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Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis

Zhang, Le; Yao, Honghui; Li, Lin; Du Rietz, Ebba; Andell, Pontus; Garcia-Argibay, Miguel; D'Onofrio, Brian M; Cortese, Samuele; Larsson, Henrik; Chang, Zheng
IMPORTANCE:Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety. OBJECTIVE:To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs). DATA SOURCES:PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022. STUDY SELECTION:Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD. DATA EXTRACTION AND SYNTHESIS:Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline. MAIN OUTCOMES AND MEASURES:The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest. RESULTS:Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases. CONCLUSIONS AND RELEVANCE:This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.
PMID: 36416824
ISSN: 2574-3805
CID: 5378502

Signal in the noise: Dimensions of predictability in the home auditory environment are associated with neurobehavioral measures of early infant sustained attention

Werchan, Denise M; Brandes-Aitken, Annie; Brito, Natalie H
The home auditory environment influences the development of early language abilities, and excessive noise exposure is increasingly linked with deficits in language and reading scores in children. However, fewer studies have considered the role of noise exposure in shaping the development of attentional processing in early infancy, a foundational neurocognitive skill relevant for learning. Here, we used passive at-home auditory recording to investigate how multiple dimensions of infants' home auditory environments, including both the quantity and the predictability of auditory input, impacts neural and behavioral measures of sustained attention in a sociodemographically diverse sample of 3-month-old infants (N = 98 infants, 62 males; age M = 3.48 months, SD = 0.39; 52% Hispanic/Latino). Results indicated that infants who were exposed to more predictable patterns of auditory input in the home demonstrated longer overall time in sustained attention during laboratory assessments. In addition, infants' who experienced more predictable auditory input also demonstrated greater relative increases in electroencephalography frontal theta power during periods of sustained attention, a neural marker relevant to information processing and attentional control. These findings provide novel evidence into the importance of the predictability of early environmental inputs in shaping developing cortical circuitry and attentional systems from the first months of postnatal life.
PMID: 36282744
ISSN: 1098-2302
CID: 5359112

Male Caregivers and Engagement in a Family Strengthening Program for Child Disruptive Behavior Disorders

Acri, Mary; Chun, Yung; Yin, Shuya; Fang, Cao; Joe, Sean; McKay, Mary
Awareness and interest in involving male caregivers in child mental health treatment has grown, especially for youth with disruptive behavior disorders like oppositional defiant disorder (ODD). The purpose of this study was to examine the relationship between male caregiver involvement and treatment engagement for child ODD. Children (n = 122) ages 7-11 and their caregivers participated in the 4 Rs 2 Ss Strengthening Families Program for child-onset ODD. Families were compared based on male caregiver presence. Families with a male caregiver were significantly more resourced with respect to income, educational status, and food security. Additionally, they were over three times less likely to drop out of the program than those without a male caregiver. The presence of a male caregiver was associated with increased resources and higher rates of engagement in services than single, female-headed families. Future research is needed to discern the underlying mechanisms of this association.
PMID: 35362804
ISSN: 1573-2789
CID: 5206082

The Neuroscience-based Nomenclature Child & Adolescent (NbN C&A) for Psychotropic Medications: Innovation in Progress [Editorial]

Cortese, Samuele; Singh, Manpreet Kaur; Novins, Douglas K
To address the issues with the current nomenclature of psychotropic agents, which may be misleading or confusing, the Neuroscience-based Nomenclature (NbN) started being developed in 2009. It was introduced as one approach to the classification of pharmacological treatments based on a medication's putative psychopharmacological mechanisms of action derived from preclinical and clinical studies. In 2018, the NbN-Child & Adolescent (NbN C&A) was released. Since then, the NbN C&A has been refined, and its website and app (https://nbnca.com/) have been implemented. JAACAP encourages its authors and readers to consider utilizing the NbN C&A and to keep abreast of its developments over time. This is in line with the core missions of the Journal: to contribute to the translation and implementation of the most up-to-date science into real-world clinical practice. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.
PMID: 35697264
ISSN: 1527-5418
CID: 5470402

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on oppositional defiant disorder and impaired functioning among children in Uganda: analysis of a cluster randomized trial from the SMART Africa-Uganda scale-up study (2016-2022)

Brathwaite, Rachel; Ssewamala, Fred M; Sensoy Bahar, Ozge; McKay, Mary M; Neilands, Torsten B; Namatovu, Phionah; Kiyingi, Joshua; Zmachinski, Lily; Nabayinda, Josephine; Huang, Keng-Yen; Kivumbi, Apollo; Bhana, Arvin; Mwebembezi, Abel; Petersen, Inge; Hoagwood, Kimberly
BACKGROUND:Oppositional Defiant Disorders (ODDs) and other Disruptive Behavior Disorders (DBDs) are common among children and adolescents in poverty-impacted communities in sub-Saharan Africa. Without early intervention, its progression into adulthood can result in dire consequences. We examined the impact of a manualized family strengthening intervention called Amaka Amasanyufu designed to reduce ODDs and other DBDs among school-going children residing in low-resource communities in Uganda. METHODS:We used longitudinal data from the SMART Africa-Uganda study (2016-2022). Public primary schools were randomized to: (1) Control condition (receiving usual care comprising generalized psychosocial functioning literature), 10 schools; (2) intervention delivered via parent peers (Amaka-parents), 8 schools or; (3) intervention delivered via community healthcare workers (Amaka-community), 8 schools. All the participants were blinded. At baseline, 8- and 16-weeks postintervention initiation, caregivers completed the Iowa Conners Scale, which measured Oppositional Defiant Disorder (ODD) and Impairment Rating Scale to evaluate children's overall impairment and impaired functioning with peers, siblings, and parents; impaired academic progress, self-esteem, and family functioning. Three-level linear mixed-effects models were fitted to each outcome. Pairwise comparisons of postbaseline group means within each time point were performed using Sidak's adjustment for multiple comparisons. Only children positive for ODD and other DBDs were analyzed. RESULTS:Six hundred and thirty-six children screened positive for ODDs and other DBDs (Controls: n = 243; Amaka-parents: n = 194; Amaka-community: n = 199). At 8 weeks, Amaka-parents' children had significantly lower mean scores for overall impairment compared to controls, (mean difference: -0.71, p = .001), while Amaka-community children performed better on ODD (mean difference: -0.84, p = .016). At 16 weeks, children in both groups were performing better on ODD and IRS than controls, and there were no significant differences between the two intervention groups. CONCLUSIONS:The Amaka Amasanyufu intervention was efficacious in reducing ODD and impaired functioning relative to usual care. Hence, the Amaka Amasanyufu intervention delivered either by Amaka-community or Amaka-parents has the potential to reduce negative behavioral health outcomes among young people in resource-limited settings and improve family functioning. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov, ID: NCT03081195. Registered on 16 March 2017.
PMID: 34989404
ISSN: 1469-7610
CID: 5107242

Cerebro-cerebellar Dysconnectivity in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Wang, Pan; Wang, Jianlin; Jiang, Yuan; Wang, Zedong; Meng, Chun; Castellanos, F Xavier; Biswal, Bharat B
OBJECTIVE:Abnormal cerebellar development has been implicated in Attention-Deficit/Hyperactivity Disorder (ADHD), although cerebro-cerebellar functional connectivity (FC) has yet to be examined in ADHD. Our objective is to investigate the disturbed cerebro-cerebellar FC in children and adolescents with ADHD. METHOD/METHODS:We analyzed the dataset of 106 individuals with ADHD (68 children, 38 adolescents) and 62 healthy comparisons (34 children, 28 adolescents) from the publicly available ADHD-200 dataset. We identified seven cerebellar sub-regions based on cerebro-cerebellar FC and subsequently obtained the FC maps of cerebro-cerebellar networks. Main effects of ADHD and age and their interaction were examined using two-way analysis of variance. RESULTS:Compared to comparisons, ADHD showed higher cerebro-cerebellar FC in superior temporal gyrus within the somatomotor network. Interactions of diagnosis and age were identified in the supplementary motor area and postcentral gyrus within the somatomotor network and middle temporal gyrus within the ventral attention network. Follow-up Pearson correlation analysis revealed decreased cerebro-cerebellar FC in these regions with increasing age in comparisons, while the opposite pattern of increased cerebro-cerebellar FC occurred in ADHD. CONCLUSION/CONCLUSIONS:Increased cerebro-cerebellar FC in superior temporal gyrus within the somatomotor network could underlie impairments in cognitive control and somatic motor function in ADHD. In addition, increasing cerebro-cerebellar FC in older participants with ADHD suggests that enhanced cerebellar involvement may compensate for dysfunctions of the cerebral cortex in ADHD.
PMID: 35661770
ISSN: 1527-5418
CID: 5236272

Predictors of longer-term depression trajectories during the COVID-19 pandemic: a longitudinal study in four UK cohorts

Rosa, Lara; Godwin, Hayward J; Cortese, Samuele; Brandt, Valerie
BACKGROUND:The COVID-19 pandemic has caused an increase in mental ill health compared with prepandemic levels. Longer-term trajectories of depression in adults during the pandemic remain unclear. OBJECTIVE:We used latent growth curve modelling to examine individual trajectories of depression symptoms, and their predictors, beyond the early stage of the pandemic. METHODS:Data were collected in three waves in May 2020, September/October 2020 and February/March 2021 in four UK cohorts (Millennium Cohort Study, Next Steps cohort, British Cohort and National Child Development Study). We included n=16 978 participants (mean age at baseline: 20, 30, 50 and 62, respectively). Self-reported depressive symptoms were the study outcome. FINDINGS/RESULTS:Symptoms of depression were higher in younger compared with older age groups (d=0.7) across all waves. While depressive symptoms remained stable from May 2020 to Autumn 2020 overall (standardized mean difference (SMD)=0.03, 95% CI 0.02 to 0.04), they increased in all age groups from May 2020 to Spring 2021 (SMD=0.12, 95% CI 0.11 to 0.13). Feelings of loneliness were the strongest predictor and concurrent correlate of increasing depressive symptoms across all cohorts, prepandemic mental health problems and having a long-term illness were also significantly associated with an increase in depression symptoms across all ages. By contrast, compliance with social distancing measures did not predict an increase in depression symptoms. CONCLUSIONS:Feeling lonely and isolated had a large effect on depression trajectories across all generations, while social distancing measures did not. CLINICAL IMPLICATIONS/CONCLUSIONS:These findings highlight the importance of fostering the feeling of connectedness during COVID-19-related distancing measures.
PMID: 35902216
ISSN: 1468-960x
CID: 5276892

Predictors of and barriers to receipt of advance premium tax credits

Acri, Mary; Beck, Abaki; Chun, Yung; Shannon, Mary; Roll, Stephen; Grinstein-Weiss, Michal
OBJECTIVES/OBJECTIVE:The Advance Premium Tax Credit (APTC) is designed to remedy lack of health insurance due to cost; however, approximately 30 million Americans remain without health insurance and millions of households leave billions in tax credits unclaimed each year. A prerequisite of APTC is to file one's taxes; however, few studies have examined tax filing and APTC jointly. This study examined the relationship between tax filing and applying for APTC, as well as perceived barriers to and sociodemographic characteristics associated with applying for the APTC. STUDY DESIGN/METHODS:Descriptive study. METHODS:Researchers surveyed 372 Marketplace-insured members who were eligible for APTC. RESULTS:Most of the sample filed personal taxes in 2019 and planned to file taxes in 2020, yet only 23% applied for the APTC in 2019, and 26.3% were planning to apply in 2020. Most commonly, respondents were not going to apply because they believed they were not eligible (53.5%), they did not know about the APTC (15.8%), and they did not know whether they were eligible (9.9%). Logistic regression modeling found that employment, income, and race were significantly associated with applying for the APTC. CONCLUSIONS:Barriers to applying for the APTC were unrelated to tax filing and were specific to a lack of knowledge about the APTC and eligibility. These results indicate the need to build knowledge and awareness of the APTC and eligibility and to target groups least likely to apply. Implications and future directions are discussed.
PMID: 36374617
ISSN: 1936-2692
CID: 5371532

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis

Salanti, Georgia; Peter, Natalie; Tonia, Thomy; Holloway, Alexander; White, Ian R; Darwish, Leila; Low, Nicola; Egger, Matthias; Haas, Andreas D; Fazel, Seena; Kessler, Ronald C; Herrman, Helen; Kieling, Christian; De Quervain, Dominique J F; Vigod, Simone N; Patel, Vikram; Li, Tianjing; Cuijpers, Pim; Cipriani, Andrea; Furukawa, Toshi A; Leucht, Stefan; Sambo, Abdulkadir Usman; Onishi, Akira; Sato, Akira; Rodolico, Alessandro; Oliveira Solis, Ana Cristina de; Antoniou, Anastasia; Kapfhammer, Angelika; Ceraso, Anna; O'Mahony, Aoife; Lasserre, Aurélie M; Ipekci, Aziz Mert; Concerto, Carmen; Zangani, Caroline; Igwesi-Chidobe, Chinonso; Diehm, Christina; Demir, Dicle Dilay; Wang, Dongfang; Ostinelli, Edoardo Giuseppe; Sahker, Ethan; Beraldi, Gabriel Henrique; Erzin, Gamze; Nelson, Harrison; Elkis, Helio; Imai, Hissei; Wu, Hui; Kamitsis, Ilias; Filis, Ioannis; Michopoulos, Ioannis; Bighelli, Irene; Hong, James S W; Ballesteros, Javier; Smith, Katharine A; Yoshida, Kazufumi; Omae, Kenji; Trivella, Marialena; Tada, Masafumi; Reinhard, Matthias A; Ostacher, Michael J; Müller, Monika; Jaramillo, Nathalia Gonzalez; Ferentinos, Panagiotis P; Toyomoto, Rie; Cortese, Samuele; Kishimoto, Sanae; Covarrubias-Castillo, Sergio A; Siafis, Spyridon; Thompson, Trevor; Karageorgiou, Vasilios; Chiocchia, Virginia; Zhu, Yikang; Honda, Yukiko
BACKGROUND:To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE:To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES:Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION:Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION:An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS:In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS:The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION:Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE:Swiss National Science Foundation. (PROSPERO: CRD42020180049).
PMCID:9579966
PMID: 36252247
ISSN: 1539-3704
CID: 5470422

The immune phenotype of perinatal anxiety

Sherer, Morgan L; Voegtline, Kristin M; Park, Han-Sol; Miller, Kristen N; Shuffrey, Lauren C; Klein, Sabra L; Osborne, Lauren M
BACKGROUND:Immune dysregulation has been linked to both psychiatric illness and pregnancy morbidity, including perinatal depression, but little is known about the immune phenotype of perinatal anxiety. Here, we sought to identify the unique immune profile of antenatal anxiety. MATERIALS AND METHODS/METHODS:Pregnant women (n = 107) were followed prospectively at 2nd and 3rd trimesters (T2, T3) and 6 weeks postpartum (PP6). Each visit included a blood draw and psychological evaluation, with clinical anxiety assessed using the Spielberg State-Trait Anxiety Scale. We enrolled both healthy controls and participants with anxiety alone; those with comorbid depression were excluded. Multiplex cytokine assays and flow cytometry were used to examine the association of anxiety symptoms with secreted immune markers and PBMC-derived immune cells. RESULTS:cells in the postpartum as compared with Non-Anxiety women. CONCLUSION/CONCLUSIONS:These data suggest that the immune response throughout the antenatal period differs for women with anxiety symptoms compared to those without, suggestive of a unique immune phenotype of perinatal anxiety.
PMID: 36115543
ISSN: 1090-2139
CID: 5340682