The results from this study add to a small body of literature demonstrating an association between maternal mood disorders and a higher functioning phenotype of ASD. We found that a lifetime history of maternal BP or DEP each was more strongly associated with having a child with ASP compared to AUT after controlling for relevant maternal and child covariates. The data suggest that this association was stronger for maternal BP than DEP. Furthermore, having a child with ASP versus AUT was more likely if mothers had the first onset of their mood disorder prior to having any children. These findings are consistent with those of DeLong and Dwyer [6
] who found higher proportions of bipolar disorder in the first and second degree relatives of probands with a family history of ASP [6
], and also with those of Cohen and Tsiouris [7
] who found associations between maternal depression and a high functioning ASD phenotype in offspring. Our data extend prior work by examining these associations using an internet-based study design that collected maternal self-report data on community-based clinician diagnoses of maternal mood disorder and child ASD.
Why might maternal mood disorders be associated with a higher functioning phenotype in offspring with ASD? One hypothesis is that psychosocial factors may play a role; mothers of children with ASP may experience a different type of caregiving stress than mothers of children with AUT. For example, children with ASP typically receive their diagnosis later than children with AUT [22
]. It is possible that this prolonged diagnostic odyssey, combined with the baffling mixture of strengths and deficits displayed by these children, results in stress different from that experienced by families of children with a more severe, but less ambiguous, status. In addition, children with ASP have high rates of psychopathology, which can exacerbate caregiver stress [20
] and are also most likely to be educated in typical classrooms where they may face difficult social challenges on a daily basis. However, it is difficult to imagine that mothers of children who are higher functioning experience greater overall stress than mothers of more severely affected children. Moreover, our data as well as the findings of other studies indicate that the likely attribution of maternal mood disorders to psychosocial stress is low because most mothers were diagnosed with a mood disorder prior to the birth of their child [2
]. Therefore, psychosocial stress is unlikely the sole determinant underlying this association.
Alternately, there may be a genetic etiology underlying the association between maternal mood disorders and the ASP, rather than AUT, subtype of ASD. As previously mentioned, Delong [28
] proposed two “taxa” of ASD: one that is higher functioning, associated with comorbid anxiety and mood disorders, and linked to a family history of mood disorder (ASP-related), and another that is lower functioning and not linked to a family history of mood disorder (AUT-related). It is possible that shared genetic susceptibilities may give rise to both mood disorders in the mother and the ASP phenotype in offspring. Current research suggests that different genetic etiologies may give rise to different subtypes of autism [29
]. For example, in a sample of 119 males with ASD, autism severity in terms of aggression, fears, and rituals was modified by the mother's monoamine oxidase A (MAOA) genotype [30
]. There is also evidence of differential heritability for different ASDs and ASD-associated traits, as illustrated by a study of 277 twin pairs where at least one twin had an ASD and in which there was higher psychiatric comorbidity, functioning level, and Asperger syndrome concordance among affected monozygotic versus dizygotic twins [31
]. An alternative genetic explanation for the current findings is that maternal mood disorders may “exert a protective effect on cognitive and adaptive functioning” [7
]. According to this idea, in offspring predisposed to developing an ASD, the presence of a maternal mood disorder exposure modifies expression into ASP rather than AUT. Our finding that onset of mood disorder before having children is associated with having a child with ASP, as opposed to AUT, potentially provides support for either of these hypotheses, both of which merit further investigation.
It is important to note that even mothers of children with AUT had high rates of mood disorder, and that a significant number of all mothers with BP or DEP reported inpatient psychiatric hospitalization, suicidality, and recurrent episodes of depression. Clinicians caring for children with ASD are therefore encouraged to consider screening for mood disorders in the mother and to be ready to offer appropriate treatment resources and referrals.
This study has several unique strengths, most notably its large sample size, which enables research on patterns of disease that may be difficult to appreciate in smaller samples. The large sample size also allows for adjustment of potentially confounding variables such as child gender, age, and maternal education level. An additional strength is that health information was collected via the Internet. Current research supports web-based surveys of medical information as a reliable means of data collection [32
]. This has been demonstrated by a similar registry for a disorder related to autism, Rett syndrome [33
], and in other studies using IAN data [34
]. Advantages of internet-based studies include low cost, decreased response burden, greater ease of participation, access to families from rural areas, and anonymity [35
]. Internet usage is high among individuals of parenting age in the US (79% to 87% in 18 to 54 years old; [37
This study has several limitations. First, ASD and mood disorder diagnoses were based on maternal self-report of a clinician diagnosis rather than an in-clinic assessment conducted as part of the study. However, our research was intentionally designed to examine community-based patterns of disease in children with ASD using a self-report data collection method. IAN data show that this method is reliable and valid for ascertaining community-assigned ASD status in participating children [18
]. An IAN validation study of the maternal mood disorder diagnosis has not been conducted. The current study, however, applied stringent self-report criteria by only including mothers who reported a diagnosis of BP or DEP made by a medical or mental health professional and eliminated the 25% of mothers reporting a less well-characterized mood disorder (e.g., self-diagnosed, treated but not formally diagnosed). Some diagnostic misclassifications may have occurred, but these are likely to be overcome by the study's large sample size. Another point to note is that the intent of this study was not to approximate a generalizable population prevalence of actual maternal mood disorders in families of children with ASD, but to determine relative frequencies of illness within the IAN population and examine associations with child phenotype.
Our sample of families may not reflect all US households. The mothers in our study were primarily white, non-Hispanic, highly educated, and over the age of 30 years. However, this demographic profile is similar to that of subjects in other online and clinic-based studies [38
], and there is evidence that web-based samples may actually be more representative of the general population than samples in center-based studies [32
]. Further, although there is a risk of self-selection bias, with affected mothers more likely to complete a maternal mood disorder questionnaire, our findings are based on between-group comparisons, which are largely resistant to this type of selection bias. In addition, when examining frequency of self-reported BP or DEP on a general medical history survey, we found no difference in responses between MatMoodQ responders and nonresponders. In other words, those who had earlier reported a history of BP or DEP were no more likely to take the MatMoodQ than those who had not.