Faculty Bibliography
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Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis
There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
PMID: 34635194
ISSN: 1469-8978
CID: 5091852
Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)
BACKGROUND:The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS:The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. RESULTS:Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. LIMITATIONS/CONCLUSIONS:Cross-sectional and anonymous design. CONCLUSIONS:Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
PMCID:8486586
PMID: 34606810
ISSN: 1573-2517
CID: 5099492
World psychiatry : official journal of the World Psychiatric Association (WPA). 2021:20(3):417-436.DOI: 10.1002/wps.20894
Risk and protective factors for mental disorders beyond genetics: an evidence-based atlas
Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer-tain. We conducted a "meta-umbrella" systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer's disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.
PMCID:8429329
PMID: 34505386
ISSN: 1723-8617
CID: 5067162
A Practical, Evidence-informed Approach to Managing Stimulant-Refractory Attention Deficit Hyperactivity Disorder (ADHD)
Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.
PMID: 34403134
ISSN: 1179-1934
CID: 5091332
Association between anxiety and hypertension in adults: A systematic review and meta-analysis
We assessed the association between anxiety and hypertension in adults via a systematic review/meta-analysis. We searched PubMed, Ovid, and PsycINFO through 27 March 2020 with no language or publication type restrictions and systematically contacted study authors for unpublished information/data. We meta-analysed 59 studies including a total of 4,012,775 participants. Study quality was rated with the Newcastle-Ottawa Scale and random-effects analyses were performed. A significant anxiety-hypertension association was found in cross-sectional (OR = 1.37, 95 % CI = 1.21-1.54) and prospective studies (OR = 1.40, 95 % CI = 1.23-1.59). In sensitivity analyses, results were influenced by method of hypertension diagnosis, but not by study quality, method of anxiety diagnosis, study population, and effect size type. In subgroup analyses, study location, in particular country economic status, but not participant age, influenced the results. Longitudinal data and theoretical literature indicate that anxiety may precede hypertension. These findings have important clinical implications for the early detection and treatment of both anxiety and hypertension. Suggestions for future research are discussed.
PMID: 34481847
ISSN: 1873-7528
CID: 5011852
The World Federation of ADHD International Consensus Statement: 208 Evidence-based Conclusions about the Disorder
BACKGROUND:Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. METHODS:We reviewed studies with more than 2,000 participants or meta-analyses from five or more studies or 2,000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. RESULTS:We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 79 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 362 people who have read this document and agree with its contents. CONCLUSIONS:Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
PMID: 33549739
ISSN: 1873-7528
CID: 4779222
Journal of the American Academy of Child & Adolescent Psychiatry. 2021:60(9):1056-1058.DOI: 10.1016/j.jaac.2021.02.015
Editorial: For Adolescents With Subthreshold Depression, Is an Ounce of Prevention Worth a Pound of Cure? [Editorial]
PMID: 33667603
ISSN: 1527-5418
CID: 4802002
Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study
BACKGROUND:Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood. METHODS:We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD. FINDINGS/RESULTS:4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors. INTERPRETATION/CONCLUSIONS:This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD. FUNDING/BACKGROUND:Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
PMID: 34242595
ISSN: 2215-0374
CID: 4933662
Setting the Foundations of Developmental Precision Psychiatry for ADHD [Comment]
PMID: 34383563
ISSN: 1535-7228
CID: 5010832
Journal of child psychology & psychiatry & allied disciplines. 2021:62(8):922-936.DOI: 10.1111/jcpp.13337
Research Review: A systematic review and meta-analysis of sex/gender differences in social interaction and communication in autistic and nonautistic children and adolescents
BACKGROUND:Evidence increasingly suggests that ASD manifests differently in females than males. Previous reviews investigating sex/gender differences in social interaction and social communication have focused at the level of broad constructs (e.g. comparing algorithm scores from pre-existing diagnostic instruments) and have typically reported no significant differences between males and females. However, a number of individual studies have found sex/gender differences in narrow construct domains. METHODS:We conducted a systematic review and random effects model meta-analyses (in January 2019 and updated January 2020) that investigated sex/gender differences in narrow construct measures of social communication and interaction in autistic and nonautistic children and adolescents, and adults. Study quality was appraised using the Appraisal Tool for Cross-Sectional Studies (AXIS, BMJ Open, 6, 2016, 1). RESULTS:Across 16 studies (including 2,730 participants), the analysis found that female (vs. male) individuals with ASD had significantly better social interaction and social communication skills (SMD = 0.39, p < .001), which was reflective of a similar sex/gender profile in nonautistic individuals (SMD = 0.35, p < .001). Nonautistic males had significantly better social interaction and communication than males with ASD (SMD = 0.77, p < .001). Nonautistic females also had significantly better social interaction and communication than females with ASD (SMD = 0.72, p  <.001). Nonautistic males had better social interaction and communication than females with ASD, though this difference was not significant (SMD = 0.30, p = .07). CONCLUSIONS:This systematic review and meta-analysis highlighted important sex/gender differences in social interaction and communication for individuals with ASD, likely not captured by pre-existing diagnostic instruments, which potentially contribute to the under recognition of autism in females, and may need to be reflected in the diagnostic process.
PMID: 33137209
ISSN: 1469-7610
CID: 4661512
