Lay Abstract

Serotonin Hypothesis of Autism: Implications for Selective Serotonin Reuptake Inhibitor Use during Pregnancy

Rebecca A. Harrington, Li-Ching Lee, Rosa M. Crum, Andrew W. Zimmerman, and Irva Hertz-Picciotto


Serotonin is a substance found throughout the brain and body of interest in autism. This is due to repeated findings of elevated serotonin levels in the blood of approximately one third of children with autism, leading some to believe that problems with the serotonin system may explain the development of autism in some cases. Because serotonin is critical in early brain development, concerns have arisen regarding prenatal exposure to factors that influence serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs). This review examines evidence regarding the serotonin system and autism spectrum disorders (ASD), as well as what the literature has reported on the developmental effects of prenatal SSRI exposure. Possible ways in which SSRIs could affect the fetus during pregnancy and clinical implications are also discussed. The majority of studies conducted in infants and children suggest prenatal exposure to SSRIs does not affect neurodevelopment, but limitations in these studies argue for further research. The only published study on prenatal SSRI exposure and ASD found an increased risk with exposure to SSRIs, especially during the first trimester. Obstacles that will be faced in future research are separating the effects of SSRIs from that of maternal depression and assembling a study large enough to adequately address the question. Whether serotonin is an etiologic factor in ASD, and what it points to as a marker in terms of subgrouping, remains unclear. Understanding how the development of ASD is affected by prenatal factors that influence serotonin levels, such as SSRIs, could identify modifiable targets for prevention. © 2013 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2013, 6: 149–168. DOI: 10.1002/aur.1288

Behavior and Sleep Problems in Children With a Family History of Autism

Amy Jo Schwichtenberg, Gregory S. Young, Ted Hutman, Ana-Maria Iosif, Marian Sigman, Sally J. Rogers, and Sally Ozonoff


The present study explores behavioral and sleep problems in preschool-age siblings of children with autism spectrum disorders (ASD). This study focuses on behavior problems that are common in children with ASD, such as anxiety, inattention, aggression, and sleep problems. Siblings were recruited from families with at least one older child with ASD (n = 104) or families with no history of ASD (n = 76). As part of a larger study, children completed a standardized developmental assessment and the Autism Diagnostic Observation Schedule during a laboratory visit at 36 months of age. Parent reports of child behavior problems and autism symptoms/features were also collected at this time. This study focuses on developmental concerns outside of ASD; therefore, only siblings who did not develop an ASD were included in analyses. Statistical analyses revealed that children with a family history of ASD were more likely to have elevated behavior problems in a few areas (anxiety/depression, aggression). For both groups of children, sleep problems were associated with elevated behavior problems in each of the areas assessed (reactivity, anxiety, somatic complaints, withdrawal, attention, and aggression). These findings support close monitoring of children with a family history of ASD for both behavioral and sleep issues. © 2013 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2013, 6: 169–176. DOI: 10.1002/aur.1278

Eye Movement Difficulties in Autism Spectrum Disorder: Implications for Implicit Contextual Learning

Anastasia Kourkoulou, Gustav Kuhn, John M. Findlay, and Susan R. Leekam


Individuals with an autism spectrum disorder (ASD) have atypical visual attention patterns. In some tasks, their ability to visually search for an object may be superior. However, in one type of visual search task that involves processing of context, they tend to respond more slowly compared with a group of typically developing (TD) individuals. In the present study, we studied eye movements during this context based task in order to understand why search is slower. We found that individuals with ASD fixated on the display as many times as TD individuals. This suggests that they viewed the same number of items. Therefore, slower visual search could not have been due to a greater number of changes in the spatial focus of attention. Instead, slower search in ASD stemmed from a slowness to initiate an eye movement, as well as longer fixation durations. These findings are often associated with slower temporal processing of information. It is concluded that the slower search in ASD, as documented in the contextual cueing task, is not due to difficulties in the spatial shifting of attention but due to temporal delays in preparing eye movements and in processing the items of the display. © 2013 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2013, 6: 177–189. DOI: 10.1002/aur.1274

Functional Assays of Local Connectivity in the Somatosensory Cortex of Individuals with Autism

Mehmet Akif Coskun, Katherine A. Loveland, Deborah A. Pearson, Andrew C. Papanicolaou, and Bhavin R. Sheth


It is widely accepted that the brains of individuals with autism spectrum disorder (ASD) are wired differently from those without. The precise manner in which brain wiring differs between individuals with ASD from neurotypicals remains unresolved, however. Measuring physiological response to sensory stimulation using neuroimaging sheds light on brain connectivity “in action.” Touch is an important sensory modality and critical for normal human development. Differences in tactile perception and sensitivity of individuals with ASD from control have been demonstrated, and clear relationships between brain connectivity and physiological function have been established. Thus, studying the brain's response to touch should help illuminate how the brains of individuals with ASD are wired. In particular, the response of neurons that are most active to the tactile stimulation of a finger to that of a neighboring finger assays the strength of local connections in cortex. Local overconnectivity, a leading theoretical account of brain function in autism, predicts stronger response in autism. To investigate this, we imaged the somatosensory cortex of individuals with and without ASD, while the thumb and index finger were individually stimulated with gentle pressure, and computed the response of neurons best responsive to the thumb in response to stimulation of the index finger and vice versa. Our results do not support local overconnectivity but rather local underconnectivity in autism. Local underconnectivity is in line with the idea of an imbalance in the levels of local excitation and inhibition in the brains of individuals with autism. © 2013 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2013, 6: 190–200. DOI: 10.1002/aur.1276

Is There a Bidirectional Relationship Between Maternal Well-Being and Child Behavior Problems in Autism Spectrum Disorders? Longitudinal Analysis of a Population-Defined Sample of Young Children

Vasiliki Totsika, Richard P. Hastings, Eric Emerson, Gillian A. Lancaster, Damon M. Berridge, and Dimitrios Vagenas


The behavior problems of children with autism have been associated with decreased well-being in their mothers. Children's behavior and mothers' well-being are thought to affect each other. With this study, we wanted to find out whether they affect each other in the long term. We identified 132 5-year-old children with an autism spectrum disorder (ASD), among 15 246 5-year-olds selected throughout the United Kingdom. Working backwards, we looked at their problem behaviors at the age of 5 and 3, and their difficult temperament as 9-month-old babies. We examined how these are associated with mothers' psychological distress, life satisfaction, and physical health problems over time. Each indicator of maternal well-being (distress, life satisfaction, and physical health limitations) had a long-term effect on children's behavior problems. However, in no case did children's behavior problems have an impact on their mothers' well-being through the first 5 years of life. This pattern of results was systematic for each type of maternal well-being. We concluded that behavior problems in young children with ASD do not have an adverse effect on maternal well-being through the first 5 years of life. However, mothers' well-being can affect the development of later behavior problems in children. For this, improving well-being and increasing resilience in mothers offers perhaps another way for improving children's behavior and for strengthening the whole family system. © 2013 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2013, 6: 201–211. DOI: 10.1002/aur.1279

Letting a Typical Mouse Judge Whether Mouse Social Interactions Are Atypical

Charisma R. Shah, Carl Gunnar Forsberg, Jing-Qiong Kang, and Jeremy Veenstra-VanderWeele


Diagnosis of an autism spectrum disorder (ASD) requires a qualitative assessment of social aptitude: one person judging whether another person interacts in a “typical” way. Quantitative or computerized assessment of social aptitude cannot substitute for this subjective judgment. We hypothesized that mice could be used to make a similar judgment if they prefer “typical” over “atypical” social interactions with mouse models relevant to ASD. We used typical C57BL/6 (B6) mice as “judges” and evaluated their preference for a chamber containing a “typical” or an “atypical” mouse. For our atypical mice, we chose two strains with well-documented social phenotypes, as well as a mutant line with abnormal social behavior and seizures. Overall, we observed a characteristic pattern of behavior over the course of 30 min, with the judges preferring the typical mouse chamber to the atypical mouse chamber during the last 10 min of the test. When we evaluated the individual stimulus pairings, two of the three showed a similar pattern as the overall results, and the other stimulus comparison showed a trend for a preference for the typical mouse chamber across the entire test. We repeated the experiments using the 129S6 strain of typical mice as judges and found a much less strong preference pattern across time. These data suggest that a characteristic pattern of exploration in B6 mice can distinguish some socially atypical animals from controls. © 2013 INSAR/Wiley Periodicals, Inc.

Article citation: Autism Res 2013, 6: 212–220. DOI: 10.1002/aur.1280