title: Parallel changes in serum proteins and diffusion tensor imaging in methamphetamine-associated psychosis.
abstract: Methamphetamine-associated psychosis (MAP) involves widespread neurocognitive and molecular deficits, however accurate diagnosis remains challenging. Integrating relationships between biological markers, brain imaging and clinical parameters may provide an improved mechanistic understanding of MAP, that could in turn drive the development of better diagnostics and treatment approaches. We applied selected reaction monitoring (SRM)-based proteomics, profiling 43 proteins in serum previously implicated in the etiology of major psychiatric disorders, and integrated these data with diffusion tensor imaging (DTI) and psychometric measurements from patients diagnosed with MAP (N = 12), methamphetamine dependence without psychosis (MA; N = 14) and healthy controls (N = 16). Protein analysis identified changes in APOC2 and APOH, which differed significantly in MAP compared to MA and controls. DTI analysis indicated widespread increases in mean diffusivity and radial diffusivity delineating extensive loss of white matter integrity and axon demyelination in MAP. Upon integration, several co-linear relationships between serum proteins and DTI measures reported in healthy controls were disrupted in MA and MAP groups; these involved areas of the brain critical for memory and social emotional processing. These findings suggest that serum proteomics and DTI are sensitive measures for detecting pathophysiological changes in MAP and describe a potential diagnostic fingerprint of the disorder.
authors.affiliation: Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Breen
authors.affiliation: Department of Psychiatry and Mental Health, and MRC Unit on Anxiety &Stress Disorders, University of Cape Town, South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: Uhlmann
authors.affiliation: Institute of Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sureyya
authors.initials: S
authors.lastname: Ozcan
authors.affiliation: Institute of Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Man
authors.initials: M
authors.lastname: Chan
authors.affiliation: Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.affiliation: Institute of Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
authors.affiliation: Department of Psychiatry and Mental Health, and MRC Unit on Anxiety &Stress Disorders, University of Cape Town, South Africa.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000097:blood / Q000000981:diagnostic imaging*; D001798:Blood Proteins / Q000032:analysis*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods; D011618:Psychotic Disorders / Q000097:blood / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D020543:Proteome