Under Construction : Brain connectivity and fatty acid treatment in developmental disorders

Abstract

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are two of the most commonly diagnosed neurodevelopmental disorders. It is hypothesized that deficits in the development of structural and functional connectivity underlie the psychopathology in ASD and ADHD. Further, interest in non-pharmacological treatment of psychiatric disorders has been increasing. One particular alternative that is currently being investigated is supplementation with omega-3 polyunsaturated fatty acids (PUFA’s). Using various neuroimaging methods, the studies in part I of this thesis tried to unravel the characteristics of the (dis)connected brain from multiple perspectives in both ASD and ADHD. In part II we explored the effects of omega-3 fatty acids on human brain development, and whether dietary supplementation with omega-3 fatty acids proves to be a suitable (augmentation to) therapy for ADHD by means of a double-blind randomized, placebo-controlled trial. We showed ASD is characterized by a heterogeneous pattern of changes in functional connectivity during task and rest. Further, we found with age-related differences in structural connectivity of the Forceps Minor that were related to the pattern of prefrontal gyrification in ASD. Taken together, these findings, combined with current literature, suggest that the complex pattern of increases and decreases in brain connectivity is not sufficiently captured by the current neurobiological models of ASD. This emphasizes the need for the development of more refined neurobiological models that better describe the relation between the symptoms of ASD and the underlying neurobiology. In ADHD, the increased connectivity in prefrontal resting-state networks is in keeping with a pattern of delayed network development, but these differences were present without changes in structural connectivity. Here, longitudinal studies are needed to validate whether these findings indeed fit with the hypothesized developmental delay and to elucidate how the developmental pathways of structural and functional connectivity interact. The studies in part II showed that the effect of omega-3 PUFA’s varies throughout the lifespan. During gestation and early development, omega-3 PUFAs may optimize conditions for adequate development of brain connectivity, whereas during aging omega-3 PUFAs primarily seem to have a neuroprotective effect. Further, there is some evidence to suggest that deficits in the prenatal accrual of omega-3 PUFAs may give rise to various psychiatric disorders, such as schizophrenia, depression or ADHD. However, there is no consistent evidence to date of effects of omega-3 PUFAs on neurobiology of such disorders.

Specifically, our study showed that symptoms of inattention were reduced in children receiving a high dose of omega-3 PUFAs as compared to children receiving placebo. The severity of inattention problems was also related to omega-3 PUFA status as measured in cheek-cell phospholipids. However, no treatment effects were observed on cognitive control, or brain activation. As dopaminergic turnover measured in urine did not seem to be affected either, we took these findings to suggest that the neural mechanism underlying the improvements in attention did not involve dopaminergic cognitive control networks. Nevertheless, these findings do suggest that supplementation with omega-3 PUFAs may be an effective augmentation of pharmacological treatments of ADHD.