Serotonergic Modulation of Go/No-Go Executive Function Task In People with Asperger: An fMRI and Acute Tryptophan Depletion Study

Background: One of the triad of impairments characterising Autistic Spectrum Disorder (ASD) is stereotyped, repetitive and obsessional behaviours. It is proposed that these symptoms may be related to executive functions difficulties including inhibitory control set shifting.  Compared to a control group, people with ASD showed increased brain activation when performing a go/no-go  test, a motor inhibition task during a functional Magnetic Resonance (fMRI) experiment.  Impulsiveness is known to be mediated by the neurotransmitter serotonin (5-HT), and the 5-HT system is abnormal in ASD.  The serotonergic system in the brain can be manipulated with the technique of Acute Tryptophan Depletion. (ATD).

Objectives: To study the modulatory role of 5-HT on stereotyped  and repetitive behaviours in ASD.  The hypothesis is that modulation of the serotonergic neurotransmitter system by acute tryptophan depletion would differentially affect brain activity when performing a go/no-go motor inhibition task by people with ASD and controls.

Methods: We studied 14 high-functioning right handed adult male volunteers clinically diagnosed by ICD-10 as having Asperger’s Syndrome and 14 healthy age, gender, handedness and IQ matched controls.  Subjects were tested on two separate occasions using a double-blind, placebo-controlled, crossover designed experiment.  An amino acid drink mixture was consumed on the both test dates after fasting from the previous day. The placebo or sham drink contained tryptophan, the precursor of 5-HT in the brain while the ATD drink did not contain tryptophan leading to the lowering of  brain 5-HT.  Then 4.5 hours post amino acid drink, subjects were scanned in a 1.5 Tesla GE Signa MRI machine measuring Blood Oxygenation Level Dependent (BOLD) signal while performing the go/no-go motor inhibition task.  A 2 drink (sham,  atd) X 2 group (control, asperger) factorial repeated measures ANOVA of the BOLD signal was undertaken to determine brain regions where there was an interaction of 5-HT status and group. 

Results: On the sham day blood tryptophan values were increased and on the ATD day reduced for both groups.  There was no effect on the performance of the go/no-go task based on drink.  There were inteactions of 5-HT status and group in right middle temporal lobe and left hippocampus.

Conclusions: People with Asperger show effects of serotonergic manipulation in the brain regions involved with performing a motorinhibition task and these effects differ from the results in a well-matched control group.