Platelet serotonin, a possible marker for familial autism.
ABSTRACT Serotonin (5HT) levels in platelet-rich plasma were measured in 5 autistic subjects who had siblings with either autism or pervasive developmental disorder (PDD), 23 autistic subjects without affected siblings, and 10 normal controls. The 5HT levels of autistic subjects with affected siblings were significantly higher than probands without affected siblings, and autistic subjects without affected siblings had 5HT levels significantly higher than controls. Differences in 5HT levels remained significant after adjustment for sex, age, and IQ. These results suggest that 5HT level in autistic subjects may be associated with genetic liability to autism.
- SourceAvailable from: Eileen Daly[Show abstract] [Hide abstract]
ABSTRACT: It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target.Brain 07/2014; 137. DOI:10.1093/brain/awu178 · 10.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share brain function abnormalities during cognitive flexibility. Serotonin is involved in both disorders, and selective serotonin reuptake inhibitors (SSRIs) can modulate cognitive flexibility and improve behavior in both disorders. Thus, this study investigates shared and disorder-specific brain dysfunctions in these 2 disorders during reward reversal, and the acute effects of an SSRI on these. Age-matched boys with ADHD (15), ASD (18), and controls (21) were compared with functional magnetic resonance imaging (fMRI) during a reversal task. Patients were scanned twice, under either an acute dose of Fluoxetine or placebo in a double-blind, placebo-controlled randomized design. Repeated-measures analyses within patients assessed drug effects. Patients under each drug condition were compared with controls to assess normalization effects. fMRI data showed that, under placebo, ASD boys underactivated medial prefrontal cortex (mPFC), compared with control and ADHD boys. Both patient groups shared decreased precuneus activation. Under Fluoxetine, mPFC activation was up-regulated and normalized in ASD boys relative to controls, but down-regulated in ADHD boys relative to placebo, which was concomitant with worse task performance in ADHD. Fluoxetine therefore has inverse effects on mPFC activation in ASD and ADHD during reversal learning, suggesting dissociated underlying serotonin abnormalities.Cerebral Cortex 01/2014; 25(7). DOI:10.1093/cercor/bht365 · 8.31 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Autism spectrum disorders (ASD) are important neuropsychiatric disorders, currently estimated to affect approximately 1% of children, with considerable emotional and financial costs. Significant collaborative effort has been made over the last 15 years in an attempt to unravel the genetic mechanisms underlying these conditions. This has led to important discoveries, both of the roles of specific genes, as well as larger scale chromosomal copy number changes. Here, we summarize some of the latest genetic findings in the field of ASD and attempt to link them with the results of pathophysiological studies to provide an overall picture of at least one of the mechanisms by which ASD may develop.EMBO Molecular Medicine 08/2011; 3(8):438-50. DOI:10.1002/emmm.201100157 · 8.25 Impact Factor