Parental History of Mood/Affective Disorders and Regression among Children with ASD: Results from AGRE Families

Background: There is an abundance of literature supporting a preponderance of mood and affective disorders in the family histories of children with autism spectrum disorders (ASD; e.g., Bolton et al., 1998; Delong & Dwyer, 1988; Ghaziuddin & Greden, 1998; Lainhart & Folstein, 1994; Smalley et al., 1995; Zapella, 1996). However, it is not known whether a relationship exists between familial history of mood/affective disorders and regression in children with ASD. Some children with a history of developmental regression (e.g., those with cerebral folate deficiency, a subset of children with autism) have demonstrated abnormalities in folate metabolism that are corrected with folinic acid supplementation (James et al., 2004; Moretti et al., 2005). Interestingly, several reports also note (a) reduced folate levels among individuals with mood/affective disorders and (b) that folate supplementation in conjunction with pharmacological agents is superior to drug treatment alone in terms of facilitating clinical improvements in these individuals (e.g., Coppen & Bolander-Gouaille, 2005; Morris, Trivedi, & Rush, 2008). Thus, it seems plausible that parental history of mood/affective disorders could be a risk factor for developmental regression in ASD via an inherited disposition for abnormal folate metabolism.

Objectives: To examine (a) whether regression among children with ASD is more often associated with a parental history of mood/affective disorders and (b) whether children with the regressive endophenotype are different from children with autism who have not experienced regression in terms of level of functioning (i.e., IQ and adaptive behaviors).

Methods: Data were ascertained on the 361 families in the Autism Genetic Resource Exchange (AGRE) collection on whom parental medical history data is available. Phenotypic and demographic data of interest were downloaded from the AGRE website and imported into a SAS database. The proportion of parents with a mood/affective disorder was calculated using information in the medical history form. Loss (regression) items from the two different versions of the Autism Diagnostic Interview-Revised (ADI-R) were combined so that comparable/identical items were represented as one variable within the dataset.

Results: Preliminary analyses reveal a mood/affective disorder in one or both parents among 47.4% of this sample. Of the 748 children born to these parents, 35.0% experienced some form of regression, with 25.5% and 28.9% experiencing language loss or some other skill loss (i.e., social, play, self-help, motor, hand use), respectively. One-way ANOVA’s indicate significant differences in level of functioning between children with ASD who have and have not regressed per the Peabody Picture Vocabulary Test-III, the Ravens Colored Progressive Matrices, and the Vineland Adaptive Behavior Scales. Chi-square and logistic regression analyses will be used to determine whether parental history of mood/affective disorder predicts a history of regression in these children.

Conclusions: Results are congruent with prior research on level of functioning among children with ASD who have/have not regressed. Next-step analyses will reveal whether parental history of mood/affective disorder is associated with regression in children with ASD and, if so, whether it increases or decreases risk for regression.