All Group Leaders 

Brain development and Psychopharmacology in Neurodevelopmental disorders

Grainne McAlonan

Grainne McAlonan

Professor of Translational Neuroscience

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Overview

Grainne McAlonan leads the Child and Neurodevelopmental Disorders Theme of the NIHR-Maudsley Biomedical Research Centre. She is also a lead researcher in the adult experimental medicine and the perinatal brain imaging studies in AIMS-2-TRIALS (the world’s largest autism grant).  Her research work is informed by the people she sees in the National Autism and ADHD Service for Adults in South London and Maudsley NHS Foundation Trust.

The challenge with neurodevelopmental conditions such as autism is their complexity. By the time a person is diagnosed (even if in childhood), they will have lived with the direct consequences of autism and experienced secondary or compensatory influences which shape the brain. This complicates research. Our group recognises that complexity is built on more fundamental building blocks starting from early in life. 

Using MRI, we’ve been finding that the structure and activity of brain sensory systems of babies who go on to have features associated with autism, are already developing differently at birth.

Using EEG, we’ve been finding that the autistic brain is over responsive to sounds and processes visual information differently. Specifically, in autism, repeated irrelevant sounds are not ignored; and ‘background’ interference that should reduce the brain’s response to visual stimuli, doesn’t. Thus, there are sensory ‘suppression’ differences in the autistic brain. The extent of these sensory processing differences predicts (and is likely upstream of) more complex behaviours and autistic traits.

Using single doses of drugs with a known mechanism of action, we are now investigating how brain chemical systems influence sensory processing. For example, we’ve discovered that arbaclofen – a drug which acts on the brain’s inhibitory GABA system – boosts suppression of sensory responses in the autistic brain. This drug is now in a clinical trial across Europe.

Selected publications

Huang Q, Pereira AC, Velthuis H, Wong NML, Ellis CL, Ponteduro FM, Dimitrov M, Kowalewski L, Lythgoe DJ, Rotaru D, Edden RAE, Leonard A, Ivin G, Ahmad J, Pretzsch CM, Daly E, Murphy DGM, McAlonan GM (2022) GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder. Sci Transl Med 14: eabg7859

Ciarrusta J, O'Muircheartaigh J, Dimitrova R, Batalle D, Cordero-Grande L, Price A, Hughes E, Steinweg JK, Kangas J, Perry E, Javed A, Stoencheva V, Akolekar R, Victor S, Hajnal J, Murphy D, Edwards D, Arichi T, McAlonan G (2019) Social Brain Functional Maturation in Newborn Infants With and Without a Family History of Autism Spectrum Disorder. JAMA Netw Open 2: e191868

Pretzsch CM, Freyberg J, Voinescu B, Lythgoe D, Horder J, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Edden RAE, Williams S, Murphy DGM, Daly E, McAlonan GM (2019) Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder. Neuropsychopharmacology