Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study

Nina Karolina Mikita, Emily Simonoff, Daniel S. Pine, Robert Nicholas Goodman, Eric Artiges, Tobias Banaschewski, Arun L W Bokde, Christian Buchel, Anna Cattrell, Patricia Conrad, Sylvane Desrivieres, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Andreas Heinz, Bernd Ittermann, Sarah Jurk, Jean-Luc Martinot, Marie-Laure Paillere Martinot, F NeesDimitri Papadopoulos Orfanos, Tomáš Paus, Luis Poustka, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Argyris Stringaris

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Up to 40% of youth with ASD also suffer from anxiety and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2x2 ANOVA (ASD traits: low/high, anxiety symptoms: low/high), controlling for plausible covariates. Additionally, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at two-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters pFWE<.05). BOLD activation patterns in right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth.
Original languageEnglish
JournalTranslational psychiatry
Publication statusAccepted/In press - 20 Apr 2016


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