Publications
700 results found
Nour MM, Beck K, Liu Y, et al., 2022, Relationship Between Replay-Associated Ripples and Hippocampal N-Methyl-D-Aspartate Receptors: Preliminary Evidence From a PET-MEG Study in Schizophrenia, Schizophrenia Bulletin Open, Vol: 3
Background and Hypotheses: Hippocampal replay and associated high-frequency ripple oscillations are among the best-characterized phenomena in resting brain activity. Replay/ripples support memory consolidation and relational inference, and are regulated by N-methyl-D-aspartate receptors (NMDARs). Schizophrenia has been associated with both replay/ripple abnormalities and NMDAR hypofunction in both clinical samples and genetic mouse models, although the relationship between these 2 facets of hippocampal function has not been tested in humans. Study Design: Here, we avail of a unique multimodal human neuroimaging data set to investigate the relationship between the availability of (intrachannel) NMDAR binding sites in hippocampus, and replay-associated ripple power, in 16 participants (7 nonclinical participants and 9 people with a diagnosis of schizophrenia, PScz). Each participant had both a [18F]GE-179 positron emission tomography (PET) scan (to measure NMDAR availability, VT) and a magnetoencephalography (MEG) scan (to measure offline neural replay and associated high-frequency ripple oscillations, using Temporally Delayed Linear Modeling). Study Results: We show a positive relationship between hippocampal NMDAR availability and replay-associated ripple power. This linkage was evident across control participants (r(5)=.94, P=.002) and PScz (r(7)=.70, P=.04), with no group difference. Conclusions: Our findings provide preliminary evidence for a relationship between hippocampal NMDAR availability and replay-associated ripple power in humans, and haverelevance for NMDAR hypofunction theories of schizophrenia.
Reid MJ, Rogdaki M, Dutan L, et al., 2022, Cell line specific alterations in genes associated with dopamine metabolism and signaling in midbrain dopaminergic neurons derived from 22q11.2 deletion carriers with elevated dopamine synthesis capacity, Schizophrenia Research, ISSN: 0920-9964
Microdeletions at the 22q11.2 locus are associated with increased risk for schizophrenia. Recent work has demonstrated that antipsychotic naïve 22q11.2 carriers display elevated levels of dopamine synthesis capacity (DSC) as assessed by 18F-DOPA PET imaging. While this is consistent with a role for abnormal dopamine function in schizophrenia, it is unclear what molecular changes may be associated with this neuro-imaging endophenotype, and moreover, if these alterations occur independently of clinical presentation. We therefore conducted a pilot study in which we generated human induced pluripotent stem cells (hiPSCs) from two 22q11.2 deletion carriers with elevated DSC in vivo, but distinct clinical presentations. From these and neurotypical control lines we were able to robustly generate midbrain dopaminergic neurons (mDA-neurons). We then assessed whether genes associated with dopamine synthesis, metabolism or signaling show altered expression between genotypes and further between the 22q11.2 deletion lines. Our data showed alterations in expression of genes associated with dopamine metabolism and signaling that differed between the two 22q11.2 hiPSC lines with distinct clinical presentations. This reinforces the importance of considering clinical, genetic and molecular information, when possible, when choosing which donors to generate hiPSCs from, to carry out mechanistic studies.
Howes OD, Thase ME, Pillinger T, 2022, Treatment resistance in psychiatry: state of the art and new directions, MOLECULAR PSYCHIATRY, Vol: 27, Pages: 58-72, ISSN: 1359-4184
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- Citations: 70
Whitehurst T, Howes O, 2022, The role of mitochondria in the pathophysiology of schizophrenia: A critical review of the evidence focusing on mitochondrial complex one, NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, Vol: 132, Pages: 449-464, ISSN: 0149-7634
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- Citations: 7
Lobo MC, Whitehurst TS, Kaar SJ, et al., 2022, New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics, NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, Vol: 132, Pages: 324-361, ISSN: 0149-7634
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- Citations: 23
Osimo E, Sweeney M, De Marvao A, et al., 2021, Adipose tissue dysfunction, inflammation, and insulin resistance: alternative pathways to cardiac remodelling in schizophrenia. A multimodal, case-control study, Translational Psychiatry, Vol: 11, Pages: 1-9, ISSN: 2158-3188
Cardiovascular diseases are the leading cause of death in schizophrenia. Patients with schizophrenia show evidence of concentric cardiac remodelling (CCR), defined as an increase in left-ventricular mass over end-diastolic volumes. CCR is a predictor of cardiac disease, but the molecular pathways leading to this in schizophrenia are unknown. We aimed to explore the relevance of hypertensive and non-hypertensive pathways to CCR and their potential molecular underpinnings in schizophrenia. In this multimodal case–control study, we collected cardiac and whole-body fat magnetic resonance imaging (MRI), clinical measures, and blood levels of several cardiometabolic biomarkers known to potentially cause CCR from individuals with schizophrenia, alongside healthy controls (HCs) matched for age, sex, ethnicity, and body surface area. Of the 50 participants, 34 (68%) were male. Participants with schizophrenia showed increases in cardiac concentricity (d = 0.71, 95% CI: 0.12, 1.30; p = 0.01), indicative of CCR, but showed no differences in overall content or regional distribution of adipose tissue compared to HCs. Despite the cardiac changes, participants with schizophrenia did not demonstrate activation of the hypertensive CCR pathway; however, they showed evidence of adipose dysfunction: adiponectin was reduced (d = −0.69, 95% CI: −1.28, −0.10; p = 0.02), with evidence of activation of downstream pathways, including hypertriglyceridemia, elevated C-reactive protein, fasting glucose, and alkaline phosphatase. In conclusion, people with schizophrenia showed adipose tissue dysfunction compared to body mass-matched HCs. The presence of non-hypertensive CCR and a dysmetabolic phenotype may contribute to excess cardiovascular risk in schizophrenia. If our results are confirmed, acting on this pathway could reduce cardiovascular risk and resultant life-years lost in people with schizophrenia.
Figueiredo IC, Borgan F, Pasternak O, et al., 2021, White-matter free-water diffusion MRI in schizophrenia: a systematic review and meta-analysis, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S551-S552, ISSN: 0924-977X
Dedic N, Dworak H, Zeni C, et al., 2021, Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22
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- Citations: 33
Allen P, Hird EJ, Orlov N, et al., 2021, Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function (vol 11, 607, 2021), TRANSLATIONAL PSYCHIATRY, Vol: 11, ISSN: 2158-3188
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- Citations: 1
Allen P, Hird EJ, Orlov N, et al., 2021, Adverse clinical outcomes in people at clinical high-risk for psychosis related to altered interactions between hippocampal activity and glutamatergic function, TRANSLATIONAL PSYCHIATRY, Vol: 11, ISSN: 2158-3188
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- Citations: 4
Howes O, Cummings C, Heurich M, 2021, Translation From Genes to Mechanism in Schizophrenia: Are Immune-Synaptic Interactions the Missing Link?, BIOLOGICAL PSYCHIATRY, Vol: 90, Pages: 593-595, ISSN: 0006-3223
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- Citations: 2
Plaven-Sigray P, Matheson GJ, Coughlin JM, et al., 2021, Meta-analysis of the glial marker TSPO in psychosis revisited: Reconciling inconclusive findings of patient-control differences, 13th International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: SAGE PUBLICATIONS INC, Pages: 228-229, ISSN: 0271-678X
Tuosto M, Marques TR, Howes OD, et al., 2021, Parametric mapping of [11C]PBR28 brain PET imaging using spectral analysis, 13th International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: SAGE PUBLICATIONS INC, Pages: 220-221, ISSN: 0271-678X
Nordio G, Easmin R, Santangelo B, et al., 2021, [18F]FDOPA PET imaging for prediction of treatment response in psychosis, Publisher: SAGE PUBLICATIONS INC, Pages: 51-52, ISSN: 0271-678X
Shatalina E, Rizzo G, Comley RA, et al., 2021, Multimodal investigation of the synaptic and metabolic basis of low-frequency oscillations in the human brain: A [<SUP>11</SUP>C] UCB-J, [<SUP>18</SUP>F]BCPP-EF and resting state fMRI study, 13th International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: SAGE PUBLICATIONS INC, Pages: 92-92, ISSN: 0271-678X
Pontoriero AD, Santangelo B, Jahuar S, et al., 2021, Automated data quality control in [18F] FDOPA brain PET imaging using deep learning, 13th International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: SAGE PUBLICATIONS INC, Pages: 243-243, ISSN: 0271-678X
Rogeau A, Nordio G, Veronese M, et al., 2021, The relationship between glutamate, dopamine receptors, dopamine release and cortical grey matter: A simultaneous PET-MR study, 13th International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: SAGE PUBLICATIONS INC, Pages: 84-85, ISSN: 0271-678X
Giacomel A, Dipasquale O, Mccutcheon R, et al., 2021, Generation of a normative dopamine neuroreceptor template from [11C] PHNO PET imaging modelling population variability, Publisher: SAGE PUBLICATIONS INC, Pages: 58-59, ISSN: 0271-678X
Millgate E, Kravariti E, Egerton A, et al., 2021, Cross-sectional study comparing cognitive function in treatment responsive versus treatment non-responsive schizophrenia: evidence from the STRATA study, BMJ OPEN, Vol: 11, ISSN: 2044-6055
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- Citations: 1
Shatalina E, Ashok AH, Wall M, et al., 2021, Disrupted association between Mu-opioid receptor levels and resting state activity in patients with schizophrenia: Multimodal imaging study with [<SUP>11</SUP>C]-carfentanil PET and resting state fMRI, 13th International Symposium of Functional Neuroreceptor Mapping of the Living Brain (NRM), Publisher: SAGE PUBLICATIONS INC, Pages: 142-143, ISSN: 0271-678X
Howes OD, McCutcheon R, Owen MJ, et al., 2021, Nuclear Excluded Autism-Associated Phosphatase and Tensin Homolog Mutations Dysregulate Neuronal Growth (vol 84, pg 265, 2018), BIOLOGICAL PSYCHIATRY, Vol: 90, Pages: 505-505, ISSN: 0006-3223
McCutcheon RA, Merritt K, Howes OD, 2021, Dopamine and glutamate in individuals at high risk for psychosis: a meta-analysis of <i>in vivo</i> imaging findings and their variability compared to controls, WORLD PSYCHIATRY, Vol: 20, Pages: 405-416, ISSN: 1723-8617
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- Citations: 12
Marques TR, Veronese M, Owen DR, et al., 2021, Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 48, Pages: 3530-3539, ISSN: 1619-7070
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- Citations: 3
Osimo EF, Brugger SP, Thomas EL, et al., 2021, Body fat volumes and distribution in chronic schizophrenia compared to healthy controls; a cross-sectional MR study
<jats:title>Summary</jats:title><jats:p>People with schizophrenia show higher risk for abdominal obesity than the general population, which could contribute to excess mortality. However, it is unclear whether this is driven by alterations in abdominal fat partitioning. Here, we test the hypothesis that individuals with schizophrenia show a higher proportion of visceral to total body fat measured using MRI. We recruited 38 patients with schizophrenia and 38 healthy controls matched on age, sex, ethnicity and body mass index. We found no significant difference in body fat distribution between groups, suggesting that increased abdominal obesity in schizophrenia is not associated with altered fat distribution.</jats:p>
Eap CB, Grunder G, Baumann P, et al., 2021, Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants, WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, Vol: 22, Pages: 561-628, ISSN: 1562-2975
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- Citations: 13
Correll CU, Howes OD, 2021, Treatment-Resistant Schizophrenia: Definition, Predictors, and Therapy Options., J Clin Psychiatry, Vol: 82
Treatment-resistant schizophrenia (TRS) represents a major clinical challenge. The broad definition of TRS requires nonresponse to at least 2 sequential antipsychotic trials of sufficient dose, duration, and adherence. Several demographic, clinical, and neurologic predictors are associated with TRS. Primary (or early) TRS is present from the beginning of therapy, while patients with secondary (or later-onset) TRS initially respond to antipsychotics but become resistant over time, often after relapses. Guidelines worldwide recognize clozapine as the most effective treatment option for TRS, but clozapine is underused due to various barriers. Importantly, studies indicate that response rates are higher when clozapine is initiated earlier in the treatment course. Side effects are common with clozapine, particularly in the first few weeks, but can mostly be managed without discontinuation; they do require proactive assessment, intervention, and reassurance for patients. Furthermore, plasma leucocyte and granulocyte levels must be monitored weekly during the first 18-26 weeks of treatment, and regularly thereafter, according to country regulations. Therapeutic drug monitoring of clozapine trough plasma levels is helpful to guide dosing, with greatest efficacy at plasma clozapine levels ≥350 µg/L, although this level is not universal. Notably, plasma clozapine levels are generally greater at lower doses in nonsmokers, patients with heavy caffeine consumption, in women, in obese people, in those with inflammation (including COVID-19 infection), and in older individuals. Earlier and broader use of clozapine in patients with TRS is an important measure to improve outcomes of patients with this most severe form of the illness.
Baumeister D, Pillinger T, Howes O, et al., 2021, Psychophysiological stress-reactivity in clinical and non-clinical voice-hearers, SCHIZOPHRENIA RESEARCH, Vol: 235, Pages: 52-59, ISSN: 0920-9964
Pontoriero AD, Nordio G, Easmin R, et al., 2021, Automated Data Quality Control in FDOPA brain PET Imaging using Deep Learning, COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE, Vol: 208, ISSN: 0169-2607
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- Citations: 11
Beck K, Arumuham A, Veronese M, et al., 2021, N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study, TRANSLATIONAL PSYCHIATRY, Vol: 11, ISSN: 2158-3188
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- Citations: 9
Angelescu I, Brugger SP, Borgan F, et al., 2021, The magnitude and variability of brain structural alterations in bipolar disorder: A double meta-analysis of 5534 patients and 6651 healthy controls, JOURNAL OF AFFECTIVE DISORDERS, Vol: 291, Pages: 171-176, ISSN: 0165-0327
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- Citations: 12
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