- Overview
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Our research (which depends critically on the collaborative contributions of many laboratory co-investigators and other clinician-scientists) aims to identify the major genetic alterations that confer risk of severe, treatment-resistant psychosis and co-morbid neurodevelopmental and psychiatric disorders, by identifying rare or novel, mechanistically potent genetic alterations involving brain-expressed genes, with the aim of using this information to develop precision medicine (i.e., individualized treatment based on a mechanistic understanding of disease causation). Deep clinical phenotyping, clinical chromosomal microarrays, long read whole genome and short read RNA sequencing, biochemical and immunological profiling, many bioinformatic tools, and intensive genotype-phenotype correlation are utilized to detect, filter, and prioritize rare genetic variants and deliver actionable genetic and pharmacogenomic results through psychiatric genetic counselling. We collaborate with model organism and synaptic function researchers to try to identify tractable treatment targets.
- Publications
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Medical Multimorbidity in Patients with Treatment-Resistant Psychosis and Rare Copy Number Variants: A Retrospective Case Series of 24 Patients
Tyler E. Dietterich and Rose Mary Xavier and Maya L. Lichtenstein and Matthew K. Harner and Lisa Bruno and Robert Stowe and Martilias Farrell and Rita A. Shaughnessy and Jonathan S. Berg and Patrick F. Sullivan and Richard C. Josiassen
DOI: 10.1101/2025.05.13.25325400
05/2025T74. HIGH YIELD OF DEEP PHENOTYPING AND LONG READ WHOLE GENOME SEQUENCING IN TREATMENT-RESISTANT PSYCHOSIS
European Neuropsychopharmacology
Gagan Singh and Indhu-Shree Rajan-Babu and Prescilla Carrion and William Rowell and Sanja Rogic and Mohadeseh Gharib Pour and Mike Guron and Julie MacIsaac and Agata Minor and Monica Hrynchak and Randall White and William Honer and Patrick Sullivan and Paul Pavlidis and Robert Stowe
DOI: 10.1016/j.euroneuro.2024.08.384
10/2024The curious absence of psychosis in GRIN1-related neurodevelopmental disorder
European Archives of Psychiatry and Clinical Neuroscience
Colijn, M.A. and Stowe, R.M.
DOI: 10.1007/s00406-024-01796-x
2024SETD1A variant-associated psychosis: A systematic review of the clinical literature and description of two new cases
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Colijn, M.A. and Carrion, P. and Poirier-Morency, G. and Rogic, S. and Torres, I. and Menon, M. and Lisonek, M. and Cook, C. and DeGraaf, A. and Thammaiah, S.P. and Neelakant, H. and Willaeys, V. and Leonova, O. and White, R.F. and Yip, S. and Mungall, A.J. and MacLeod, P.M. and Gibson, W.T. and Sullivan, P.F. and Honer, W.G. and Pavlidis, P. and Stowe, R.M.
DOI: 10.1016/j.pnpbp.2023.110888
2024Virtual twins for model-informed precision dosing of clozapine in patients with treatment-resistant schizophrenia
CPT: Pharmacometrics and Systems Pharmacology
Mostafa, S. and Rafizadeh, R. and Polasek, T.M. and Bousman, C.A. and Rostami-Hodjegan, A. and Stowe, R. and Carrion, P. and Sheffield, L.J. and Kirkpatrick, C.M.J.
DOI: 10.1002/psp4.13093
2024ASSESSING THE UTILITY OF PHARMACOGENETIC TESTING IN A COHORT WITH TREATMENT-RESISTANT SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER
European Neuropsychopharmacology
Natasha Verzosa and Hilary Williams and Reza Rafizadeh and Ankita Narang and Prescilla Carrion and Ric Procyshyn and Randall White and Guillaume Poirier-Morency and Sanja Rogic and Andrew Mungall and Patrick Sullivan and William Honer and Paul Pavlidis and Robert Stowe and Chad Bousman
DOI: 10.1016/j.euroneuro.2022.07.282
10/2022Subjective cognitive functioning, depressive symptoms, and objective cognitive functioning in people with treatment-resistant psychosis
Cognitive Neuropsychiatry
Zumrawi, D. and Glazier, B.L. and Leonova, O. and Menon, M. and Procyshyn, R. and White, R. and Stowe, R. and Honer, W.G. and Torres, I.J.
DOI: 10.1080/13546805.2022.2108389
2022Progressive neurocognitive decline in schizophrenia: A diagnostic dilemma for clinicians
Schizophrenia Research
Colijn, M.A. and Torres, I.J. and Menon, M. and Howard, A. and Honer, W.G. and Stowe, R.M.
DOI: 10.1016/j.schres.2022.01.027
2022A 1p31.3 deletion encompassing the nuclear factor 1A gene presenting as possible temporal lobe epilepsy in association with schizoaffective disorder
Neurocase
Colijn, M.A. and Hrynchak, M. and Hrazdil, C.T. and Willaeys, V. and White, R.F. and Stowe, R.M.
DOI: 10.1080/13554794.2022.2132869
2022TU71. SIGNIFICANT INCIDENCE OF RARE CHROMOSOMAL AND GENOMIC SEQUENCE VARIANTS IN HIGHLY TREATMENT-RESISTANT SCHIZOPHRENIA AND SCHIZOAFFECTIVE DISORDER
European Neuropsychopharmacology
Robert Stowe and Guillaume Poirier-Morency and Sanja Rogic and Michelle Lisonek and Jessica Jun and Adrienne Elbert and Kennedy Borle and Courtney Cook and Olga Leonova and Prescilla Carrion and Chad Bousman and Monica Hrynchak and William Honer and Patrick Sullivan and Paul Pavlidis
DOI: 10.1016/j.euroneuro.2021.08.073
10/2021Look Again: Mental Illness Re-examined
BC Schizophrenia Society
Aldridge, F., Cook, C., & Stowe, R. (2021, September 2021). In Schizophrenia: Nature vs. Nuture. F. Aldridge. https://www.bcss.org/lookagain/schizophrenia-nature-vs-nurture/
09/2021Whole-genome sequencing analysis of clozapine-induced myocarditis
medRxiv
Narang, A. and Lacaze, P. and Ronaldson, K.J. and McNeil, J.J. and Jayaram, M. and Thomas, N. and Sellmer, R. and Crockford, D. and Stowe, R. and Greenway, S.C. and Pantelis, C. and Bousman, C.A.
DOI: 10.1101/2021.07.26.21261157
2021Review and Consensus on Pharmacogenomic Testing in Psychiatry
Pharmacopsychiatry
Bousman, C.A. and Bengesser, S.A. and Aitchison, K.J. and Amare, A.T. and Aschauer, H. and Baune, B.T. and Asl, B.B. and Bishop, J.R. and Burmeister, M. and Chaumette, B. and Chen, L.-S. and Cordner, Z.A. and Deckert, J. and Degenhardt, F. and Delisi, L.E. and Folkersen, L. and Kennedy, J.L. and Klein, T.E. and McClay, J.L. and McMahon, F.J. and Musil, R. and Saccone, N.L. and Sangkuhl, K. and Stowe, R.M. and Tan, E.-C. and Tiwari, A.K. and Zai, C.C. and Zai, G. and Zhang, J. and Gaedigk, A. and Müller, D.J.
DOI: 10.1055/a-1288-1061
2021First Whole Transcriptome RNAseq on CHD8 Haploinsufficient Patient and Meta-Analyses Across Cellular Models Uncovers Likely Key Pathophysiological Target Genes
Cureus
Heba Yasin and Robert Stowe and Chi Kin Wong and Puthen Veettil Jithesh and Farah R Zahir
DOI: 10.7759/cureus.11571
11/2020Treatment-resistant psychotic symptoms and early-onset dementia: A case report of the 3q29 deletion syndrome
Schizophrenia Research
Matthew K. Harner and Maya Lichtenstein and Martilias Farrell and Tyler E. Dietterich and Dawn M. Filmyer and Lisa M. Bruno and Tamara F. Biondi and James J. Crowley and Gabriel L{\'{a}}zaro-Mu{\~{n}}oz and Robert Stowe and Rita A. Shaughnessy and Jonathan S. Berg and Jin Szatkiewicz and Patrick F. Sullivan and Richard C. Josiassen}, title = {Treatment-resistant psychotic symptoms and early-onset dementia: A case report of the 3q29 deletion syndrome}, journal = {Schizophrenia Research
DOI: 10.1016/j.schres.2020.08.012
09/2020Clinical and biochemical footprints of inherited metabolic diseases. III. Psychiatric presentations
Molecular Genetics and Metabolism
Horvath, G.A. and Stowe, R.M. and Ferreira, C.R. and Blau, N.
DOI: 10.1016/j.ymgme.2020.02.007
2020Preliminary examination of the validity of the NIH toolbox cognition battery in treatment-resistant psychosis
Clinical Neuropsychologist
Cassetta, B.D. and Menon, M. and Carrion, P.B. and Pearce, H. and DeGraaf, A. and Leonova, O. and White, R.F. and Stowe, R.M. and Honer, W.G. and Woodward, T.S. and Torres, I.J.
DOI: 10.1080/13854046.2019.1694072
2020F104CHROMOSOMAL MICROARRAYS IMPLICATE GENES REGULATING DENDRITOGENESIS – POTENTIAL IMPLICATIONS FOR PRECISION MEDICINE IN BIPOLAR DISORDER AND SCHIZOPHRENIA
European Neuropsychopharmacology
Robert Stowe and Pedram Laghaei and Prescilla Carrion and Agata Minor and Christine Tyson and Ashley DeGraaf and William Honer and Patrick MacLeod and Harish Neelekant and Randall White and Monica Hrynchak
DOI: 10.1016/j.euroneuro.2018.08.184
2019A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8
Journal of Human Genetics
Yasin, H. and Gibson, W.T. and Langlois, S. and Stowe, R.M. and Tsang, E.S. and Lee, L. and Poon, J. and Tran, G. and Tyson, C. and Wong, C.K. and Marra, M.A. and Friedman, J.M. and Zahir, F.R.
DOI: 10.1038/s10038-019-0561-0
2019SA115THE UBC MAGERS STUDY OF SEVERELY TREATMENT-RESISTANT PSYCHOSIS: CHROMOSOMAL MICROARRAY FINDINGS IN THE FIRST 25 CASES
European Neuropsychopharmacology
Robert Stowe and Monica Hrynchak and Agata Minor and Christine Tyson and Prescilla Carrion and Ashley DeGraaf and Pedram Laghaei and Olga Leonova and Mahesh Menon and Ivan Torres and Veerle Willaeys and Randall White and Clara Westwell-Roper and Clare Beasley and William Honer
DOI: 10.1016/j.euroneuro.2018.08.337
2019Developmental delay, treatment-resistant psychosis, and early-onset dementia in a man with 22q11 deletion syndrome and huntington's disease
American Journal of Psychiatry
Farrell, M. and Lichtenstein, M. and Crowley, J.J. and Filmyer, D.M. and Lázaro-Muñoz, G. and Shaughnessy, R.A. and Mackenzie, I.R. and Hirsch-Reinshagen, V. and Stowe, R. and Evans, J.P. and Berg, J.S. and Szatkiewicz, J. and Josiassen, R.C. and Sullivan, P.F.
DOI: 10.1176/appi.ajp.2017.17060638
2018Liver transplant can resolve severe neuropsychiatric manifestations of wilson disease: A case report
Experimental and Clinical Transplantation
Walker, G. and Hussaini, T. and Stowe, R. and Cresswell, S. and Yoshida, E.M.
DOI: 10.6002/ect.2016.0053
2018Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy
Journal of the Neurological Sciences
Horvath, G.A. and Meisner, L. and Selby, K. and Stowe, R. and Carleton, B.
DOI: 10.1016/j.jns.2017.04.047
2017Left hemispatial neglect
Casebook of Neuropsychiatry
2013Dementia syndrome of depression
Casebook of Neuropsychiatry
2013Secondary obsessive-compulsive disorder associated with pallidal lesions
Casebook of Neuropsychiatry
2013Psychosis and cognitive impairment in an adolescent
Casebook of Neuropsychiatry
2013Knife in the Head: German social realism meets Cinema Verité
Senses of Cinema [online journal]
2011A case of persistent visual hallucinations of faces following LSD abuse: A functional Magnetic Resonance Imaging study
Neurocase
Iaria, G. and Fox, C.J. and Scheel, M. and Stowe, R.M. and Barton, J.J.S.
DOI: 10.1080/13554790903329141
2010Serious neurological complications of valproate therapy
BC Mental Health & Addiction Services Psychopharmacology Newsletter
2007Classification images of two right hemisphere patients: A window into the attentional mechanisms of spatial neglect
Brain Research
Shimozaki, S. and Kingstone, A. and Olk, B. and Stowe, R. and Eckstein, M.
DOI: 10.1016/j.brainres.2006.01.033
2006Neuropsichiatria I disturbi del comportamento tra neurologia e psichiatria
Masson
DOI: 10.1007/s10072-004-0359-4
12/2004Neuropsichiatria dei disturbi psicotici
Neuropsichiatria: I disturbi del comportamento tra neurologia e psichiatria, 2nd ed
2004Principi generali di valutazione e diagnosi Neuropsichiatria
Neuropsichiatria: I disturbi del comportamento tra neurologia e psichiatria, 2nd ed.
2004Neuropsichiatria dei disturbi d’ansia
Neuropsichiatria: I disturbi del comportamento tra neurologia e psichiatria, 2nd ed.
2004Alterazioni della personalità associate a lesioni cerebrali
Neuropsichiatria: I disturbi del comportamento tra neurologia e psichiatria, 2nd ed.
2004Funzioni neuropsicologiche ed esame dello stato mentale
Neuropsichiatria: I disturbi del comportamento tra neurologia e psichiatria, 2nd ed.
2004Current concepts of the pathophysiology of catatonia
Canadian Psychiatric Association Bulletin
Stowe, R. M. (2002). Current concepts of the pathophysiology of catatonia. Canadian Psychiatric Association Bulletin, 34(1), 22-24.
02/2002Post-traumatic stress disorder
Encyclopedia of the Life Sciences
2002Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias
Neurology
DOI: 10.1212/wnl.53.6.1292
10/1999I disturbi del comportamento tra neurologia e psichiatria. Basi neurobiologiche e sindromi cliniche [The neurology and psychiatry of behavioral disorders: Neurobiological basis and clinical syndromes]
Italian Journal of Neurological Sciences
Blundo, C. and Stowe, R.
1999Psychosis as a presentation of physical disease in adolescence: a case of Niemann-Pick disease, type C.
Developmental medicine and child neurology
PubMed: 9489503
02/1998Poststroke depression and anxiety: Different assessment methods result in variations in incidence and severity estimates
Journal of Clinical and Experimental Neuropsychology
Schramke, C.J. and Stowe, R.M. and Ratcliff, G. and Goldstein, G. and Condray, R.
DOI: 10.1076/jcen.20.5.723.1117
1998Neuropsichiatria dell’aggressività
I disturbi del comportamento tra neurologia e psichiatria: basi neurobiologiche e sindromi cliniche
1998Assessment Methods in Behavioral Neurology and Neuropsychiatry
Neuropsychology
DOI: 10.1007/978-1-4899-1950-2_20
1998Psychosis as a presentation of physical disease in adolescence: A case of Niemann-Pick disease, type C
Developmental Medicine and Child Neurology
Campo, J.V. and Stowe, R. and Slomka, G. and Byler, D. and Gracious, B.
DOI: 10.1111/j.1469-8749.1998.tb15374.x
1998Principi di valutazione dei disturbi neuropsicologici e neuropsichiatrici
I disturbi del comportamento tra neurologia e psichiatria: basi neurobiologiche e sindromi cliniche
1998Neuropsichiatria dei disturbi d'ansia
I disturbi del comportamento tra neurologia e psichiatria: basi neurobiologiche e sindromi cliniche
1998I disturbi del comportamento tra neurologia e psichiatria: basi neurobiologiche e sindromi cliniche
Masson
1998Phonological Dyslexia: Loss of a Reading-specific Component of the Cognitive Architecture?
Cognitive Neuropsychology
DOI: 10.1080/026432996381836
09/1996Impulse control
Handbook of Aggressive and Destructive Behavior in Psychiatric Patients
DOI: 10.1007/978-1-4615-2403-8
1994Tardive dyskinesia associated with use of metoclopramide in a child
The Journal of Pediatrics
Putnam, P.E. and Orenstein, S.R. and Wessel, H.B. and Stowe, R.M.
DOI: 10.1016/S0022-3476(05)80357-9
1992THE COMPORTMENTAL LEARNING DISABILITIES OF EARLY FRONTAL LOBE DAMAGE
Brain
DOI: 10.1093/brain/113.5.1383
1990Syringomyelia
Current Therapy in Neurological Disease
1986 - Research
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MAGERS (Metabolic and Genetic Explorations in Refractory Schizophrenia)
The MAGERS (Metabolic and Genetic Explorations in Refractory Schizophrenia) study (Robert Stowe, P.I; Precilla Carrion, Co-Project Lead) is a multi-layered clinical. "-omics", and genetic counselling research project that recruited 50 inpatient participants from the tertiary provincial BC Psychosis Unit at UBC Hospital suffering from highly treatment-resistant schizophrenia or schizoaffective disorder. Detailed clinical phenotyping included M.I.N.I psychiatric interviews and multidisciplinary consensus DSM-5 diagnosis, structured birth and childhood trauma histories, neurocognitive assessments, and neurological and dysmorphological examinations.
At entry, intensive biochemical screening for inborn errors of metabolism (IEMs) associated with psychosis was performed (Dr. Graham Sinclair), and clinical chromosomal microarrays were performed in the Royal Columbian Hospital Molecular Cytogenetics Laboratory. DNA and RNA extraction at RCH and in Dr. Michael Kobor’s laboratory was followed by long-read whole genome (PacBio HiFi) sequencing and peripheral blood RNA-Seq (Illumina HiSeq/NovaSeq). Exonic variant prioritization (Pavlidis lab, Indhu Shree Rajan Babu) has been completed, and noncoding variant and RNA analyses are underway. Pharmacogenetic (PGx) variants have been identified and correlated with medication profiles (Dr. Chad Bousman, University of Calgary). Clinically actionable results from CMAs, WGS, and PGx analyses are being returned to care providers, and to patients and families, through psychiatric genetic counselling (the impact of which is also being assessed as a research outcome).
Whole blood, peripheral blood mononuclear cells, serum, plasma, and urine on participants were collected and stored in Drs. Fabio Rossi and Michael Kobor’s labs. A cytokine and inflammatory marker panel has been performed on 25 cases (Dr. Clare Beasley). Proteomics and mass cytometry will be conducted if funding can be secured. Epigenetic analyses and polygenic risk (PRS) and pharmogenic enrichment (PES) scoring are underway in Dr. Murray Cairns’ lab at the University of Newcastle. Translational collaborations include rare variant-focused modelling in iPSCs (Dr. Mahmoud Pouladi; Dr. Michael Ziiller’s lab in Munster), in neurons and model organisms (in labs studying synaptic function), and in Drosophila models (Dr. Douglas Allan, DMCBH).
The main aim of the MAGERS study is to identify potent genomic and epigenomic risk variants indexing key mechanistic derangements driving psychosis in affected individuals, and indexing tractable treatment targets (such as ion channels, neurotransmitter systems, chromatin modifiers, and synaptic and dendritic function and plasticity, and major cellular and immunomodulatory pathways) that can be used to develop precision medicine for psychosis.
Congratulations CIHR Fall 2024 Project Grant recipients
Congratulations to the investigators and their teams who were awarded funding through the Canadian Institutes of Health Research (CIHR) Fall 2024 Project Grant competition!
