27792
Antidepressants Modulate Brain Activation Differently in Autism Compared to Controls
Individuals with autism spectrum disorder (ASD) often suffer from psychiatric comorbidities such as anxiety and depression. Current treatments for these conditions are identical to those in neurotypical populations and include selective serotonin reuptake inhibitors (SSRIs). The effectiveness of SSRIs in ASD is controversial as; 1) limited treatment response and increased adverse events have been reported (Williams et al. 2013), and 2) disruptions in the serotonergic system have been widely described. Furthermore, we demonstrated that reducing serotonin by acute tryptophan depletion normalizes brain function abnormalities in ASD (Daly et al. 2014). Therefore, treatment with an existing drug that reduces serotonin - such as the selective serotonin reuptake enhancer (SSRE) tianeptine - may be more appropriate. Furthermore, it has been suggested that differences in the serotonergic system may underlie altered neurocognitive function in ASD. Hence, investigating the modulating role of serotonergic antidepressants on neurocognitive functions in ASD may help to explain the differences in treatment response, which could lead to better tailored interventions.
Objectives:
To test the effect of the SSRI citalopram and the SSRE tianeptine, on sustained attention and inhibitory networks in ASD.
Methods:
Nineteen right-handed adult males with ASD (diagnosed using the ADI-R and ADOS) and 19 typically developed controls (TD) were included. Pharmacological magnetic resonance imaging (phMRI) was used to compare brain activity during a sustained attention task and a Go/No-Go task under an acute dosage of 20 mg citalopram, 12.5 mg tianeptine and placebo in a randomized, double-blind, crossover procedure. The phMRI data were analyzed using a nonparametric approach (c.f. http://brainmap.it) and significance was defined as p <.05 (corrected for multiple comparisons).
Results:
There were significant interaction effects of BOLD signal response between drug status (placebo, citalopram and tianeptine) and group (TD, ASD) during both the sustained attention and Go/No-Go task. During sustained attention both citalopram and tianeptine significantly downregulated brain activation in the right thalamus in the control group. In contrast, both drugs upregulated brain activation in the right thalamus in individuals with ASD. During response inhibition both citalopram and tianeptine decreased brain activation in the anterior cingulate cortex in the control group whereas both drugs increased brain activation in ASD.
Conclusions:
Our findings support the evidence that antidepressant treatments commonly used in neurotypical populations may not be as ‘translatable’ to individuals with ASD as currently assumed. Thus, pharmacological interventions affecting the serotonergic system need to be tested specifically in the ASD population.