In a recent study published in the journal Autism Researcha group of researchers examined the association between family history of neurodevelopmental disorders (NDD) and neuropsychiatric (NPD) disorders and developmental outcomes in younger siblings (SIBS) of children with autism.
Study: Family history of psychiatric conditions and development of siblings of children with autism. Image credit: Berit Kessler / Shutterstock
Record
Autism spectrum disorder (autism) is a neurodevelopmental condition characterized by social and communication impairments, sensory sensitivities, repetitive behaviors and stereotyped interests. The prevalence of autism in the United States is estimated at 2.78%. Having an autistic relative increases the likelihood of recurrence within the family, with greater genetic similarity correlating with greater likelihood. In addition, families with a history of NDD and NPD disorders, such as intellectual disability, attention deficit hyperactivity disorder (ADHD), anxiety, and depression, also have an increased chance of autism. Further research is needed to better understand the influence of family history on the varied phenotypic outcomes in siblings of children with autism, which could improve early identification and intervention strategies.
About the study
The present study involved 229 children with at least one older sibling diagnosed with autism. Participants, recruited between March 2006 and May 2022 at a median age of 25 months, were included if their sibling had a clinical diagnosis of autism. Exclusion criteria included gestational age less than 34 weeks, sensory disturbances, nonfebrile seizures, or known genetic syndromes. The sample included 64% men and 36% women, who predominantly identified as White (79%). Family history was collected using the Family History Interview (FHI) form, focusing on neurodevelopmental and psychiatric conditions in first-, second-, and third-degree relatives, analyzed in a binary fashion.
Autistic traits were measured using the Autism Diagnostic Observation Schedule-2 (ADOS-2). At the same time, intelligence quotient (IQ) was assessed using the Differential Ability Scale-III (DAS-III) or the Mullen Scales of Early Learning (MSEL) for younger children. Adaptive functioning was assessed using the Vineland Adaptive Behavior Scales (VABS-II). Phenotypic data were collected at the most recent visit, with clinical best estimate (CBE) diagnoses based on comprehensive assessments.
Multivariate linear regression analyzed the association between family history and phenotypic outcomes, controlling for birth year, sex, race, ethnicity, and parental education. Statistical analyzes were performed using R statistical software, version 4.3.1.
Study results
Based on completed assessments, 51 (22%) of the 229 children received a diagnosis of autism, 79 (35%) exhibited broader autism phenotype (BAP) features or other clinically significant concerns, and 99 (43%) had typical results. These ratios are in line with previous reports of developmental outcomes in sibling cohorts, emphasizing the phenotypic heterogeneity in this population. Siblings with and without a diagnosis of autism did not differ significantly in age at intake or phenotypic assessment.
The prevalence of NDD and NPD among siblings was consistent with other reports in families with autism. Speech delay requiring treatment was the most commonly reported NDD (64%), followed by ADHD (41%) and intellectual disability (ID) (11%). Anxiety disorders (44%), depression (43%), bipolar disorder (17%) and schizophrenia (8%) were the most common NPDs.
Family history variables explained 7% and 5% of the variability in ADOS-2 social emotion (SA) and restrictive and repetitive behaviors (RRB) scores, respectively, after controlling for covariates. SA scores were higher in siblings with a family history of anxiety disorders and schizophrenia, whereas RRB scores showed a trend toward higher with a family history of ID.
Family history accounted for 17% and 14% of the variance in verbal and nonverbal IQ scores. Verbal IQ was negatively associated with a family history of intellectual disability (ID) and anxiety disorders and positively associated with a history of depression. Nonverbal IQ showed similar associations, with decreases associated with ID and anxiety disorders and increases associated with depression. Having a relative with ID or an anxiety disorder was associated with lower verbal and nonverbal IQ scores, while a history of depression was associated with higher scores.
Family history variables explained 14% and 10% of the variance in VABS-II Communication and Socialization scores, respectively. Communication scores were negatively associated with family history of ID, anxiety, and bipolar disorders and positively associated with depression. Socialization scores were negatively associated with family histories of anxiety, schizophrenia, and bipolar disorders. A history of depression was associated with higher Communication scores, while a family history of ID, anxiety, and bipolar disorders were associated with lower Communication and Socialization scores.
conclusions
In summary, this study shows, for the first time, that these phenotypic outcomes in SIBS are associated with a family history of anxiety, depression, schizophrenia, bipolar disorders, and ID. While some disorders were associated with lower levels of functioning, depression was associated with more optimal outcomes. After controlling for covariates, family history of NDD and NPD disorders accounted for 5% to 17% of the variance in outcomes, with effect sizes ranging from small to medium.
