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1. Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Author: Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, Torous, J, Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, and Torous, J
Abstract: AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
Published: 2024

2. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Author: Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, Shenton, ME, Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, and Shenton, ME
Abstract: This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
Published: 2024

3. Medication Regimen Complexity In 8 Australian Residential Aged Care Facilities: Impact Of Age, Length Of Stay, Comorbidity, Frailty, And Dependence In Activities Of Daily Living

Author: Chen EYH, Bell JS, Ilomaki J, Keen C, Corlis M, Hogan M, Van Emden J, Hilmer SN, and Sluggett JK
Subjects: Aged, nursing homes, medication regimen complexity, frailty index, activities of daily living, multimorbidity, long-term care facilities., Geriatrics, RC952-954.6
Abstract: Esa YH Chen,1,2 J Simon Bell,1–3 Jenni Ilomaki,2,3 Claire Keen,1 Megan Corlis,2,4 Michelle Hogan,4 Jan Van Emden,2,4 Sarah N Hilmer,2,5 Janet K Sluggett1,2 1Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; 2NHMRC Cognitive Decline Partnership Centre, Hornsby Ku-ring-gai Hospital, Hornsby, NSW, Australia; 3Department of Epidemiology and Preventive Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia; 4Helping Hand Aged Care, North Adelaide, SA, Australia; 5Kolling Institute, Faculty of Medicine and Health, The University of Sydney and Royal North Shore Hospital, St Leonards, NSW, AustraliaCorrespondence: Esa YH ChenCentre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, AustraliaTel +61 3 9903 9533Email Esa.Chen@monash.eduObjective: To explore variation in medication regimen complexity in residential aged care facilities (RACFs) according to resident age, length of stay, comorbidity, dementia severity, frailty, and dependence in activities of daily living (ADLs), and compare number of daily administration times and Medication Regimen Complexity Index (MRCI) as measures of regimen complexity.Methods: This study was a cross-sectional analysis of baseline data from the SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) cluster-randomized controlled trial. The SIMPLER study recruited 242 residents with at least one medication charted for regular administration from 8 RACFs in South Australia. Comorbidity was assessed using the Charlson Comorbidity Index (CCI). Dementia severity was assessed using the Dementia Severity Rating Scale. Frailty was assessed using the FRAIL-NH scale. Dependence in ADLs was assessed using the Katz ADL scale.Results: The median age of participants was 87 years (interquartile range 81–92). Over one-third of participants (n=86, 36%) had 5 or more daily medication administration times. The number of daily administration times and MRCI scores were positively correlated with resident length of stay (rs=0.19; 0.27), FRAIL-NH score (rs=0.23; 0.34) and dependence in ADLs (rs=−0.21; −0.33) (all p
Published: 2019

4. Development and validation of the Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE)

Author: Chen EYH, Sluggett JK, Ilomäki J, Hilmer SN, Corlis M, Picton LJ, Dean L, Alderman CP, Farinola N, Gailer J, Grigson J, Kellie AR, Putsey PJC, Yu S, and Bell JS
Subjects: Medication therapy management, Long-term care, Geriatrics, Drug administration, Medication regimen complexity, RC952-954.6
Abstract: Esa YH Chen,1,2 Janet K Sluggett,1,2 Jenni Ilomäki,1,3 Sarah N Hilmer,2,4 Megan Corlis,2,5 Leonie J Picton,1 Laura Dean,1 Christopher P Alderman,6 Nicholas Farinola,7 Joy Gailer,8 Jane Grigson,5 Andrew R Kellie,9 Peter JC Putsey,5 Solomon Yu,10 J Simon Bell1–3 1Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; 2NHMRC Cognitive Decline Partnership Centre, Sydney Medical School – Northern, Hornsby Ku-ring-gai Hospital, Hornsby, NSW, Australia; 3Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 4Kolling Institute, Sydney Medical School, The University of Sydney and Royal North Shore Hospital, St Leonards, NSW, Australia; 5Helping Hand Aged Care, North Adelaide, SA, Australia; 6School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; 7Department of Clinical Pharmacology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia; 8Drug and Therapeutics Information Service, Repatriation General Hospital, Daw Park, SA, Australia; 9East Adelaide Healthcare, Newton, SA, Australia; 10Aged and Extended Care Services, The Queen Elizabeth Hospital, Woodville South, SA, Australia Background: Residents of aged care facilities use increasingly complex medication regimens. Reducing unnecessary medication regimen complexity (eg, by consolidating the number of administration times or using alternative formulations) may benefit residents and staff. Objective: To develop and validate an implicit tool to facilitate medication regimen simplification in aged care facilities. Method: A purposively selected multidisciplinary expert panel used modified nominal group technique to identify and prioritize factors important in determining whether a medication regimen can be simplified. The five prioritized factors were formulated as questions, pilot-tested using non-identifiable medication charts and refined by panel members. The final tool was validated by two clinical pharmacists who independently applied the tool to a random sample of 50 residents of aged care facilities to identify opportunities for medication regimen simplification. Inter-rater agreement was calculated using Cohen’s kappa.Results: The Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) was developed as an implicit tool comprising of five questions about 1) the resident; 2) regulatory and safety requirements; 3) drug interactions; 4) formulation; and 5) facility and follow-up considerations. Using MRS GRACE, two pharmacists independently simplified medication regimens for 29/50 and 30/50 residents (Cohen’s kappa=0.38, 95% CI 0.12–0.64), respectively. Simplification was possible for all residents with five or more administration times. Changing an administration time comprised 75% of the two pharmacists’ recommendations.Conclusions: Using MRS GRACE, two clinical pharmacists independently simplified over half of residents’ medication regimens with fair agreement. MRS GRACE is a promising new tool to guide medication regimen simplification in aged care. Keywords: medication therapy management, long-term care, geriatrics, drug administration, medication regimen complexity
Published: 2018

5. The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial

Author: Susai, SR, Mongan, D, Healy, C, Cannon, M, Nelson, B, Markulev, C, Schäfer, MR, Berger, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, Alison, McGorry, PD, Föcking, M, Cotter, D, Amminger, GP, Susai, SR, Mongan, D, Healy, C, Cannon, M, Nelson, B, Markulev, C, Schäfer, MR, Berger, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, Alison, McGorry, PD, Föcking, M, Cotter, D, and Amminger, GP
Published: 2022

6. Twelve-Month Cognitive Trajectories in Individuals at Ultra-High Risk for Psychosis: A Latent Class Analysis.

Author: Allott, K, Schmidt, SJ, Yuen, HP, Wood, SJ, Nelson, B, Markulev, C, Lavoie, S, Brewer, WJ, Schäfer, MR, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR, Amminger, P, McGorry, PD, Hartmann, J, Allott, K, Schmidt, SJ, Yuen, HP, Wood, SJ, Nelson, B, Markulev, C, Lavoie, S, Brewer, WJ, Schäfer, MR, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR, Amminger, P, McGorry, PD, and Hartmann, J
Abstract: Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved ("caught up") to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.
Published: 2022

7. Machine learning based prediction and the influence of complement - Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial

Author: Susai, SR, Mongan, D, Healy, C, Cannon, M, Cagney, G, Wynne, K, Byrne, JF, Markulev, C, Schafer, MR, Berger, M, Mossaheb, N, Schlogelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Street, R, Thompson, A, Yung, AR, Nelson, B, McGorry, PD, Focking, M, Amminger, GP, Cotter, D, Susai, SR, Mongan, D, Healy, C, Cannon, M, Cagney, G, Wynne, K, Byrne, JF, Markulev, C, Schafer, MR, Berger, M, Mossaheb, N, Schlogelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Street, R, Thompson, A, Yung, AR, Nelson, B, McGorry, PD, Focking, M, Amminger, GP, and Cotter, D
Abstract: BACKGROUND: Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. MATERIALS AND METHODS: We carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. RESULTS AND CONCLUSION: A prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two protei
Published: 2022

8. Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis

Author: Susai, SR, Healy, C, Mongan, D, Heurich, M, Byrne, JF, Cannon, M, Cagney, G, Wynne, K, Markulev, C, Schafer, MR, Berger, M, Mossaheb, N, Schlogelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Street, R, Thompson, A, Yung, AR, Nelson, B, McGorry, PD, Focking, M, Amminger, GP, Cotter, D, Susai, SR, Healy, C, Mongan, D, Heurich, M, Byrne, JF, Cannon, M, Cagney, G, Wynne, K, Markulev, C, Schafer, MR, Berger, M, Mossaheb, N, Schlogelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Street, R, Thompson, A, Yung, AR, Nelson, B, McGorry, PD, Focking, M, Amminger, GP, and Cotter, D
Abstract: Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.
Published: 2022

9. Discovering the structure and organization of a free Cantonese emotion-label word association graph to understand mental lexicons of emotions.

Author: Wong, TY, Fang, Z, Yu, YT, Cheung, C, Hui, CLM, Elvevåg, B, De Deyne, S, Sham, PC, Chen, EYH, Wong, TY, Fang, Z, Yu, YT, Cheung, C, Hui, CLM, Elvevåg, B, De Deyne, S, Sham, PC, and Chen, EYH
Abstract: Emotions are not necessarily universal across different languages and cultures. Mental lexicons of emotions depend strongly on contextual factors, such as language and culture. The Chinese language has unique linguistic properties that are different from other languages. As a main variant of Chinese, Cantonese has some emotional expressions that are only used by Cantonese speakers. Previous work on Chinese emotional vocabularies focused primarily on Mandarin. However, little is known about Cantonese emotion vocabularies. This is important since both language variants might have distinct emotional expressions, despite sharing the same writing system. To explore the structure and organization of Cantonese-label emotion words, we selected 79 highly representative emotion cue words from an ongoing large-scale Cantonese word association study (SWOW-HK). We aimed to identify the categories of these emotion words and non-emotion words that related to emotion concepts. Hierarchical cluster analysis was used to generate word clusters and investigate the underlying emotion dimensions. As the cluster quality was low in hierarchical clustering, we further constructed an emotion graph using a network approach to explore how emotions are organized in the Cantonese mental lexicon. With the support of emotion knowledge, the emotion graph defined more distinct emotion categories. The identified network communities covered basic emotions such as love, happiness, and sadness. Our results demonstrate that mental lexicon graphs constructed from free associations of Cantonese emotion-label words can reveal fine categories of emotions and their relevant concepts.
Published: 2022

10. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Blokland, GAM, Grove, J, Chen, CY, Cotsapas, C, Tobet, S, Handa, R, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Blokland, GAM, Grove, J, Chen, CY, Cotsapas, C, Tobet, S, Handa, R, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, and Hirschhorn, JN
Abstract: Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functio
Published: 2021

11. The association between migrant status and transition in an ultra-high risk for psychosis population

Author: O'Donoghue, B, Geros, H, Sizer, H, Addington, J, Amminger, GP, Beaden, CE, Cadenhead, KS, Cannon, TD, Cornblatt, BA, Berger, GE, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Ising, HK, Lavoie, S, Lin, A, Markulev, C, Mathalon, DH, McGlashan, TH, Mifsud, NG, Mossaheb, N, Nieman, DH, Nordentoft, M, Perkins, DO, Riecher-Roessler, A, Schaefer, MR, Schloegelhofer, M, Seidman, LJ, Smesny, S, Thompson, A, Tsuang, MT, van der Gaag, M, Verma, S, Walker, EF, Wood, SJ, Woods, SW, Yuen, HP, Yung, AR, McGorry, PD, Nelson, B, O'Donoghue, B, Geros, H, Sizer, H, Addington, J, Amminger, GP, Beaden, CE, Cadenhead, KS, Cannon, TD, Cornblatt, BA, Berger, GE, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Ising, HK, Lavoie, S, Lin, A, Markulev, C, Mathalon, DH, McGlashan, TH, Mifsud, NG, Mossaheb, N, Nieman, DH, Nordentoft, M, Perkins, DO, Riecher-Roessler, A, Schaefer, MR, Schloegelhofer, M, Seidman, LJ, Smesny, S, Thompson, A, Tsuang, MT, van der Gaag, M, Verma, S, Walker, EF, Wood, SJ, Woods, SW, Yuen, HP, Yung, AR, McGorry, PD, and Nelson, B
Abstract: PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.
Published: 2021

12. Omega-3 fatty acids and neurocognitive ability in young people at ultra-high risk for psychosis

Author: McLaverty, A, Allott, KA, Berger, M, Hester, R, McGorry, PD, Nelson, B, Markulev, C, Yuen, HP, Schaefer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Thompson, A, Yung, AR, Amminger, GP, McLaverty, A, Allott, KA, Berger, M, Hester, R, McGorry, PD, Nelson, B, Markulev, C, Yuen, HP, Schaefer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Thompson, A, Yung, AR, and Amminger, GP
Abstract: BACKGROUND: Neurocognitive impairments are core early features of psychosis and are observed in those at ultra-high risk (UHR) for psychosis. The aim of the present study was to explore whether neurocognition is associated with polyunsaturated fatty acids (PUFAs), as has been observed in other clinical populations. METHOD: Erythrocyte levels of total omega-3-and omega-6 PUFAs the omega-3/omega-6 ratio, were measured in 265 UHR individuals. Six domains of neurocognition as well a Composite Score, were assessed using the Brief Assessment of Cognition in Schizophrenia. Pearson's correlations were used to assess the relationship between PUFAs and neurocognition. All analyses were controlled for tobacco smoking. RESULTS: Verbal Fluency correlated positively with eicosapentaenoic acid (P = .024) and alpha-linolenic acid (P = .01), and negatively with docosahexanoic acid (P = .007) and Working Memory positively correlated with omega-3/omega-6 ratio (P = .007). CONCLUSIONS: The current results provide support for a relationship between Verbal Fluency and omega-3 PUFAs in UHR. Further investigation is required to elucidate whether these biomarkers are useful as risk markers or in understanding the biological underpinning of neurocognitive impairment in this population.
Published: 2021

13. Characterization and prediction of clinical pathways of vulnerability to psychosis through graph signal processing

Author: Sandini, C, Zoller, D, Schneider, M, Tarun, A, Armondo, M, Nelson, B, Amminger, PG, Yuen, HP, Markulev, C, Schaffer, MR, Mossaheb, N, Schlogelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Thompson, A, Yung, AR, McGorry, PD, Van De Ville, D, Eliez, S, Sandini, C, Zoller, D, Schneider, M, Tarun, A, Armondo, M, Nelson, B, Amminger, PG, Yuen, HP, Markulev, C, Schaffer, MR, Mossaheb, N, Schlogelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Thompson, A, Yung, AR, McGorry, PD, Van De Ville, D, and Eliez, S
Abstract: Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Network analysis techniques have emerged as alternative approaches that could help shed light on the complex dynamics of early psychopathology. The present study attempts to address the two main limitations that have in our opinion hindered the application of network approaches in the clinical setting. Firstly, we show that a multi-layer network analysis approach, can move beyond a static view of psychopathology, by providing an intuitive characterization of the role of specific symptoms in contributing to clinical trajectories over time. Secondly, we show that a Graph-Signal-Processing approach, can exploit knowledge of longitudinal interactions between symptoms, to predict clinical trajectories at the level of the individual. We test our approaches in two independent samples of individuals with genetic and clinical vulnerability for developing psychosis. Novel network approaches can allow to embrace the dynamic complexity of early psychopathology and help pave the way towards a more a personalized approach to clinical care.
Published: 2021

14. An overview of a specialized intervention service for adult onset first-episode psychosis - The Jockey Club Early Psychosis (JCEP) Project: B85

Author: Lai, DC, Tam, WWY, Hui, CLM, Chang, WC, Chan, SKW, Lee, EHM, and Chen, EYH
Published: 2012

15. Short-term improvement in visual memory by a proprietary North American ginseng extract in stable schizophrenia

Author: Clement, Y and Chen, EYH
Published: 2012
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16. Distress related to attenuated psychotic symptoms: Static and dynamic association with transition to psychosis, non-remission and transdiagnostic symptomatology in clinical high-risk patients in an international intervention trial.

Author: Nelson, B, Yuen, HP, Amminger, GP, Berger, G, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Lavoie, S, Markulev, C, Mossaheb, N, Nieman, DH, Nordentoft, M, Polari, A, Riecher-Rössler, A, Schäfer, MR, Schlögelhofer, M, Smesny, S, Tedja, A, Thompson, A, Verma, S, Yung, AR, McGorry, PD, Nelson, B, Yuen, HP, Amminger, GP, Berger, G, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Lavoie, S, Markulev, C, Mossaheb, N, Nieman, DH, Nordentoft, M, Polari, A, Riecher-Rössler, A, Schäfer, MR, Schlögelhofer, M, Smesny, S, Tedja, A, Thompson, A, Verma, S, Yung, AR, and McGorry, PD
Abstract: This study examined whether distress in relation to attenuated psychotic symptoms (DAPS) is associated with clinical outcomes in an ultra-high-risk (UHR) for psychosis sample. We also investigated whether DAPS is associated with cognitive style (attributional style and cognitive biases) and whether amount of psychosocial treatment provided is associated with reduction in DAPS. The study was a secondary analysis of the 'Neurapro' clinical trial of omega-3 fatty acids. 304 UHR patients were recruited across ten early intervention services. Data from baseline assessment, regular assessments over 12 months and medium term follow up (mean=3.4 years) were used for analysis. Findings indicated: a positive association between DAPS assessed over time and transition to psychosis; a significant positive association between baseline and longitudinal DAPS and transdiagnostic clinical and functional outcomes; a significant positive association between baseline and longitudinal DAPS and non-remission of UHR status. There was no relationship between severity of DAPS and cognitive style. A greater amount of psychosocial treatment (cognitive-behavioural case management) was associated with an increase in DAPS scores. The study indicates that UHR patients who are more distressed by their attenuated psychotic symptoms are more likely to have a poorer clinical trajectory transdiagnostically. Assessment of DAPS may therefore function as a useful marker of risk for a range of poor outcomes. The findings underline the value of repeated assessment of variables and incorporation of dynamic change into predictive modelling. More research is required into mechanisms driving distress associated with symptoms and the possible bidirectional relationship between symptom severity and associated distress.
Published: 2020

17. Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes

Author: Youn, S, Phillips, LJ, Amminger, GP, Berger, G, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Lavoie, S, Markulev, C, McGorry, PD, Mossaheb, N, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Schafer, MR, Schloegelhofer, M, Smesny, S, Thompson, A, Verma, S, Yuen, HP, Yung, AR, Nelson, B, Youn, S, Phillips, LJ, Amminger, GP, Berger, G, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Lavoie, S, Markulev, C, McGorry, PD, Mossaheb, N, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Schafer, MR, Schloegelhofer, M, Smesny, S, Thompson, A, Verma, S, Yuen, HP, Yung, AR, and Nelson, B
Abstract: There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.
Published: 2020

18. Characterization and Prediction of Clinical Pathways of Vulnerability to Psychosis through Graph Signal Processing

Author: Sandini, C, Zöller, D, Schneider, M, Tarun, A, Armando, M, Nelson, B, Mallawaarachchi, SR, Amminger, P, Farhall, J, Bolt, L, Yuen, HP, Markulev, C, Schäfer, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, I, Berger, GE, Chen, EYH, de Haan, L, Nieman, D, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR, Allott, K, McGorry, P, Van De Ville, D, Eliez, S, Sandini, C, Zöller, D, Schneider, M, Tarun, A, Armando, M, Nelson, B, Mallawaarachchi, SR, Amminger, P, Farhall, J, Bolt, L, Yuen, HP, Markulev, C, Schäfer, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, I, Berger, GE, Chen, EYH, de Haan, L, Nieman, D, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR, Allott, K, McGorry, P, Van De Ville, D, and Eliez, S
Abstract: There is a growing recognition that psychiatric symptoms have the potential to causally interact with one another. Particularly in the earliest stages of psychopathology dynamic interactions between symptoms could contribute heterogeneous and cross-diagnostic clinical evolutions. Current clinical approaches attempt to merge clinical manifestations that co-occur across subjects and could therefore significantly hinder our understanding of clinical pathways connecting individual symptoms. Network approaches have the potential to shed light on the complex dynamics of early psychopathology. In the present manuscript we attempt to address 2 main limitations that have in our opinion hindered the application of network approaches in the clinical setting. The first limitation is that network analyses have mostly been applied to cross-sectional data, yielding results that often lack the intuitive interpretability of simpler categorical or dimensional approaches. Here we propose an approach based on multi-layer network analysis that offers an intuitive low-dimensional characterization of longitudinal pathways involved in the evolution of psychopathology, while conserving high-dimensional information on the role of specific symptoms. The second limitation is that network analyses typically characterize symptom connectivity at the level of a population, whereas clinical practice deals with symptom severity at the level of the individual. Here we propose an approach based on graph signal processing that exploits knowledge of network interactions between symptoms to predict longitudinal clinical evolution at the level of the individual. We test our approaches in two independent samples of individuals with genetic and clinical vulnerability for developing psychosis.
Published: 2020

19. Trajectories of symptom severity and functioning over a three-year period in a psychosis high-risk sample: A secondary analysis of the Neurapro trial

Author: Hartmann, JA, Schmidt, SJ, McGorry, PD, Berger, M, Berger, GE, Chen, EYH, de Haan, L, Hickie, IB, Lavoie, S, Markulev, C, Mossaheb, N, Nieman, DH, Nordentoft, M, Polari, A, Riecher-Rossler, A, Schafer, MR, Schlogelhofer, M, Smesny, S, Thompson, A, Verma, SK, Yuen, HP, Yung, AR, Amminger, GP, Nelson, B, Hartmann, JA, Schmidt, SJ, McGorry, PD, Berger, M, Berger, GE, Chen, EYH, de Haan, L, Hickie, IB, Lavoie, S, Markulev, C, Mossaheb, N, Nieman, DH, Nordentoft, M, Polari, A, Riecher-Rossler, A, Schafer, MR, Schlogelhofer, M, Smesny, S, Thompson, A, Verma, SK, Yuen, HP, Yung, AR, Amminger, GP, and Nelson, B
Abstract: The Ultra-High Risk (UHR) for psychosis group is known to be heterogeneous with diverse outcomes. This study aimed to: 1. Identify subclasses of UHR individuals based on trajectories of symptomatic and functional change over time, 2. Identify predictors of these trajectories. A sample of 304 UHR individuals participating in the Neurapro trial were followed over an average of 40 months. All participants received cognitive-behavioural case management (CBCM). Symptomatic and functional profiles were investigated using latent class growth analysis. Multinomial regression was employed to investigate predictors of classes. Identified trajectories showed mostly parallel slopes (i.e. improving symptoms/functioning over time), which were primarily distinct regarding the severity of symptomatology/level of functioning at baseline (i.e. the intercept). Higher symptomatic/lower functioning classes were predicted by higher substance use, older age, female gender, and lower cognitive functioning. No divergent trajectories were identified as all classes improved over time. This may reflect effective treatment through CBCM, natural illness course, or effective engagement with mental health services. Nonetheless, classes highest in symptoms/lowest in functioning still showed considerable impairment during follow-up, highlighting the need for targeted intervention in these subgroups. The study emphasizes the need for more clinical attention directed towards UHR patients being female or using substances.
Published: 2020

20. Do schizotypal or borderline personality disorders predict onset of psychotic disorder or persistent attenuated psychotic symptoms in patients at high clinical risk?

Author: Hadar, H, Zhang, H, Phillips, LJ, Amminger, GP, Berger, GE, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Lavoie, S, Markulev, C, McGorry, PD, Mossaheb, N, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Schafer, MR, Schloegelhofer, M, Smesny, S, Thompson, A, Verma, S, Yuen, HP, Yung, AR, Nelson, B, Hadar, H, Zhang, H, Phillips, LJ, Amminger, GP, Berger, GE, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Lavoie, S, Markulev, C, McGorry, PD, Mossaheb, N, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Schafer, MR, Schloegelhofer, M, Smesny, S, Thompson, A, Verma, S, Yuen, HP, Yung, AR, and Nelson, B
Published: 2020

21. Cognitive functioning in ultra -high risk for psychosis individuals with and without depression: Secondary analysis of findings from the NEURAPRO randomized clinical trial

Author: Mallawaarachchi, SR, Amminger, GP, Farhall, J, Bolt, LK, Nelson, B, Yuen, HP, McGorry, PD, Markulev, C, Schaefer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Thompson, A, Yung, AR, Allott, KA, Mallawaarachchi, SR, Amminger, GP, Farhall, J, Bolt, LK, Nelson, B, Yuen, HP, McGorry, PD, Markulev, C, Schaefer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Thompson, A, Yung, AR, and Allott, KA
Abstract: Neurocognitive impairments are well established in both ultra-high risk (UHR) for psychosis and major depressive disorder (MDD). Despite this understanding, investigation of neurocognitive deficits in UHR individuals with MDD and its association with MDD within this population, has been scarce. Hence, this study aimed to examine any differences in neurocognition at baseline between those with MDD at baseline and those with no history of MDD, as well as determine whether neurocognitive variables are significantly associated with meeting criteria for MDD at follow-up, while controlling for relevant clinical variables, within a UHR cohort. Data analysis was conducted on 207 participants whose baseline neurocognition was assessed using Brief Assessment of Cognition for Schizophrenia, as part of a trial of omega-3 fatty acids (NEURAPRO) for UHR individuals. While baseline MDD was the strongest predictor, poorer verbal memory and higher verbal fluency were significantly associated with MDD at 12 months (p = .04 and 0.026, respectively). Further, higher processing speed was significantly associated with MDD at medium-term follow-up (p = .047). These findings outline that neurocognitive skills were independently associated with meeting criteria for MDD at follow-up within UHR individuals, with novel findings of better verbal fluency and processing speed being linked to MDD outcomes. Hence, neurocognitive performance should be considered as a marker of risk for MDD outcomes and a target for management of MDD in UHR.
Published: 2020

22. T34. THE IMPACT OF ANTIDEPRESSANT USE ON THE TRANSITION TO PSYCHOSIS RATE IN THE NEURAPRO TRIAL

Author: Schlögelhofer, M, McGorry, PD, Nelson, B, Berger, M, Markulev, C, Pan Yuen, H, Schäfer, MR, Mossaheb, N, Smesny, S, Hickie, IB, Berger, G, Chen, EYH, De Haan, L, Nieman, D, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, A, Amminger, GP, Schlögelhofer, M, McGorry, PD, Nelson, B, Berger, M, Markulev, C, Pan Yuen, H, Schäfer, MR, Mossaheb, N, Smesny, S, Hickie, IB, Berger, G, Chen, EYH, De Haan, L, Nieman, D, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, A, and Amminger, GP
Abstract: Background Over the last two decades, several randomised controlled trials (RCTs) have indicated that preventive psychosocial, pharmacologic (Van der Gaag et al. 2013), and nutritional interventions (Amminger et al. 2010) are likely to be beneficial in people at ultra-high risk (UHR) of psychosis, in terms of delaying or preventing a transition to psychosis. Antidepressant medication is commonly prescribed in young people at UHR for psychosis; however, the evidence regarding its efficacy for psychosis prevention is limited (Fusar-Poli et al. 2007; Cornblatt et al. 2007; Fusar-Poli et al. 2015). The main aim of the present study is to investigate the impact of concomitant AD medication on the transition to psychosis rate in young people at ultra-high risk of psychosis who participated in the NEURAPRO trial (McGorry et al. 2017). Methods In this secondary analysis, data from 304 participants of a multicenter, double-blind, placebo-controlled, randomized clinical trial (NEURAPRO) of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) were included. During the trial, concomitant antidepressant medication was permitted for treatment of moderate to severe major depressive disorder (a score of ≥ 21 on the Montgomery-Asberg Depression Rating Scale, MADRS) in all participants. Results Of 304 participants, 189 (62.2%) were treated with ADs. 98 (64.1%) of those were in the omega-3 group and 91 (60.3%) in the placebo group. The transition rate to psychosis was higher in individuals who received AD treatment (13.2%; 25 of 189) as in individuals without ADs (6.1%; 7 of 115). The Kaplan-Meier survival curve estimated a group difference of X2 = 3.237, P = .072 (log rank test). Discussion Antidepressants are widely used in early psychosis. This analysis does not support the view that antidepressants may have reduced the transition to psychosis rate in this cohort. The findings are limited by the fact that antidepressants were prescribed based on clinical discretion. A rando
Published: 2020

23. Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial (vol 10, 393, 2019)

Author: Berger, M, Nelson, B, Markulev, C, Yuen, HP, Schafer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Mitchell, TW, Meyer, BJ, Thompson, A, Yung, AR, McGorry, PD, Amminger, GP, Berger, M, Nelson, B, Markulev, C, Yuen, HP, Schafer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Mitchell, TW, Meyer, BJ, Thompson, A, Yung, AR, McGorry, PD, and Amminger, GP
Abstract: [This corrects the article DOI: 10.3389/fpsyt.2019.00393.].
Published: 2020

24. Altered risky decision making in patients with early non-affective psychosis

Author: Chang Wc, Chen Eyh, Siu Cmw, Chong Csy, Chan Skw, Lo Tl, Lee Tmc, Lee Emh, Sun Yn, Hui Clm, and Luk Msk
Subjects: Psychosis, Decision Making, Poison control, Impulsivity, Suicide prevention, 03 medical and health sciences, 0302 clinical medicine, Risk-Taking, Injury prevention, Medicine, Humans, Pharmacology (medical), Biological Psychiatry, Risk aversion, business.industry, Human factors and ergonomics, Cognition, General Medicine, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Psychotic Disorders, Impulsive Behavior, Schizophrenia, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Abnormal risky decision making may represent an important factor contributing to functional impairment in psychotic disorders. Previous research revealed impaired decision making under risk in patients with chronic schizophrenia. However, risky decision making is under-studied in the early course of illness. We examined risky decision making in 33 patients with early non-affective psychosis and 32 demographically matched controls, using two well-validated experimental paradigms, balloon analogue risk task (BART) and Risky-Gains task (RGT), which modeled and assessed actual risk-taking behaviors in deliberative and time-pressured decision-making situations, respectively. Our results showed that patients exhibited suboptimal decision making on the BART and were more risk averse than controls by having fewer average balloon pumps in non-burst trials, lower explosion rate and lower total points gained. On the RGT, patients also behaved more conservatively than controls, with lower overall rate in choosing the risky option. Intriguingly, patients performed comparably to controls in adjusting risk-taking pattern following punished trials, suggesting relatively preserved sensitivity to punishment in early psychosis. Risk-taking measures showed no significant correlations with any symptom dimensions, impulsivity traits, cognitive functions or antipsychotic treatment after correcting for multiple comparisons. This study is the first to investigate risk-taking propensity in early psychosis based on BART/RGT performance, and consistently indicate that patients with early psychosis displayed altered risky decision making with increased risk aversion relative to healthy participants. Further investigation is warranted to clarify the longitudinal course of aberrant risky decision making and its relationship with functional outcome in early psychosis.
Published: 2018

25. Medication Regimen Complexity In 8 Australian Residential Aged Care Facilities: Impact Of Age, Length Of Stay, Comorbidity, Frailty, And Dependence In Activities Of Daily Living

Author: Chen, EYH, Bell, JS, Ilomaki, J, Keen, C, Corlis, M, Hogan, M, Van Emden, J, Hilmer, SN, Sluggett, JK, Chen, EYH, Bell, JS, Ilomaki, J, Keen, C, Corlis, M, Hogan, M, Van Emden, J, Hilmer, SN, and Sluggett, JK
Abstract: OBJECTIVE: To explore variation in medication regimen complexity in residential aged care facilities (RACFs) according to resident age, length of stay, comorbidity, dementia severity, frailty, and dependence in activities of daily living (ADLs), and compare number of daily administration times and Medication Regimen Complexity Index (MRCI) as measures of regimen complexity. METHODS: This study was a cross-sectional analysis of baseline data from the SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) cluster-randomized controlled trial. The SIMPLER study recruited 242 residents with at least one medication charted for regular administration from 8 RACFs in South Australia. Comorbidity was assessed using the Charlson Comorbidity Index (CCI). Dementia severity was assessed using the Dementia Severity Rating Scale. Frailty was assessed using the FRAIL-NH scale. Dependence in ADLs was assessed using the Katz ADL scale. RESULTS: The median age of participants was 87 years (interquartile range 81-92). Over one-third of participants (n=86, 36%) had 5 or more daily medication administration times. The number of daily administration times and MRCI scores were positively correlated with resident length of stay (rs=0.19; 0.27), FRAIL-NH score (rs=0.23; 0.34) and dependence in ADLs (rs=-0.21; -0.33) (all p<0.01). MRCI was weakly negatively correlated with CCI score (rs=-0.16; p=0.013). Neither number of daily administration times nor MRCI score were correlated with age or dementia severity. In multivariate analysis, frailty was associated with number of daily administration times (OR: 1.13, 95% CI: 1.03-1.24) and MRCI score (OR: 1.26, 95% CI: 1.13-1.41). Dementia severity was inversely associated with both multiple medication administration times (OR: 0.97, 95% CI: 0.94-0.99) and high MRCI score (OR: 0.95, 95% CI: 0.92-0.98). CONCLUSION: Residents with longer lengths of stay, more dependent in ADLs and most frail had the most complex medication regime
Published: 2019

26. Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial

Author: Berger, M, Nelson, B, Markulev, C, Yuen, HP, Schafer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Thompson, A, Yung, AR, McGorry, PD, Amminger, GP, Berger, M, Nelson, B, Markulev, C, Yuen, HP, Schafer, MR, Mossaheb, N, Schloegelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rossler, A, Verma, S, Thompson, A, Yung, AR, McGorry, PD, and Amminger, GP
Abstract: Background: Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods: A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results: The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic ac
Published: 2019

27. Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Author: Harold, D, Connolly, S, Riley, BP, Kendler, KS, McCarthy, SE, McCombie, WR, Richards, A, Owen, MJ, O'Donovan, MC, Walters, J, Donnelly, P, Bates, L, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Hopkins, L, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Ripke, S, Neale, BM, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M-L, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chan, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Lee, J, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Muller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Buxbaum, JD, Borglum, AD, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, Harold, D, Connolly, S, Riley, BP, Kendler, KS, McCarthy, SE, McCombie, WR, Richards, A, Owen, MJ, O'Donovan, MC, Walters, J, Donnelly, P, Bates, L, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Hopkins, L, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Ripke, S, Neale, BM, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M-L, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chan, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Lee, J, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Muller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Buxbaum, JD, Borglum, AD, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, and Sullivan, PF
Abstract: Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.
Published: 2019

28. A correction for sample overlap in genome-wide association studies in a polygenic pleiotropy-informed framework

Author: LeBlanc, M, Zuber, V, Thompson, WK, Andreassen, OA, Frigessi, A, Andreassen, BK, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crespo-Facorro, B, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Favero, JD, DeLisi, LE, Demontis, D, Dikeos, D, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Gershon, ES, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, LeBlanc, M, Zuber, V, Thompson, WK, Andreassen, OA, Frigessi, A, Andreassen, BK, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crespo-Facorro, B, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Favero, JD, DeLisi, LE, Demontis, D, Dikeos, D, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Gershon, ES, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, and Hirschhorn, JN
Abstract: Background: There is considerable evidence that many complex traits have a partially shared genetic basis, termed pleiotropy. It is therefore useful to consider integrating genome-wide association study (GWAS) data across several traits, usually at the summary statistic level. A major practical challenge arises when these GWAS have overlapping subjects. This is particularly an issue when estimating pleiotropy using methods that condition the significance of one trait on the signficance of a second, such as the covariate-modulated false discovery rate (cmfdr). Results: We propose a method for correcting for sample overlap at the summary statistic level. We quantify the expected amount of spurious correlation between the summary statistics from two GWAS due to sample overlap, and use this estimated correlation in a simple linear correction that adjusts the joint distribution of test statistics from the two GWAS. The correction is appropriate for GWAS with case-control or quantitative outcomes. Our simulations and data example show that without correcting for sample overlap, the cmfdr is not properly controlled, leading to an excessive number of false discoveries and an excessive false discovery proportion. Our correction for sample overlap is effective in that it restores proper control of the false discovery rate, at very little loss in power. Conclusions: With our proposed correction, it is possible to integrate GWAS summary statistics with overlapping samples in a statistical framework that is dependent on the joint distribution of the two GWAS.
Published: 2018

29. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Author: Ruderfer, DM, Ripke, S, McQuillin, A, Boocock, J, Stahl, EA, Pavlides, JMW, Mullins, N, Charney, AW, Ori, APS, Loohuis, LMO, Domenici, E, Di Florio, A, Papiol, S, Kalman, JL, Trubetskoy, V, Adolfsson, R, Agartz, I, Agerbo, E, Akil, H, Albani, D, Albus, M, Alda, M, Alexander, M, Alliey-Rodriguez, N, Als, TD, Amin, F, Anjorin, A, Arranz, MJ, Awasthi, S, Bacanu, SA, Badner, JA, Baekvad-Hansen, M, Bakker, S, Band, G, Barchas, JD, Barroso, I, Bass, N, Bauer, M, Baune, BT, Begemann, M, Bellenguez, C, Belliveau, RA, Bellivier, F, Bender, S, Bene, J, Bergen, SE, Berrettini, WH, Bevilacqua, E, Biernacka, JM, Bigdeli, TB, Black, DW, Blackburn, H, Blackwell, JM, Blackwood, DHR, Pedersen, CB, Boehnke, M, Boks, M, Borglum, AD, Bramon, E, Breen, G, Brown, MA, Bruggeman, R, Buccola, NG, Buckner, RL, Budde, M, Bulik-Sullivan, B, Bumpstead, SJ, Bunney, W, Burmeister, M, Buxbaum, JD, Bybjerg-Grauholm, J, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Casas, JP, Casas, M, Catts, SV, Cervantes, P, Chambert, KD, Chan, RCK, Chen, EYH, Chen, RYL, Cheng, W, Cheung, EFC, Chong, SA, Clarke, TK, Cloninger, CR, Cohen, D, Cohen, N, Coleman, JRI, Collier, DA, Cormican, P, Coryell, W, Craddock, N, Craig, DW, Ruderfer, DM, Ripke, S, McQuillin, A, Boocock, J, Stahl, EA, Pavlides, JMW, Mullins, N, Charney, AW, Ori, APS, Loohuis, LMO, Domenici, E, Di Florio, A, Papiol, S, Kalman, JL, Trubetskoy, V, Adolfsson, R, Agartz, I, Agerbo, E, Akil, H, Albani, D, Albus, M, Alda, M, Alexander, M, Alliey-Rodriguez, N, Als, TD, Amin, F, Anjorin, A, Arranz, MJ, Awasthi, S, Bacanu, SA, Badner, JA, Baekvad-Hansen, M, Bakker, S, Band, G, Barchas, JD, Barroso, I, Bass, N, Bauer, M, Baune, BT, Begemann, M, Bellenguez, C, Belliveau, RA, Bellivier, F, Bender, S, Bene, J, Bergen, SE, Berrettini, WH, Bevilacqua, E, Biernacka, JM, Bigdeli, TB, Black, DW, Blackburn, H, Blackwell, JM, Blackwood, DHR, Pedersen, CB, Boehnke, M, Boks, M, Borglum, AD, Bramon, E, Breen, G, Brown, MA, Bruggeman, R, Buccola, NG, Buckner, RL, Budde, M, Bulik-Sullivan, B, Bumpstead, SJ, Bunney, W, Burmeister, M, Buxbaum, JD, Bybjerg-Grauholm, J, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Casas, JP, Casas, M, Catts, SV, Cervantes, P, Chambert, KD, Chan, RCK, Chen, EYH, Chen, RYL, Cheng, W, Cheung, EFC, Chong, SA, Clarke, TK, Cloninger, CR, Cohen, D, Cohen, N, Coleman, JRI, Collier, DA, Cormican, P, Coryell, W, Craddock, N, and Craig, DW
Abstract: Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.
Published: 2018

30. THE NEURAPRO STUDY: ADHERENCE TO STUDY MEDICATION

Author: Schloegelhofer, M, McGorry, PD, Nelson, B, Markulev, C, Yuen, HP, Schaefer, M, Mossaheb, N, Smesny, S, Hickie, IB, Berger, G, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Thompson, A, Yung, Alison, Amminger, GP, Schloegelhofer, M, McGorry, PD, Nelson, B, Markulev, C, Yuen, HP, Schaefer, M, Mossaheb, N, Smesny, S, Hickie, IB, Berger, G, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Roessler, A, Verma, S, Thompson, A, Yung, Alison, and Amminger, GP
Published: 2018

31. NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.

Author: Nelson, B, Amminger, GP, Yuen, HP, Markulev, C, Lavoie, S, Schäfer, MR, Hartmann, JA, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, G, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR, McGorry, PD, Nelson, B, Amminger, GP, Yuen, HP, Markulev, C, Lavoie, S, Schäfer, MR, Hartmann, JA, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, G, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR, and McGorry, PD
Abstract: This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.
Published: 2018

32. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author: Ni, G, Gratten, J, Wray, NR, Lee, SH, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Haan, L de, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Juliá, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JLC, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, van Os, JV, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, Xuebin, Zimprich, F, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, Daniëlle, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Clair, DS, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, O'Donovan, MC, Ni, G, Gratten, J, Wray, NR, Lee, SH, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Haan, L de, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Juliá, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JLC, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, van Os, JV, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, Xuebin, Zimprich, F, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, Daniëlle, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Clair, DS, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, and O'Donovan, MC
Published: 2018

33. The Effect of Paternal Age on Relapse in First-Episode Schizophrenia

Author: Chang, WC, Law, CW, Hui, CLM, Li, YK, Chiu, CPY, Chen, EYH, Sham, PC, Lee, HME, and Chan, KW
Abstract: published_or_final_version
Published: 2015

34. Biological insights from 108 schizophrenia-associated genetic loci

Author: Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, and Escott-Price, V
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. © 2014 Macmillan Publishers Limited. All rights reserved.
Published: 2014
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35. Social anxiety and ideas of reference in early psychosis

Author: Chiu, CPY, Chen, EYH, Wong, GHY, and Hui, CLM
Abstract: This journal suppl. contain abstracts of the 12th International Congress on Schizophrenia Research (ICOSR), Session - 2. 2. Phenomenology, An increased prevalence of social anxiety disorder is observed in patients with psychosis (16%–38%, compared with 13% in the general population). Despite important treatment implications, previous attempts in understanding the comorbidity have been inconclusive. This study aims to explore the relationship between social anxiety and other psychopathological characteristics in psychotic disorders, with a conceptually driven focus on the possible linkage between social anxiety and the subthreshold symptom ideas of reference. A consecutive sample of 137 outpatients with early psychosis was assessed for social anxiety using the Liebowitz Social Anxiety Scale (LSAS), and for ideas of reference using a new instrument Ideas of Reference Interview Schedule (IRIS). Positive symptoms, negative symptoms, depression and insight were measured using the Scale for the Assessment of Positive Symptoms in Schizophrenia (SAPS), the Scale for the Assessment of Negative Symptoms in Schizophrenia (SANS), Calgary Depression Scale for Schizophrenia (CDSS) and the Scale to Assess Unawareness of Illness (SUMD). To identify potential explanatory variables for social anxiety, univariate analyses were first carried out between LSAS and age, sex and all symptom subscales. Variables that displayed simple correlation with LSAS (based on a lax criterion of P < .1) were then entered as independent variables into a stepwise multiple regression analysis to determine the symptoms specifically correlated with LSAS. Results suggested a three-factor model, with IRIS included as the strongest explanatory factor, while avolition and blunting were also related (adjust R2 = 0.18; P = .00). The association observed between social anxiety and negative symptoms is consistent with previous findings. This is the first study to demonstrate that a proportion of social anxiety covaries with ideas of reference. The nature of their relationship and the extent to which ideas of reference may explain for the excess of social anxiety prevalence in early psychosis need to be further investigated., link_to_OA_fulltext
Published: 2009

36. A case-controlled study on the outcome of an early intervention programme for psychosis (EASY)

Author: Tso, S, Yew, CWS, Law, CW, Chan, K, Hung, SF, Chung, D, Tay, M, Yip, KC, Lam, MLM, Chiu, CPY, Wong, GHY, Chen, EYH, Hui, CLM, and Tang, YMJ
Abstract: This journal suppl. entitled: Abstracts for the 12th International Congress on Schizophrenia Research (ICOSR), In an attempt to improve the outcome for psychotic disorders, the EASY (Early Assessment Service for Young People with Psychosis) programme was launched in Hong Kong in 2001. Being one of the first in Asia, it comprised of two major components, namely early detection and critical period intervention. Comparison was made with a matched historical control group under standard care where the first psychotic episode was usually managed under in-patient care, followed by relatively sparse outpatient visits with little psychosocial support. The EASY service provides specialized multidisciplinary team to offer a comprehensive package of intervention targeting the specific needs of patients and their carers at this stage of the disorder. It adopts a case-management approach and assertively follows first-episode patients for 2 years after the initial episode. Results at three years showed that EI patients had fewer days in hospital, better functional outcome, lower likelihood of disengagement from service, and less aggressive behaviour, completed suicides or suicide attempts. No significant difference was found for relapses and the duration of untreated psychosis (DUP) suggesting that in Hong Kong, the improved outcome was not mediated by these two variables. The present study suggests that early psychosis programme in Hong Kong is successful in improving the 3-year outcome of psychotic disorders. The effect appears to be attributable to improved intervention rather than to a reduction of DUP, relapses or atypical medication., link_to_OA_fulltext
Published: 2009

37. Gender Differences of Persons with Schizophrenia in Rural China

Author: Ran, MS, Chan, CLW, Chen, EYH, Li, L, Lin, FR, Tang, CP, Mao, WJ, Conwell, Y, and Hu, SH
Abstract: The gender characteristics of persons with schizophrenia in rural community are still unknown. The goal of this study is to explore the gender differences of persons with schizophrenia in a longitudinal study in rural China. METHODS: A 10-year follow-up investigation among a 1994 cohort (n = 510) of patients with schizophrenia was conducted in Xinjin County, Chengdu, China. All the patients and their informants (100%) were followed up in 2004 using Patients Follow-up Scale (PFS). RESULTS: The results indicated that male patients had significantly higher level of education and rates of unmarried and divorced than females. Female patients had significantly more family members. Male patients had significantly worse social function. The rate of homelessness was significantly higher in male than female (Log-rank test, v2 = 4.00, P < .05). The mortality rate was significantly higher in male {2913 per 100 000 person-years (95% CI = 2174–3652)} than female patients {1661 per 100 000 person-years (95% CI = 1150–2172)} (Hazard ratio 2.0, 95% CI = 1.3–3.2, P < .005). Although there were no significant differences of suicidal attempts between male and female patients, the suicide rate was significantly higher in male {753 per 100 000 person-years (95% CI = 373–1133)} than female patients {249 per 100 000 person-years (95% CI = 50–448)} (Hazard ratio 3.1, 95% CI = 1.2–8.0, P < .05). CONCLUSIONS: The outcome of male patients is worse than females in rural China. Higher mortality and suicide in male than female patients may contribute to the higher prevalence of schizophrenia in women than in men in China. Specific intervention strategies for improving the outcome of the illness should be developed for male and female patients with schizophrenia. Acknowledgments: This work was supported in part by GRIP 1 R01 TW007260–01 (M.S. Ran, PI) from the Fogarty International Center of NIH., link_to_OA_fulltext
Published: 2009

38. Relapse prevention in first-episode psychosis patients with stable maintenance medication for at least one year

Author: Hui, CLM, Chen, EYH, Chung, D, Yau, T, Chan, K, Tso, S, Chiu, CPY, Honer, WG, Hung, SF, Wong, YC, Chan, KT, Pang, E, Law, CW, and Lam, MLM
Abstract: 22. 22. Therapeutics: Treatment Trials, s for the 12th International Congress on Schizophrenia Research (ICOSR), Clinically there is a strong expectation from first-episode psychosis patients and their carers to discontinue with maintenance medication after a period of remission. However, there is so far no consensus regarding how long maintenance medication should be continued. The current study aims to assess whether this point in time is reached after at least 1 year of maintenance medication. Following a first-episode of schizophrenia and non-affective psychosis (DSM-IV), patients who were remitted well and on maintenance medication for at least 12 months were randomized to receive either maintenance medication (quetiapine 400mg/day) or placebo. Relapse was defined as the re-emergence of positive symptoms. In the overall sample of 178, 83 patients relapsed during the study. Fewer patients relapsed in the quetiapine maintenance group (27 of 89, 30%) compared with the placebo group (56 of 89, 63%). The Kaplan-Meier estimate of the proportion of relapse at 11 months after randomization was 41 percent (95% CI, 29 to 53%) in the quetiapine maintenance group and 76 percent (95% CI, 66 to 86%) in the placebo group (log-rank test, v2 = 15.65, P < .001). New data for relapse risks in remitted first-episode psychosis patients is provided. The risk of relapse after medication discontinuation is still substantial after receiving maintenance medication for a mean of 22 months following first-episode psychosis. Supported by investigator initiated trial award from AstraZeneca and the Research Grants Council Hong Kong (Project number: 765505)., link_to_OA_fulltext
Published: 2009

39. Relapse predictors for discontinuing and continuing maintenance medication in remitted first-episode psychosis patients

Author: Chiu, CPY, Honer, WG, Lam, MLM, Hung, SF, Yao, TJ, Chan, K, Chen, EYH, Hui, CLM, Pang, EPF, Tso, S, Chung, DWS, Law, CW, Chan, KT, and Wong, YC
Abstract: This journal suppl. entitled: Abstracts for the 12th International Congress on Schizophrenia Research (ICOSR), After a first-episode psychosis, patients inevitably face a clinical dilemma regarding whether to continue with maintenance medication after a period of remission. This decision has to be weighed against the long-term medication side effects and the risk of relapse. In this study, we aim to identify potential predictors for relapse among patients who have continued with maintenance medication, as well as those who have discontinued with maintenance medication. This is a double-blind randomized placebo-controlled study. Patients who were remitted from a first-episode of schizophrenia or non-affective psychosis (DSM-IV) and had remained well on maintenance medication for at least 1 year were recruited into this study. Eligible patients were randomized to either quetiapine (400mg/d) or placebo for 12 months to detect a relapse. Relapse was defined as re-emergence of definitive positive symptoms. Baseline clinical and cognitive variables were measured as potential predictors for relapse. Univariate and multivariate Cox-proportional hazards models were applied to analyze significant predictors in the maintenance medication and the placebo groups. A total of 178 patients were recruited. In the placebo group, significant multivariate relapse predictors were smoking (relative risk 4.317, 95% CI = 1.012–18.417), negative symptoms (relative risk 1.030, 95% CI = 1.008–1.053) and verbal fluency (relative risk 0.880, 95% CI = 0.807–0.960). In the medication group, significant multivariate relapse predictors were pre-morbid functioning (interest) (relative risk 1.641, 95% CI = 1.215–2.216), PANSS (general psychopathology) (relative risk 1.548, 95% CI = 1.089–2.200), logical memory at immediate recall (relative risk 0.879, 95% CI = 0.782–0.988) and neurological soft signs (disinhibition) (relative risk 3.423, 95% CI = 1.585–7.390). Importantly, predictors identified in the two groups help provide information about the characteristics of the patients who are more prone to relapse. Future intervention strategies for relapse prevention can be based on the current findings., link_to_OA_fulltext
Published: 2009

40. The first three years of pharmacotherapy in patients with psychotic disorders: a comparison between the early intervention programme and standard care service in Hong Kong

Author: Tang, JYM, Hui, CLM, Chen, EYH, Lam, MLM, Chan, K, Hung, SF, Law, CW, Tso, S, Tay, M, Chiu, CPY, Yew, C, Wong, GHY, Chung, DWS, and Yip, KC
Abstract: Session - 9. 9. Health Economics and Services Research, s for the 12th International Congress on Schizophrenia Research (ICOSR), This naturalistic study reviews the use of antipsychotics in patients with psychotic disorders in the first three years of psychiatric treatment. This historical-controlled study included 700 patients first presented to the local early intervention programme (EI) from 2001 to 2003, and 700 patients first presented to standard care service (SC) from 1998 to 2001. The data were systematically extracted from medical records according to operationalized definitions. In the EI group, 22.2% of cases were prescribed atypical antipsychotics as the initial pharmacotherapy, which increased to 59.4% and 58.7% in the first and second switches of antipsychotics respectively. Respective statistics in the SC group (6.3%, 19.5% and 23.4%, all p-value, link_to_OA_fulltext
Published: 2009

41. Cognitive correlates of semantic language disorder in first-episode schizophrenia

Author: Chiu, CPY, Chen, EYH, Hui, CLM, and Law, CW
Abstract: Introduction: Language disorder in schizophrenia is commonly measured using instruments such as the Thought, Language and Communicative disorder rating scale (TLC). However, the TLC score represent an aggregate measure of abnormalities at different linguistic levels. The Clinical Language Disorder Rating Scale (CLANG) was developed (Chen et al., 1996) based on psycholinguistic levels. Factor analysis yielded three distinct levels of abnormalities: semantic, poverty and general. The diagnostic significance for CLANG has been suggested (Ceccherini-Nelli and Crow, 2003). The present study aimed to explore the relationship between language disorder and cognition in a sample of first episode schizophrenic patients. Methods: 45 first-episode schizophrenic patients (DSM-IV) in Hong Kong, were recruited at the time of their illness presentation (drug naïve). The mean age was 25 sd 8.9), mean education was 11.4 years (sd 2.57). Cognitive measures included IQ, verbal fluency, letter number span, visual production, stroop, logical memory, trail making, six element test and Wisconsin Card Sorting Test (WCST). Results: Stepwise linear regression analyses were computed for each of the CLANG dimensions. “Semantic” dysfunctions are associated with trail making B (p, link_to_subscribed_fulltext, The 2007 International Congress on Schizophrenia Research, Colorado Springs, Colorado, 27-28 March 2007. In Schizophrenia Bulletin, 2007, v. 33 n. 2, p. 214
Published: 2007

42. A translational research approach to poor treatment response in patients with schizophrenia: clozapine--antipsychotic polypharmacy.

Author: Honer WG, Procyshyn RM, Chen EYH, MacEwan GW, and Barr AM
Published: 2009

43. What does recovery from schizophrenia mean? Perceptions of long-term patients.

Author: Ng RMK, Pearson V, Lam M, Law CW, Chiu CPY, and Chen EYH
Abstract: Background: The study investigated the meaning of recovery to eight people with chronic schizophrenia.Method: A qualitative methodology was used based on a 3-hour focus group. The material was transcribed and analysed into 18 subcategories and 4 categories; namely recovery as a multi-dimensional construct, the relationship of medication to recovery, a sense of hopelessness and helplessness about recovery, factors that promoted recovery.Discussion: Respondents believed that full recovery could not be said to have been achieved until they stopped medication and had a steady job. The support and care of family and friends were also vital, although sometimes problematic. Independent living has a different meaning in Chinese culture.Conclusions: Further research directions are suggested as well as ways to change attitudes to the inclusion of medication in recovery. [ABSTRACT FROM AUTHOR]
Published: 2008

44. Changes in serum lipids, independent of weight, are associated with changes in symptoms during long-term clozapine treatment.

Author: Procyshyn RM, Wsan KM, Thornton AE, Barr AM, Chen EYH, Pomarol-Clotet E, Stip E, Williams R, MacEwan W, Birmingham CL, Honer WG, and Clozapine and Risperidone Enhancement Study Group
Abstract: OBJECTIVE: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. METHODS: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. RESULTS: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. CONCLUSION: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity. [ABSTRACT FROM AUTHOR]
Published: 2007

45. Efficacy of a brief intervention for carers of people with first-episode psychosis: a waiting list controlled study.

Author: So HW, Chen EYH, Chan RCK, Wong CW, Hung SF, Chung DWS, Ng SM, and Chan CLW
Abstract: Objectives: While family psycho-education for schizophrenia is well-supported, the efficacy of family intervention for first-episode psychosis is less studied. This waiting list controlled study set out to evaluate the effectiveness of a 6-week intervention for carers of people with first-episode psychosis. Participants and Methods: Carers were randomised into experimental or waiting list categories. Study 1 compared various outcome measures in the 2 categories. Study 2 evaluated the treatment effects. Results: After the intervention, carers showed increased knowledge about psychosis and a reduction in negative ways of coping. The improvement in knowledge was maintained at 6-month follow-up, and trends towards improved caregiving burden and coping were also evident.Conclusions: A brief intervention programme can be effective in improving important variables such as knowledge, coping, and caregiving burden. The implications for selecting 'core components' for an effective intervention were discussed. [ABSTRACT FROM AUTHOR]
Published: 2006

46. The role of knowledge and motivation in symptom identification accuracy among schizophrenic patients: application of signal detection theory.

Author: Wong AWS, Chiu C, Mok JWY, Wong JGW, and Chen EYH
Abstract: Objective. Many people with schizophrenia have poor awareness of their symptoms, a problem that may result from lack of knowledge about their illness and/or unwillingness to acknowledge it. The present study assessed the joint influence of lack of knowledge and motivated denial in schizophrenic patients' low symptom awareness. Method. Schizophrenic patients (N = 85) and normal control participants (N = 35) identified psychotic symptoms and general stress symptoms in a symptom checklist. The signal detection theory was applied to assess levels of sensitivity (which would be knowledge-mediated) and judgment biases (which would probably be motivated). Results. Compared with normal control participants, schizophrenic patients had lower sensitivity and greater aversion to classify a symptom as a psychotic symptom. Conclusions. These findings suggest that both lack of knowledge and motivated denial are involved in schizophrenic patients' low symptom awareness. [ABSTRACT FROM AUTHOR]
Published: 2006
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47. Suicide in Hong Kong: a case-control psychological autopsy study.

Author: Chen EYH, Chan WSC, Wong PWC, Chan SSM, Chan CLW, Law YW, Beh PSL, Chan KK, Cheng JWY, Liu KY, and Yip PSF
Abstract: Background. The relative contribution of psychosocial and clinical risk factors to suicide among Chinese populations is an important issue. In Hong Kong, this issue requires vigorous examination in light of a 50% increase in suicide rate between 1997 and 2003.Method. Using a case-control psychological autopsy method, 150 suicide deceased were compared with 150 living controls matched by age and gender. Semi-structured interviews were conducted with the next-of-kin of the subjects. Data were collected on a wide range of potential risk and protective factors, including demographic, life event, clinical and psychological variables. The relative contribution of these factors towards suicide was examined in a multiple logistic regression model.Results. Six factors were found to significantly and independently contribute to suicide: unemployment, indebtedness, being single, social support, psychiatric illness, and history of past attempts.Conclusions. Both psychosocial and clinical factors are important in suicides in Hong Kong. They seem to have mediated suicide risk independently. In addition, socio-economic adversities seem to have played a relatively important role in the increasing suicide rate in Hong Kong. [ABSTRACT FROM AUTHOR]
Published: 2006
Full Text: View/download PDF

48. Clozapine alone versus clozapine and risperidone with refractory schizophrenia.

Author: Honer WG, Thornton AE, Chen EYH, Chan RCK, Wong JOY, Bergmann A, Falkai P, Pomarol-Clotet E, McKenna PJ, Stip E, Williams R, MacEwan W, Wasan K, Procyshyn R, and Clozapine and Risperidone Enhancement Study Group
Published: 2006

49. Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia

Author: Pardiñas, Antonio F., Smart, Sophie E., Corvin, Aiden, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Gershon, Elliot S., Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Fanous, Ayman H., Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, Haan, Lieuwe de, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Frank, Josef, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Kelly, Brian, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, McQuillin, Andrew, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Melle, Ingrid, Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Mortensen, Preben B., Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Mowry, Bryan J., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Pato, Carlos N., Morris, Derek W., Mors, Ole, Murphy, Kieran C., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Periyasamy, Sathish, Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O’Callaghan, Eadbhard, O’Dushlaine, Colm, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Os, Jim Van, Willcocks, Isabella R., Rietschel, Marcella, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Rujescu, Dan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Simonsen, Carmen, Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., St Clair, David, Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Tooney, Paul, Spencer, Chris C. A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T. Scott, Subramaniam, Mythily, Wu, Jing Qin, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Andreassen, Ole A., Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H. M., Kowalec, Kaarina, Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Blackwood, Douglas H. R., Sullivan, Patrick F., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Murray, Robin M., Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Holmans, Peter A., Owen, Michael J., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., Moran, Jennifer L., Nöthen, Markus M., Ophoff, Roel A., Palotie, Aarno, Petryshen, Tracey L., MacCabe, James H., Posthuma, Danielle, Riley, Brien P., Sham, Pak C., Sklar, Pamela, Clair, David St, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Agbedjro, Deborah, O’Donovan, Michael C., Stahl, Daniel, Kapur, Shitij, Millgate, Edward, Kepinska, Adrianna, Kravariti, Eugenia, Ajnakina, Olesya, Alameda, Luis, Barnes, Thomas R. E., Berardi, Domenico, Bonora, Elena, Walters, James T. R., Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D’Andrea, Giuseppe, Demjaha, Arsime, Do, Kim Q., Doody, Gillian A., Eap, Chin B., Ferchiou, Aziz, Ripke, Stephan, Di Forti, Marta, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen M., Kassoumeri, Laura, Khadimallah, Inès, Lastrina, Ornella, Muratori, Roberto, Noyan, Handan, Neale, Benjamin M., O’Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Schürhoff, Franck, Španiel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Farh, Kai-How, Vázquez-Bourgon, Javier, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Dennison, Charlotte A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A ., Lynham, Amy J., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Legge, Sophie E., Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C. K., Chen, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Baune, Bernhard T., Cheung, Eric F. C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Bigdeli, Tim B., Davis, Kenneth L., Degenhardt, Franziska, Favero, Jurgen Del, DeLisi, Lynn E., Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Cairns, Murray J., Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Farrell, Martilias S., Franke, Lude, Freedman, Robert, Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances (STRATA) Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC), Ripke, S., Neale, B.M., Farh, K.H., Lee, P., Bulik-Sullivan, B., Collier, D.A., Huang, H., Pers, T.H., Agartz, I., Agerbo, E., Albus, M., Alexander, M., Amin, F., Bacanu, S.A., Begemann, M., Belliveau, R.A., Bene, J., Bergen, S.E., Bevilacqua, E., Black, D.W., Bruggeman, R., Buccola, N.G., Buckner, R.L., Byerley, W., Cahn, W., Cai, G., Campion, D., Cantor, R.M., Carr, V.J., Carrera, N., Catts, S.V., Chambert, K.D., Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W., Cheung, EFC, Chong, S.A., Cloninger, C.R., Cohen, D., Cohen, N., Cormican, P., Craddock, N., Crowley, J.J., Curtis, D., Davidson, M., Davis, K.L., Degenhardt, F., Favero, J.D., DeLisi, L.E., Demontis, D., Dikeos, D., Dinan, T., Djurovic, S., Donohoe, G., Drapeau, E., Duan, J., Dudbridge, F., Durmishi, N., Eichhammer, P., Eriksson, J., Escott-Price, V., Essioux, L., Farrell, M.S., Franke, L., Freedman, R., Freimer, N.B., Friedl, M., Friedman, J.I., Fromer, M., Genovese, G., Georgieva, L., Gershon, E.S., Giegling, I., Giusti-Rodríguez, P., Godard, S., Goldstein, J.I., Golimbet, V., Gopal, S., Gratten, J., Haan, L., Hammer, C., Hamshere, M.L., Hansen, M., Hansen, T., Haroutunian, V., Hartmann, A.M., Henskens, F.A., Herms, S., Hirschhorn, J.N., Hoffmann, P., Hofman, A., Hollegaard, M.V., Hougaard, D.M., Ikeda, M., Joa, I., Julià, A., Kahn, R.S., Kalaydjieva, L., Karachanak-Yankova, S., Karjalainen, J., Kavanagh, D., Keller, M.C., Kennedy, J.L., Khrunin, A., Kim, Y., Klovins, J., Knowles, J.A., Konte, B., Kucinskas, V., Kucinskiene, Z.A., Kuzelova-Ptackova, H., Kähler, A.K., Laurent, C., Keong, JLC, Lee, S.H., Lerer, B., Li, M., Li, T., Liang, K.Y., Lieberman, J., Limborska, S., Loughland, C.M., Lubinski, J., Lönnqvist, J., Macek, M., Magnusson, PKE, Maher, B.S., Maier, W., Mallet, J., Marsal, S., Mattheisen, M., Mattingsdal, M., McCarley, R.W., McDonald, C., McIntosh, A.M., Meier, S., Meijer, C.J., Melegh, B., Melle, I., Mesholam-Gately, R.I., Metspalu, A., Michie, P.T., Milani, L., Milanova, V., Mokrab, Y., Morris, D.W., Mors, O., Murphy, K.C., Myin-Germeys, I., Müller-Myhsok, B., Nelis, M., Nenadic, I., Nertney, D.A., Nestadt, G., Nicodemus, K.K., Nikitina-Zake, L., Nisenbaum, L., Nordin, A., O'Callaghan, E., O'Dushlaine, C., O'Neill, F.A., Oh, S.Y., Olincy, A., Olsen, L., Os, J.V., Pantelis, C., Papadimitriou, G.N., Papiol, S., Parkhomenko, E., Pato, M.T., Paunio, T., Pejovic-Milovancevic, M., Perkins, D.O., Pietiläinen, O., Pimm, J., Pocklington, A.J., Powell, J., Price, A., Pulver, A.E., Purcell, S.M., Quested, D., Rasmussen, H.B., Reichenberg, A., Reimers, M.A., Richards, A.L., Roffman, J.L., Roussos, P., Ruderfer, D.M., Salomaa, V., Sanders, A.R., Schall, U., Schubert, C.R., Schulze, T.G., Schwab, S.G., Scolnick, E.M., Scott, R.J., Seidman, L.J., Shi, J., Sigurdsson, E., Silagadze, T., Silverman, J.M., Sim, K., Slominsky, P., Smoller, J.W., So, H.C., Spencer, CCA, Stahl, E.A., Stefansson, H., Steinberg, S., Stogmann, E., Straub, R.E., Strengman, E., Strohmaier, J., Stroup, T.S., Subramaniam, M., Suvisaari, J., Svrakic, D.M., Szatkiewicz, J.P., Söderman, E., Thirumalai, S., Toncheva, D., Tosato, S., Veijola, J., Waddington, J., Walsh, D., Wang, D., Wang, Q., Webb, B.T., Weiser, M., Wildenauer, D.B., Williams, N.M., Williams, S., Witt, S.H., Wolen, A.R., Wong, EHM, Wormley, B.K., Xi, H.S., Zai, C.C., Zheng, X., Zimprich, F., Wray, N.R., Stefansson, K., Visscher, P.M., Adolfsson, R., Blackwood, DHR, Bramon, E., Buxbaum, J.D., Børglum, A.D., Cichon, S., Darvasi, A., Domenici, E., Ehrenreich, H., Esko, T., Gejman, P.V., Gill, M., Gurling, H., Hultman, C.M., Iwata, N., Jablensky, A.V., Jönsson, E.G., Kendler, K.S., Kirov, G., Knight, J., Lencz, T., Levinson, D.F., Li, Q.S., Liu, J., Malhotra, A.K., McCarroll, S.A., Moran, J.L., Mortensen, P.B., Nöthen, M.M., Ophoff, R.A., Palotie, A., Petryshen, T.L., Posthuma, D., Riley, B.P., Sham, P.C., Sklar, P., Clair, D.S., Weinberger, D.R., Wendland, J.R., Werge, T., Daly, M.J., Agbedjro, D., Stahl, D., Kapur, S., Millgate, E., Kepinska, A., Kravariti, E., Medical Research Council (UK), Cardiff University, Welsh Government, Health and Care Research Wales, European Commission, Academy of Medical Sciences (UK), Research Council of Norway, K. G. Jebsen Centres for Medical Research, National Institute for Health Research (UK), University College London, Government of Canada, University of Manitoba, Swedish Research Council, National Institute of Mental Health (US), Kings College London, Public Health Agency (Northern Ireland), The Psychiatry Research Trust, Maudsley Charity, Swiss National Science Foundation, Fondation Alamaya, Ministry of Health of the Czech Republic, Instituto de Salud Carlos III, Plan Nacional sobre Drogas (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Wellcome Trust, and Universidad de Cantabria
Subjects: Male, endocrine system, Multifactorial Inheritance, animal structures, Psychiatry and Behavioral Health, Online First, Humans, Genetic Predisposition to Disease, ddc:610, Neurogenetics, Medicinsk genetik, Original Investigation, Research, Schizophrenia Sprectum and Other Psychotic Disorders, Featured, Genetics and genomics, Psychiatry and Mental health, Neurology, Psychotic Disorders, Schizophrenia, Female, Medical Genetics, hormones, hormone substitutes, and hormone antagonists, Comments, Genome-Wide Association Study
Abstract: [Importance] About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts., [Objective] To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples., [Design, Setting, and Participants] Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G])., [Main Outcomes and Measures] GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition., [Results] The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04)., [Conclusions and Relevance] In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance., This work was supported by Medical Research Council Centre grant MR/L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union’s Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union’s Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L011794/1), which funded the research and supported Drs Pardiñas, Smart, Kassoumeri, Murray, Walters, and MacCabe. Dr Smart was supported by a Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital National Health Service Foundation Trust. The AESOP (US) cohort was funded by the UK Medical Research Council (grant G0500817). The Belfast (UK) cohort was funded by the Research and Development Office of Northern Ireland. The Bologna (Italy) cohort was funded by the European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Genetics and Psychosis project (London, UK) cohort was funded by the UK National Institute of Health Research Specialist Biomedical Research Centre for Mental Health, South London and the Maudsley National Health Service Mental Health Foundation Trust (SLAM) and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London; Psychiatry Research Trust; Maudsley Charity Research Fund; and the European Community’s Seventh Framework program (HEALTH-F2-2009-241909, project EU-GEI). The Lausanne (Switzerland) cohort was funded by the Swiss National Science Foundation (grants 320030_135736/1, 320030-120686, 324730-144064, 320030-173211, and 171804); the National Center of Competence in Research Synaptic Bases of Mental Diseases from the Swiss National Science Foundation (grant 51AU40_125759); and Fondation Alamaya. The Oslo (Norway) cohort was funded by the Research Council of Norway (grant 223273/F50, under the Centers of Excellence funding scheme, 300309, 283798) and the South-Eastern Norway Regional Health Authority (grants 2006233, 2006258, 2011085, 2014102, 2015088, and 2017-112). The Paris (France) cohort was funded by European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Prague (Czech Republic) cohort was funded by the Ministry of Health of the Czech Republic (grant NU20-04-00393). The Santander (Spain) cohort was funded by the following grants to Dr Crespo-Facorro: Instituto de Salud Carlos III (grants FIS00/3095, PI020499, PI050427, and PI060507), Plan Nacional de Drogas Research (grant 2005-Orden sco/3246/2004), SENY Fundatio Research (grant 2005-0308007), Fundacion Marques de Valdecilla (grant A/02/07, API07/011) and Ministry of Economy and Competitiveness and the European Fund for Regional Development (grants SAF2016-76046-R and SAF2013-46292-R). The West London (UK) cohort was funded by The Wellcome Trust (grants 042025, 052247, and 064607).
Published: 2022
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50. A three-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: relationship with relapse and neurocognitive function.

Author: Chan, KKS, Hui, CLM, Lam, MML, Tang, JYM, Wong, GHY, Chan, SKW, and Chen, EYH
Abstract: Objective: To examine the spontaneous blink rate over a 3-year period and its clinical and cognitive correlates among patients with first-episode schizophrenia. Methods: This study prospectively followed 93 patients with first-episode schizophrenia, schizophreniform and schizoaffective disorders for 3 years. Patients were longitudinally assessed for blink rate, their positive and negative symptoms, and a range of cognitive features including verbal fluency, verbal memory, visual memory, and the Wisconsin Card Sorting Test performance. Results: When compared with a matched control group, there was a significantly higher blink rate at their 3-year follow-up but not at initial presentation. The increase in blink rate over time correlated positively with the number of relapses. It also correlated with logical memory, verbal fluency, categories completed, and perseverative errors in the Wisconsin Card Sorting Test. The increased blink rate also correlated with pre-morbid schizoid and schizotypal traits. All these correlations were statistically significant. Conclusion: The change in the blink rate over time may reflect underlying involvement of the dopaminergic system in mediating relapse and cognitive functions. [ABSTRACT FROM AUTHOR]
Published: 2010

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