Examination of Aggression and Self-injury in Children with Autism Spectrum Disorders and Serious Behavioral Problems

Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and family members. Despite its high prevalence, reaching 1/54 children and 1/45 adults in the United States, no pharmacological treatment is still directed to core symptoms of ASD, encompassing social and communication deficits, repetitive behaviors, restricted interests, and abnormal sensory processing. The purpose of this review is to provide an overview of the state-of-the-art of psychopharmacological therapy available today for ASD in children and adolescents, in order to foster best practices and to organize new strategies for future research. To date, atypical antipsychotics such as risperidone and aripiprazole represent the first line of intervention for hyperactivity, impulsivity, agitation, temper outbursts or aggression towards self or others. Tricyclic antidepressants are less prescribed because of uncertain efficacy and important side effects. SSRIs, especially fluoxetine and sertraline, may be effective in treating repetitive behaviors (anxiety and obsessive-compulsive symptoms) and irritability/agitation, while mirtazapine is more helpful with sleep problems. Low doses of buspirone have shown some efficacy on restrictive and repetitive behaviors in combination with behavioral interventions. Stimulants, and to a lesser extent atomoxetine, are effective in reducing hyperactivity, inattention and impulsivity also in comorbid ASD-ADHD, although with somewhat lower efficacy and greater incidence of side effects compared to idiopathic ADHD. Clonidine and guanfacine display some efficacy on hyperactivity and stereotypic behaviors. For several other drugs, case reports and open-label studies suggest possible efficacy, but no randomized controlled trial has yet been performed. Research in the pediatric psychopharmacology of ASD is still faced with at least two major hurdles: (a) Great interindividual variability in clinical response and side effect sensitivity is observed in the ASD population. This low level of predictability would benefit from symptom-specific treatment algorithms and from biomarkers to support drug choice; (b) To this date, no psychoactive drug appears to directly ameliorate core autism symptoms, although some indirect improvement has been reported with several drugs, once the comorbid target symptom is abated.

The increasing availability of high-potency cannabis-derived compounds and the use of synthetic cannabinoids may be responsible for severe side effects like cognitive impairment, psychosis or self-injurious behaviours (SIB). In particular, SIB like non-suicidal self-injury (NSSI) and deliberate self-harm (DSH) raise growing concern as a possible consequence of cannabis use. However, the research to date has not addressed the relationship between cannabinoid use and SIB systematically.

We conducted a systematic review on PubMed up to March 2020, using search terms related to cannabinoids and SIB.

The search yielded a total of 440 abstracts. Of those, 37 studies published between 1995 and 2020 were eligible for inclusion. Cannabinoid use was significantly associated with SIB at the cross-sectional (OR=1.569, 95%CI [1.167–2.108]) and longitudinal (OR=2.569, 95%CI [2.207–3.256]) level. Chronic use, presence of mental disorders, depressive symptoms, emotional dysregulation and impulsive traits might further increase the likelihood of self-harm in cannabis users. Synthetic cannabinoids may trigger highly destructive SIB mainly through the psychotomimetic properties of these compounds.

Cannabinoid use was associated with an increased prevalence of self-injury and may act as a causative factor with a duration-dependent manner. Emotional regulation and behavioural impulsivity functions might crucially moderate this association. Future studies should further investigate the mechanisms underlying this association, while exploring potential therapeutic applications of substances modulating the endocannabinoid system.

Studies that examine the role of factors documented before self-injurious behaviors (SIB) occur are important in establishing a temporal relationship between these factors and SIB. Using data from a population-based surveillance system of 8-year-olds with autism spectrum disorder (ASD), we: (1) explored potential associations between SIB and prenatal, perinatal, and neonatal factors identified from birth certificates, and 2) validated associations between SIB and developmental, behavioral, medical factors accounting for the above prenatal, perinatal, and neonatal factors.

We included 4343 children from the Autism and Developmental Disabilities Monitoring Network from the 2000, 2006, and 2008 surveillance years. Prenatal, perinatal and neonatal characteristics were obtained from birth certificates. SIB and other potential risk factors were abstracted from children's health or education records. The associations between SIB and various potential risk factors were tested using non-linear mixed models.

Lower maternal educational attainment (adjusted odds-ratio [aOR]: 1.35 [95% confidence interval 1.10–1.67]), prenatal maternal cigarette smoking (1.47 [1.09–1.98]), and electronic fetal monitoring during labor (1.70 [1.02–2.84]) were associated with SIB. In addition, we validated previous associations between SIB and developmental regression, lower IQ, behavioral, sensory and sleep problems, co-occurring developmental and psychiatric diagnoses.

The associations between SIB and maternal smoking, low maternal education attainment may be due to various factors, including low SES and limited access to specialized ASD services. Electronic fetal monitoring may be a marker for unmeasured perinatal complications. Findings reported in this study have implications for better understanding of factors associated with SIB to guide prevention and interventions.