Autism and ADHD as opposites based on fly models?
Regular readers of this blog will know my fascination with autism and psychosis as opponents on a continuum theory . I have already been privately speculating that ADHD in childhood may be a risk factor for Psychosis in later adolescence, especially as both are supposed to have underling dopamine abnormalities, so this new study by Brembs et al caught my attention.
Recently I came cross this paper by Bjorn Brembs et al that investigated attention-like processes in mutant fly models that showed memory deficits. They weer aqble to show that despite overt similar olfactory memory deficits, the attention-like processes worked in opposite ways in the two mutant models. In the rutabaga/dunce model, the atention ws hyperfocussed , resembling human autism; while in radish models , attention was flexible and distract-able resembling human ADHD.
It is increasingly apparent that many classical Drosophila learning and memory mutants are also defective in short-term processes relevant to selective attention. Previous studies have shown that short-term memory as well as long-term memory mutants display attention-like defects (van Swinderen, 2007; van Swinderen et al., 2009), and the current study reveals radish mutants to be defective as well, albeit with distinctly different symptoms. The Drosophila mutants dunce1, rutabaga2080, and radish1 share olfactory memory defects but differ conspicuously for short-term processes relevant to visual attention. Whereas the more persistent optomotor behavior of dunce1 and rutabaga2080, both affecting the cAMP-associated pathways (Davis et al., 1995), are reminiscent of the persistent preoccupation of some patients afflicted with autism, the phenotype of radish mutant flies described here is similar to some of the symptoms of patients with ADHD.
They further speculate as o why these two phenotypes may be present and relate it to exploit/explore conundrum.
Attaining the right balance between persistence and flexibility is a crucial feature of adaptive behavior, because it reflects the balance between exploration and exploitation of natural resources. It is tempting to speculate that radish and dunce/rutabaga may constitute the two respective extremes of this balance. Recent work investigating torque behavior of wild-type flies (similar to our shorter experiments here) has shown that, during extended flights, the occurrence of turning maneuvers can be described by a Le´vi distribution (Maye et al., 2007). Such distributions of behavioral output, seen in foraging behavior in many animals, are characteristically long-tailed. This means that animals may occasionally persist with one behavioral choice for unusually long, but most often choices alternate at a more regular, normally distributed rate. The advantage of allowing for occasional long forays into one direction is presumably to chance on a new resource away from the proximal search space. Such behavior has been found to be ecologically advantageous, but mechanisms driving such alternation tendencies have not been documented in the Drosophila brain. One interpretation of our results is that the mushroom body circuits defined by dunce/ rutabaga/radish expression are involved in establishing the balance between persistence and flexibility [i.e., the explore/exploit dilemma (Daw et al., 2006)]. A separate set of results has independently also arrived at a similar conclusion, suggesting that the mushroom bodies could be involved in maintaining a period of behavioral flexibility (i.e., attention-like processes) before a longer-term transition to habit formation or motor learning
To me, this research adds another intriguing possibility to the autism-psychosis dimension, that of ADHD as a childhood phenotype/risk factor for later psychosis.
van Swinderen, B., & Brembs, B. (2010). Attention-Like Deficit and Hyperactivity in a Drosophila Memory Mutant Journal of Neuroscience, 30 (3), 1003-1014 DOI: 10.1523/JNEUROSCI.4516-09.2010
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