Scholarlink

Objective <p>Hundreds of rare genetic variants associated with autism or intellectual disability have been identified, and many impact genes known to have a primary epigenetic/chromatin regulatory function. The objective of this study was to examine and compare behavioural profiles and longitudinal psychotropic treatment patterns in children with epigenetic/chromatin variants, other rare variants impacting neurodevelopment, or no known genetic condition.</p> Methods <p>Using electronic medical records from a pediatric psychopharmacology program for children with autism or intellectual disability, we compared clinical characteristics, longitudinal psychotropic medication profiles and side effects between those with and without a rare genetic variant, and by variant subtype [epigenetic/chromatin regulation or other variant].</p> Results <p>A total of 331 children attended 2724 unique medical visits between 2019 and 2022, with a mean of 8 follow-up visits over 3.4&#xa0;years. Nine children (3%) had variants in epigenetic/chromatin regulatory genes (EC), twenty-three children (7%) had other rare genetic variants (OTH), and the rest had no reported variant (NR, <i>n</i> = 299, 90%). Those with a rare genetic variant (EC or OTH) were more likely to have an intellectual disability and had a greater number of co-occurring physical health conditions (<i>p</i> &lt; 0.01). Overall, 66% of psychotropic medications were continued for ≥ 3 visits, while 26% were discontinued. Rates of psychotropic polypharmacy, medication patterns, behavioural challenges, and co-occurring developmental diagnoses were similar between genetic groups. Analyses uncorrected for multiple comparisons suggested those with genetic variants were more likely to experience drowsiness/sedation as a side effect (EC 33%, OTH 35%, NR 16%, <i>p</i> &lt; 0.05); weight gain as a side effect was also higher in the epigenetic/chromatin group (EC 50% vs OTH 11%).</p> Conclusion <p>Genetic classification of neurodevelopmental disorders (NDDs) may help anticipate treatment tolerability; additional prescribing considerations may be needed for those with rare variants. Current psychotropic prescribing practices do not differ across rare genetic NDD subgroups.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Psychopharmacology in children with genetic disorders of epigenetic and chromatin regulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月24日

查看全文
  • Sophia Lenz,
  • Ajilan Sivaloganathan,
  • Sarah J. Goodman,
  • Cheryl Cytrynbaum,
  • Jesiqua Rapley,
  • Emma Canning,
  • Danielle Baribeau

摘要

Objective

Hundreds of rare genetic variants associated with autism or intellectual disability have been identified, and many impact genes known to have a primary epigenetic/chromatin regulatory function. The objective of this study was to examine and compare behavioural profiles and longitudinal psychotropic treatment patterns in children with epigenetic/chromatin variants, other rare variants impacting neurodevelopment, or no known genetic condition.

Methods

Using electronic medical records from a pediatric psychopharmacology program for children with autism or intellectual disability, we compared clinical characteristics, longitudinal psychotropic medication profiles and side effects between those with and without a rare genetic variant, and by variant subtype [epigenetic/chromatin regulation or other variant].

Results

A total of 331 children attended 2724 unique medical visits between 2019 and 2022, with a mean of 8 follow-up visits over 3.4 years. Nine children (3%) had variants in epigenetic/chromatin regulatory genes (EC), twenty-three children (7%) had other rare genetic variants (OTH), and the rest had no reported variant (NR, n = 299, 90%). Those with a rare genetic variant (EC or OTH) were more likely to have an intellectual disability and had a greater number of co-occurring physical health conditions (p < 0.01). Overall, 66% of psychotropic medications were continued for ≥ 3 visits, while 26% were discontinued. Rates of psychotropic polypharmacy, medication patterns, behavioural challenges, and co-occurring developmental diagnoses were similar between genetic groups. Analyses uncorrected for multiple comparisons suggested those with genetic variants were more likely to experience drowsiness/sedation as a side effect (EC 33%, OTH 35%, NR 16%, p < 0.05); weight gain as a side effect was also higher in the epigenetic/chromatin group (EC 50% vs OTH 11%).

Conclusion

Genetic classification of neurodevelopmental disorders (NDDs) may help anticipate treatment tolerability; additional prescribing considerations may be needed for those with rare variants. Current psychotropic prescribing practices do not differ across rare genetic NDD subgroups.