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Evaluating the Current State of Epilepsy Care in the Province of Ontario
- Christine Van Winssen, Andrea V. Andrade, Danielle M. Andrade, Jorge G. Burneo, Sandrine de Ribaupierre, Elizabeth Donner, Ayman Hassan, George Ibrahim, Kevin C. Jones, Lysa Boissé Lomax, Katherine Muir, Maryam N. Nouri, Nikki Porter, Rajesh Ramachandrannair, Paul Raymond, James Rutka, Michelle J. Shapiro, David A. Steven, Darryl Swain, Taufik Valiante, Sharon Whiting, Robyn Whitney, Ivanna Yau, Tadeu A. Fantaneanu
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- Journal:
- Canadian Journal of Neurological Sciences , First View
- Published online by Cambridge University Press:
- 01 March 2024, pp. 1-3
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There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.
Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study
- Giuseppe D'Andrea, Diego Quattrone, Kathryn Malone, Giada Tripoli, Giulia Trotta, Edoardo Spinazzola, Charlotte Gayer-Anderson, Hannah E Jongsma, Lucia Sideli, Simona A Stilo, Caterina La Cascia, Laura Ferraro, Antonio Lasalvia, Sarah Tosato, Andrea Tortelli, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Paulo Rossi Menezes, Jose Luis Santos, Manuel Arrojo, Julio Bobes, Julio Sanjuán, Miguel Bernardo, Celso Arango, James B Kirkbride, Peter B Jones, Bart P Rutten, Jim Van Os, Jean-Paul Selten, Evangelos Vassos, Franck Schürhoff, Andrei Szöke, Baptiste Pignon, Michael O'Donovan, Alexander Richards, Craig Morgan, Marta Di Forti, Ilaria Tarricone, Robin M Murray
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 30 January 2024, pp. 1-14
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Background
Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.
MethodsWe used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.
ResultsSchizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.
ConclusionsSchizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.
10 Subtyping Serial Position Score Profiles to Investigate the Nature of Memory Impairment in Homeless and Precariously Housed Persons
- Katie C. Benitah, Kristina M. Gicas, Paul W. Jones, Anna M. Petersson, Allen E. Thornton, Tari Buchanan, William G. Honer
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 528-529
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Objective:
Cognitive dysfunction is prominent in homeless and precariously housed persons, and memory dysfunction is the most pervasive domain. The presence of multimorbid physical and mental illness suggests that several underlying mechanisms of memory impairment may be at play. The serial position phenomenon describes the tendency to best recall the beginning (primacy effect) and last (recency effect) words on a supra-span wordlist. Recency recall engages executive and working-memory systems, whereas primacy recall depends on long-term memory. This study investigates memory dysfunction in a homeless and precariously housed sample by identifying and characterizing unique subtypes of serial position profiles on a test of verbal memory.
Participants and Methods:Data were used from a 20-year study of homeless and precariously housed adults recruited from an impoverished neighbourhood in Vancouver, Canada. Participants were sub-grouped according to their serial position profile on the Hopkins Verbal Learning Test-Revised using a latent profile analysis (LPA; n = 411). Paired samples t-tests were conducted to determine differences in percent recall from each word-list region within classes. Linear regression analyses were used to examine between-class differences in mean serial position scores and other cognitive measures (memory, attention, processing speed, cognitive control). Covariates included age, sex, and education.
Results:LPA identified two profiles characterized by (1) reduced primacy relative to recency (RP; n = 150); and (2) reduced recency relative to primacy (RR; n = 261). Pairwise comparisons within the RP class showed that recency was better than primacy (p < .001, d = .66) and middle recall (p < .001, d = .52), with no difference between primacy and middle recall (p = .68, d = .04). All pairwise comparisons differed within the RR class (primacy > middle recall: p < .001, d = 1.85; primacy > recency recall: p < .001, d = 1.32; middle > recency recall: p < .05, d = .132). The RP class had worse performance on measures of total immediate (ß = .47, p < .001) and delayed verbal recall (ß = .32, p < .001); processing speed (ß = .20, p < .001); and cognitive control (ß = .22, p < .001). The RR class made more repetition errors (ß = .25, p < .001).
Conclusions:These findings support substantial heterogeneity in memory functioning in homeless and precariously housed individuals. The RP profile was characterized by poorer cognitive functioning across several domains, which suggests multiple contributions to memory impairment, including dysfunction of long-term memory circuitry. The RR profile with their higher number of repetition errors, may experience difficulties with self-monitoring in verbal learning. Subsequent studies will explore the neurobiological underpinnings of these subgroups to further characterize profiles and identify targets for cognitive intervention.
44 Cognitive Intraindividual Variability as a Predictor of Functional Outcomes in a Sample of Precariously Housed Individuals
- Michelle J Blumberg, Anna Petersson, Paul W Jones, Allen E Thornton, William G Honer, Tari Buchanan, Kristina M Gicas
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 724-725
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Objective:
Precariously housed individuals are exposed to multiple adverse factors negatively impacting neurocognitive functioning. Additionally, this population is subjected to poor life outcomes, such as impaired psychosocial functioning. Neurocognitive functioning plays an important role in psychosocial functioning and may be especially critical for precariously housed individuals who face numerous barriers in their daily lives. However, few studies have explicitly examined the cognitive determinants of functional outcomes in this population. Cognitive intraindividual variability (IIV) involves the study of within-person differences in neurocognitive functioning and has been used as marker of frontal system pathology. Increased IIV has been associated with worse cognitive performance, cognitive decline, and poorer everyday functioning. Hence, IIV may add to the predictive utility of commonly used neuropsychological measures and may serve as an emergent predictor of poor outcomes in at-risk populations. The objective of the current study was to examine IIV as a unique index of the neurocognitive contributions to functional outcomes within a large sample of precariously housed individuals. It was hypothesized that greater IIV would be associated with poorer current (i.e., baseline) and long-term (i.e., up to 12 years) psychosocial functioning.
Participants and Methods:Four hundred and thirty-seven adults were recruited from single-room occupancy hotels located in the Downtown Eastside of Vancouver, Canada (Mage = 44 years, 78% male) between November 2008 and November 2021. Baseline neurocognitive functioning was assessed at study enrolment. Scores from the Social and Occupational Functioning Assessment Scale (SOFAS), the Role Functioning Scale (RFS), the physical component score (PCS) and the mental component score (MCS) of the 36-Item Short Form Survey Instrument were obtained at participants’ baseline assessments and at their last available follow-up assessment to represent baseline and long-term psychosocial functioning, respectively. Using an established formula, an index of IIV was derived using a battery of standardized tests that broadly assessed verbal learning and memory, sustained attention, mental flexibility, and cognitive control. A series of multiple linear regressions were conducted to predict baseline and long-term social and role functioning (average across SOFAS and RFS scores), and PCS and MCS scores from IIV. In each of the models, we also included common predictors of functioning, including a global cognitive composite score, age, and years of education.
Results:The IIV index and the global composite score did not explain a significant proportion of the variance in baseline and long-term social and role functioning (p > .05). However, IIV was a significant predictor of baseline (B = -3.84, p = .021) and long-term (B = -3.58, p = .037) PCS scores, but not MCS scores (p > .05). The global composite score did not predict baseline or long-term PCS scores.
Conclusions:IIV significantly predicted baseline and long-term physical functioning, but not mental functioning or social and role functioning, suggesting that IIV may be a sensitive marker for limitations in everyday functioning due to physical health problems in precariously housed individuals. Critically, the present study is the first to show that IIV may be a useful index for predicting poor long-term health-related outcomes in this population compared to traditional neuropsychological measures.
Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals
- Cecilia A. Hinojosa, Amanda Liew, Xinming An, Jennifer S. Stevens, Archana Basu, Sanne J. H. van Rooij, Stacey L. House, Francesca L. Beaudoin, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. McLean, Kerry J. Ressler, Negar Fani
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 13 June 2023, pp. 338-349
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Background
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
MethodsIn total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
ResultsThree trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
ConclusionsOur findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case–control study
- Giulia Trotta, Victoria Rodriguez, Diego Quattrone, Edoardo Spinazzola, Giada Tripoli, Charlotte Gayer-Anderson, Tom P Freeman, Hannah E Jongsma, Lucia Sideli, Monica Aas, Simona A Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Giuseppe D'Andrea, Andrea Tortelli, Franck Schürhoff, Andrei Szöke, Baptiste Pignon, Jean-Paul Selten, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Paulo Rossi Menezes, Cristina M Del Ben, Jose Luis Santos, Manuel Arrojo, Julio Bobes, Julio Sanjuán, Miquel Bernardo, Celso Arango, James B Kirkbride, Peter B Jones, Alexander Richards, Bart P Rutten, Jim Van Os, Isabelle Austin-Zimmerman, Zhikun Li, Craig Morgan, Pak C Sham, Evangelos Vassos, Chloe Wong, Richard Bentall, Helen L Fisher, Robin M Murray, Luis Alameda, Marta Di Forti, EU-GEI WP2 Group
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- Journal:
- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 04 May 2023, pp. 7375-7384
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Background
Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.
MethodsData were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.
ResultsThe association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.
ConclusionsHarmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case–control study
- Edoardo Spinazzola, Diego Quattrone, Victoria Rodriguez, Giulia Trotta, Luis Alameda, Giada Tripoli, Charlotte Gayer-Anderson, Tom P Freeman, Emma C Johnson, Hannah E Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Giuseppe D'Andrea, Michela Galatolo, Andrea Tortelli, Ilaria Tagliabue, Marco Turco, Maurizio Pompili, Jean-Paul Selten, Lieuwe de Haan, Paulo Rossi Menezes, Cristina M Del Ben, Jose Luis Santos, Manuel Arrojo, Julio Bobes, Julio Sanjuán, Miguel Bernardo, Celso Arango, James B Kirkbride, Peter B Jones, Michael O'Donovan, Bart P Rutten, Jim Van Os, Craig Morgan, Pak C Sham, Isabelle Austin-Zimmerman, Zhikun Li, Evangelos Vassos, EU-GEI WP2 Group, Robin M Murray, Marta Di Forti
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- Journal:
- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 02 May 2023, pp. 7418-7427
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Background
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
MethodsWe used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
ResultsControls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
ConclusionsBoth FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study
- Giuseppe D'Andrea, Jatin Lal, Sarah Tosato, Charlotte Gayer-Anderson, Hannah E. Jongsma, Simona A. Stilo, Els van der Ven, Diego Quattrone, Eva Velthorst, Domenico Berardi, Paulo Rossi Menezes, Celso Arango, Mara Parellada, Antonio Lasalvia, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Lucia Sideli, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Giada Tripoli, Pierre-Michel Llorca, Lieuwe de Haan, Jean-Paul Selten, Andrea Tortelli, Andrei Szöke, Roberto Muratori, Bart P. Rutten, Jim van Os, Peter B. Jones, James B. Kirkbride, Robin M. Murray, Marta di Forti, Ilaria Tarricone, Craig Morgan
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- Journal:
- Psychological Medicine / Volume 53 / Issue 13 / October 2023
- Published online by Cambridge University Press:
- 28 October 2022, pp. 6150-6160
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Background
Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status.
MethodsWe included FEP patients aged 18–64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status.
ResultsWe examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations.
ConclusionsThe higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.
Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study
- Victoria Rodriguez, Luis Alameda, Diego Quattrone, Giada Tripoli, Charlotte Gayer-Anderson, Edoardo Spinazzola, Giulia Trotta, Hannah E. Jongsma, Simona Stilo, Caterina La Cascia, Laura Ferraro, Daniele La Barbera, Antonio Lasalvia, Sarah Tosato, Ilaria Tarricone, Elena Bonora, Stéphane Jamain, Jean-Paul Selten, Eva Velthorst, Lieuwe de Haan, Pierre-Michel Llorca, Manuel Arrojo, Julio Bobes, Miguel Bernardo, Celso Arango, James Kirkbride, Peter B. Jones, Bart P. Rutten, Alexander Richards, Pak C. Sham, Michael O'Donovan, Jim Van Os, Craig Morgan, Marta Di Forti, Robin M. Murray, Evangelos Vassos
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- Journal:
- Psychological Medicine / Volume 53 / Issue 8 / June 2023
- Published online by Cambridge University Press:
- 25 January 2022, pp. 3396-3405
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Background
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
MethodsParticipants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
ResultsIn case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
ConclusionsCombining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
Developing Atom Probe Tomography to Characterize Sr-Loaded Bioactive Glass for Bone Scaffolding
- Yanru Ren, Hélène Autefage, Julian R. Jones, Molly M. Stevens, Paul A.J. Bagot, Michael P. Moody
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- Journal:
- Microscopy and Microanalysis / Volume 28 / Issue 4 / August 2022
- Published online by Cambridge University Press:
- 25 October 2021, pp. 1310-1320
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- August 2022
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In this study, atom probe tomography (APT) was used to investigate strontium-containing bioactive glass particles (BG-Sr10) and strontium-releasing bioactive glass-based scaffolds (pSrBG), both of which are attractive biomaterials with applications in critical bone damage repair. We outline the challenges and corresponding countermeasures of this nonconductive biomaterial for APT sample preparation and experiments, such as avoiding direct contact between focussed ion beam micromanipulators and the extracted cantilever to reduce damage during liftout. Using a low imaging voltage (≤3 kV) and current (≤500 pA) in the scanning electron microscope and a low acceleration voltage (≤2 kV) and current (≤200 pA) in the focussed ion beam prevents tip bending in the final stages of annular milling. To optimize the atom probe experiment, we considered five factors: total detected hits, multiple hits, the background level, the charge-state ratio, and the accuracy of the measured compositions, to explore the optimal laser pulse for BG-Sr10 bioactive glass. We show that a stage temperature of 30 K, 200–250 pJ laser pulse energy, 0.3% detection rate, and 200 kHz pulse rate are optimized experimental parameters for bioactive glass. The use of improved experimental preparation methods and optimized parameters resulted in a 90% successful yield of pSrBG samples by APT.
Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study
- Monica Aas, Luis Alameda, Marta Di Forti, Diego Quattrone, Paola Dazzan, Antonella Trotta, Laura Ferraro, Victoria Rodriguez, Evangelos Vassos, Pak Sham, Giada Tripoli, Caterina La Cascia, Daniele La Barbera, Ilaria Tarricone, Roberto Muratori, Domenico Berardi, Antonio Lasalvia, Sarah Tosato, Andrei Szöke, Pierre-Michel Llorca, Celso Arango, Andrea Tortelli, Lieuwe de Haan, Eva Velthorst, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean-Paul Selten, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Bart P. F. Rutten, Jim van Os, Charlotte Gayer-Anderson, Robin M. Murray, Craig Morgan
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- Journal:
- Psychological Medicine / Volume 53 / Issue 5 / April 2023
- Published online by Cambridge University Press:
- 29 September 2021, pp. 1970-1978
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Background
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
MethodsWe assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.
ResultsThere was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).
ConclusionsOur findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Behavioral measures of impulsivity and compulsivity in adolescents with nonsuicidal self-injury
- Nina M. Lutz, Samuel R. Chamberlain, Ian M. Goodyer, Anupam Bhardwaj, Barbara J. Sahakian, Peter B. Jones, Paul O. Wilkinson
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- Journal:
- CNS Spectrums / Volume 27 / Issue 5 / October 2022
- Published online by Cambridge University Press:
- 23 April 2021, pp. 604-612
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Background
Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents.
MethodsComputerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms.
ResultsAdolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity.
ConclusionsRepetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.
Perceived major experiences of discrimination, ethnic group, and risk of psychosis in a six-country case−control study
- Supriya Misra, Bizu Gelaye, David R. Williams, Karestan C. Koenen, Christina P.C. Borba, Diego Quattrone, Marta Di Forti, Giada Tripoli, Caterina La Cascia, Daniele La Barbera, Laura Ferraro, Ilaria Tarricone, Domenico Berardi, Antonio Lasalvia, Sarah Tosato, Andrei Szöke, Pierre-Michel Llorca, Celso Arango, Andrea Tortelli, Lieuwe de Haan, Eva Velthorst, Julio Bobes, Miguel Bernardo, Julio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Paulo Rossi Menezes, Jean-Paul Selten, Peter B. Jones, Hannah E. Jongsma, James B. Kirkbride, Bart P.F. Rutten, Jim van Os, Robin M. Murray, Charlotte Gayer-Anderson, Craig Morgan
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- Journal:
- Psychological Medicine / Volume 52 / Issue 15 / November 2022
- Published online by Cambridge University Press:
- 02 March 2021, pp. 3668-3676
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Background
Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.
MethodsWe used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.
ResultsReporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).
ConclusionsPervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
Migration history and risk of psychosis: results from the multinational EU-GEI study
- Ilaria Tarricone, Giuseppe D'Andrea, Hannah E. Jongsma, Sarah Tosato, Charlotte Gayer-Anderson, Simona A. Stilo, Federico Suprani, Conrad Iyegbe, Els van der Ven, Diego Quattrone, Marta di Forti, Eva Velthorst, Paulo Rossi Menezes, Celso Arango, Mara Parellada, Antonio Lasalvia, Caterina La Cascia, Laura Ferraro, Julio Bobes, Miguel Bernardo, Iulio Sanjuán, Jose Luis Santos, Manuel Arrojo, Cristina Marta Del-Ben, Giada Tripoli, Pierre-Michel Llorca, Lieuwe de Haan, Jean-Paul Selten, Andrea Tortelli, Andrei Szöke, Roberto Muratori, Bart P. Rutten, Jim van Os, Peter B. Jones, James B. Kirkbride, Domenico Berardi, Robin M. Murray, Craig Morgan
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- Journal:
- Psychological Medicine / Volume 52 / Issue 14 / October 2022
- Published online by Cambridge University Press:
- 10 February 2021, pp. 2972-2984
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Background
Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.
MethodsWe used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.
ResultsIn total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02–3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03–1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672–2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose–response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06–96.47, p = 0.007).
ConclusionsThe cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.
Rethinking the course of psychotic disorders: modelling long-term symptom trajectories
- Craig Morgan, Paola Dazzan, Julia Lappin, Margaret Heslin, Kim Donoghue, Paul Fearon, Peter B Jones, Robin M Murray, Gillian A Doody, Ulrich Reininghaus
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- Journal:
- Psychological Medicine / Volume 52 / Issue 13 / October 2022
- Published online by Cambridge University Press:
- 04 February 2021, pp. 2641-2650
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Background
The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach.
MethodAESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time.
ResultsWe had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory.
ConclusionOur current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.
Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study
- Jutta Joormann, Samuel A. McLean, Francesca L. Beaudoin, Xinming An, Jennifer S. Stevens, Donglin Zeng, Thomas C. Neylan, Gari Clifford, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Gregory Fermann, Lauren A. Hudak, Kamran Mohiuddin, Vishnu Murty, Meghan E. McGrath, John P. Haran, Jose Pascual, Mark Seamon, David A. Peak, Claire Pearson, Robert M. Domeier, Paulina Sergot, Roland Merchant, Leon D. Sanchez, Niels K. Rathlev, William F. Peacock, Steven E. Bruce, Deanna Barch, Diego A. Pizzagalli, Beatriz Luna, Steven E. Harte, Irving Hwang, Sue Lee, Nancy Sampson, Karestan C. Koenen, Kerry J. Ressler, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 52 / Issue 10 / July 2022
- Published online by Cambridge University Press:
- 29 October 2020, pp. 1934-1947
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Background
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
MethodsWe focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
ResultsEight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
ConclusionsThese observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
The incidence of psychotic disorders among migrants and minority ethnic groups in Europe: findings from the multinational EU-GEI study
- Fabian Termorshuizen, Els van der Ven, Ilaria Tarricone, Hannah E. Jongsma, Charlotte Gayer-Anderson, Antonio Lasalvia, Sarah Tosato, Diego Quattrone, Caterina La Cascia, Andrei Szöke, Domenico Berardi, Pierre-Michel Llorca, Lieuwe de Haan, Eva Velthorst, Miguel Bernardo, Julio Sanjuán, Manuel Arrojo, Robin M. Murray, Bart P. Rutten, Peter B. Jones, Jim van Os, James B. Kirkbride, Craig Morgan, Jean-Paul Selten
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- Journal:
- Psychological Medicine / Volume 52 / Issue 7 / May 2022
- Published online by Cambridge University Press:
- 22 September 2020, pp. 1376-1385
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Background
In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: ‘minorities’). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population).
MethodsThe European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20–F33) from 13 sites.
ResultsThe standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32–1.53) in Valencia to 2.47 (95% CI 1.66–3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66–3.93).
ConclusionsIncidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.
Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy
- Sujeevi S. K. Nawaratna, Donald P. McManus, Robin B. Gasser, Paul J. Brindley, Glen M. Boyle, Vanessa Rivera, Shiwanthi L. Ranasinghe, Malcolm K. Jones, Hong You, Geoffrey N. Gobert
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- Journal:
- Parasitology / Volume 147 / Issue 13 / November 2020
- Published online by Cambridge University Press:
- 03 August 2020, pp. 1488-1498
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Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
Association of extent of cannabis use and psychotic like intoxication experiences in a multi-national sample of first episode psychosis patients and controls
- Musa Sami, Diego Quattrone, Laura Ferraro, Giada Tripoli, Erika La Cascia, Charlotte Gayer-Anderson, Jean-Paul Selten, Celso Arango, Miguel Bernardo, Ilaria Tarricone, Andrea Tortelli, Giusy Gatto, Simona del Peschio, Cristina Marta Del-Ben, Bart P. Rutten, Peter B. Jones, Jim van Os, Lieuwe de Haan, Craig Morgan, Cathryn Lewis, Sagnik Bhattacharyya, Tom P. Freeman, Michael Lynskey, Robin M. Murray, Marta Di Forti
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- Journal:
- Psychological Medicine / Volume 51 / Issue 12 / September 2021
- Published online by Cambridge University Press:
- 28 April 2020, pp. 2074-2082
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Background
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
MethodsWe analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
ResultsCaseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
ConclusionsFEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.