Project ID NS-MH2024_06

ThemeNS-MH

Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Academic Psychiatry, Department of Forensic and Neurodevelopmental ScienceWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Academic Psychiatry, Department of Forensic and Neurodevelopmental ScienceWebsite

The impact of MDMA on prosocial processing in psychopathy: a randomised cross over study using fMRI

Adults with antisocial personality disorder with (ASPD+P) and without (ASPD-P) psychopathy commit the majority of violent crimes in society. Abnormalities of social cognition underpin the dysfunctional interpersonal relations that are the hallmark of these disorders, but effective pharmacological treatments are yet to be developed. Impairments in the processing of frustration, affiliation and reward learning in such men have been demonstrated by our group and others. Our group were the first to show that the social neuropeptide oxytocin can normalize the functional deficits of empathic processing in psychopathy.

This project will explore whether the serotoninergic agent MDMA has the potential to reduce frustration in the absence of a reward, to promote affiliation and to improve social reward learning, and to explore differential effects in the +P/-P groups. In a placebo-controlled, randomized crossover design, violent offenders (men with ASPD+P or ASPD-P) and healthy non-offenders will receive MDMA or placebo and then complete a battery of fMRI tasks assessing behavioural responses to social provocation, co-operation, and social reward learning. The results of this work have the potential to inform the development of treatment approaches in disorders with significant personal and societal impact.

The overarching objectives are: Year 1: Clinical assessment, neuroimaging acquisition and analysis training; systematic review and meta-analysis of serotoninergic abnormalities in violent antisocial behaviours Year 2: RCT neuroimaging data acquisition Year 3: Analysis and write up of dataset

The student will be embedded in Europe’s leading clinical research group in neurodevelopmental disorders, with a committed PhD student cohort, where they will develop cutting edge skills in clinical ‘deep phenotyping’ assessment and in structural and functional neuroimaging analysis.

Representative Publications

Tully J, Sethi A, Griem J, Paloyelis Y, Craig M, Williams S, Murphy D, Blair J, Blackwood N (2023) Oxytocin normalises the implicit processing of fearful faces in psychopathy: a randomised crossover study using fMRI Nature Mental Health 1, 420–427 doi.org/10.1038/s44220-023-00067-3

Tully J, Cross B, Gerrie B, Griem J, Blackwood N, Blair J, McCutcheon R (2023) A systematic review and meta-analysis of brain volume abnormalities in disruptive behaviour disorders, antisocial personality disorder and psychopathy. Nature Mental Health 1, 163–173 doi.org/10.1038/s44220-023-00032-0

Sethi A, O’Brien S, Blair J, Viding E, Mehta M, Ecker C, Blackwood N, Doolan M, Catani M, Scott S, Murphy D, Craig M (2022) Selective amygdala hypoactivity to fear in boys with persistent conduct problems after parent training Biological Psychiatry doi.org/10.1016/j.biopsych.2022.09.031

Leyhausen J, Schäfer T, EU-AIMS LEAP Group; Murphy D, Ecker C. (2023) Differences in Intrinsic Gray-Matter Connectivity and their genomic underpinnings in Autism Spectrum Disorder. Biological Psychiatry. 2023 Jun 20:S0006-3223(23)01363-X. doi: 10.1016/j.biopsych.2023.06.010.

Pretzsch CM, Floris DL, EU-AIMS/AIMS-2-TRIALS Consortium; Murphy DGM, Ecker C. (2023) Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism. Molecular Psychiatry. 2023 Mar 29. doi: 10.1038/s41380-023-02016-z.

Ilioska I, Oldehinkel M, Murphy DGM, Ecker C, Mennes M, Beckmann CF, Fornito A, Buitelaar JK. (2023) Connectome-wide Mega-analysis Reveals Robust Patterns of Atypical Functional Connectivity in Autism. Biological Psychiatry. 2023 Jul 1;94(1):29-39. doi: 10.1016/j.biopsych.2022.12.018.