, 75.3% were White. Overall, SSRIs (62.6%) were the most commonly prescribed first antidepressant, followed by TCAs (35.7%). Incident antidepressant prescribing decreased in 5- to 11-year-olds from a peak of 0.9 in females and 1.6 in males in 1999 to less than 0.2 per 1,000 for both sexes in 2017, but incidence rates more than doubled in 12- to 17-year-olds between 2005 and 2017 to 9.7 (females) and 4.2 (males) per 1,000 person-years. The lowest prescription incidence rates were in London, and the highest were in the South East of England (excluding London) for all sex and age groups. Those living in more deprived areas were more likely to be prescribed antidepressants after adjusting for region. The strongest trend was seen in 12- to 17-year-old females (adjusted incidence rate ratio [aIRR] 1.12, 95% confidence interval [95% CI] 1.11-1.13, p < 0.001, per deprivation quintile increase). Prescribing rates were highest in White and lowest in Black adolescents (aIRR 0.32, 95% CI 0.29-0.36, p < 0.001 [females]; aIRR 0.32, 95% CI 0.27-0.38, p < 0.001 [males]). The 5 most commonly prescribed antidepressants were either licensed in the UK for use in children and young people (CYP) or included in national guidelines. Limitations of the study are that, because we did not have access to secondary care prescribing information, we may be underestimating the prevalence and misidentifying the first antidepressant prescription. We could not assess whether antidepressants were dispensed or taken. CONCLUSIONS:Our analysis provides evidence of a continuing rise of antidepressant prescribing in adolescents aged 12-17 years since 2005, driven by SSRI prescriptions, but a decrease in children aged 5-11 years. The variation in prescribing by deprivation, region, and ethnicity could represent inequities. Future research should examine whether prescribing trends and variation are due to true differences in need and risk factors, access to diagnosis or treatment, prescribing behaviour, or young people's help-seeking behaviour.

BACKGROUND:Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden. METHODS:We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding. RESULTS:Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)]. CONCLUSION/CONCLUSIONS:Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.