Skip to main content Accessibility help

Predicting psychosis risk using a specific measure of cognitive control: a 12-month longitudinal study

  • Joyce Y. Guo (a1) (a2), Tara A. Niendam (a1), Andrea M. Auther (a3), Ricardo E. Carrión (a3), Barbara A. Cornblatt (a3), J. Daniel Ragland (a1), Steven Adelsheim (a4), Roderick Calkins (a5), Tamara G. Sale (a6), Stephan F. Taylor (a7), William R. McFarlane (a6) (a8) and Cameron S. Carter (a1) (a2)...



Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up.


Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models.


Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups.


These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.


Corresponding author

Author for correspondence: Joyce Y. Guo, E-mail:


Hide All

Co-first Joyce Y. Guo & Tara A. Niendam provided equal contributions to this manuscript.



Hide All
Addington, J, Liu, L, Buchy, L, Cadenhead, KS, Cannon, TD, Cornblatt, BA, Perkins, DO, Seidman, LJ, Tsuang, MT, Walker, EF, Woods, SW, Bearden, CE, Mathalon, DH and Mcglashan, TH (2015) North American prodrome Longitudinal Study (NAPLS 2): the prodromal symptoms. The Journal of Nervous and Mental Disease 203, 328335.
Allen, P, Luigjes, J, Howes, OD, Egerton, A, Hirao, K, Valli, I, Kambeitz, J, Fusar-Poli, P, Broome, M and Mcguire, P (2012) Transition to psychosis associated With prefrontal and subcortical dysfunction in ultra high-risk individuals. Schizophrenia Bulletin 38, 12681276.
American Psychological Association Practice Organization (2014) Distinguishing between screening and assessment for mental and behavioral health problems: A statement from an American Psychological Association Practice Organization work group on screening and psychological assessment. [Online]. Available at (Accessed).
Bechdolf, A, Wagner, M, Ruhrmann, S, Harrigan, S, Putzfeld, V, Pukrop, R, Brockhaus-Dumke, A, Berning, J, Janssen, B, Decker, P, Bottlender, R, Maurer, K, Möller, HJ, Gaebel, W, Häfner, H, Maier, W and Klosterkötter, J (2012) Preventing progression to first-episode psychosis in early initial prodromal states. British Journal of Psychiatry 200, 2229.
Birur, B, Kraguljac, NV, Shelton, RC and Lahti, AC (2017) Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder – a systematic review of the magnetic resonance neuroimaging literature. Nature Partner Journals Schizophrenia 3, 15.
Bora, E and Murray, RM (2014) Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis? Schizophrenia Bulletin 40, 744755.
Bora, E, Yucel, M and Pantelis, C (2010) Cognitive impairment in schizophrenia and affective psychoses: implications for DSM-V criteria and beyond. Schizophrenia Bulletin 36, 3642.
Braver, TS, Barch, DM, Keys, BA, Carter, CS, Cohen, JD, Kaye, JA, Janowsky, JS, Taylor, SF, Yesavage, JA, Mumenthaler, MS, Jagust, WJ and Reed, BR (2001) Context processing in older adults: Evidence for a theory relating cognitive control to neurobiology in healthy aging. Journal of Experimental Psychology: General 130, 746763.
Cannon, TD, Cadenhead, K, Cornblatt, B, Woods, SW, Addington, J, Walker, E, Seidman, LJ, Perkins, D, Tsuang, M, Mcglashan, T and Heinssen, R (2008) Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Archives of General Psychiatry 65, 2837.
Cannon, TD, Yu, C, Addington, J, Bearden, CE, Cadenhead, KS, Cornblatt, BA, Heinssen, R, Jeffries, CD, Mathalon, DH, Mcglashan, TH, Perkins, DO, Seidman, LJ, Tsuang, MT, Walker, EF, Woods, SW and Kattan, M (2016) An individualized risk calculator for research in prodromal psychosis. The American Journal of Psychiatry 173, 980988.
Carrión, RE, Cornblatt, BA, Burton, CZ, Tso, IF, Auther, A, Adelsheim, S, Calkins, R, Carter, CS, Niendam, T, Taylor, SF and Mcfarlane, WR (2016) Personalized prediction of psychosis: external validation of the NAPLS2 psychosis risk calculator with the EDIPPP project. The American Journal of Psychiatry 173, 989996.
Carter, CS and Barch, DM (2007) Cognitive neuroscience-based approaches to measuring and improving treatment effects on cognition in schizophrenia: the CNTRICS initiative. Schizophrenia Bulletin 33, 11311137.
Cornblatt, BA, Auther, AM, Niendam, T, Smith, CW, Zinberg, J, Bearden, CE and Cannon, TD (2007) Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia. Schizophrenia Bulletin 33, 688702.
Cornblatt, BA, Carrión, RE, Addington, J, Seidman, L, Walker, EF, Cannon, TD, Cadenhead, KS, Mcglashan, TH, Perkins, DO, Tsuang, MT, Woods, SW, Heinssen, R and Lencz, T (2012) Risk factors for psychosis: impaired social and role functioning. Schizophrenia Bulletin 38, 12471257.
Dias, EC, Butler, PD, Hoptman, MJ and Javitt, DC (2011) Early sensory contributions to contextual encoding deficits in schizophrenia. Archives of General Psychiatry 68, 654664.
Frith, C and Dolan, R (1996) The role of the prefrontal cortex in higher cognitive functions. Cognitive Brain Research 5, 175181.10.1016/S0926-6410(96)00054-7
Fusar-Poli, P, Bonoldi, I, Yung, AR, Borgwardt, S, Kempton, MJ, Valmaggia, L, Barale, F, Caverzasi, E and McGuire, P (2012 a) Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Archives of General Psychiatry 69, 220229.
Fusar-Poli, P, Deste, G, Smieskova, R, Barlati, S, Yung, AR, Howes, O, Stieglitz, RD, Vita, A, Mcguire, P and Borgwardt, S (2012 b) Cognitive functioning in prodromal psychosis: a meta-analysis. Archives of General Psychiatry 69, 562571.10.1001/archgenpsychiatry.2011.1592
Giuliano, AJ, Li, H, Mesholam-Gately, RI, Sorenson, SM, Woodberry, KA and Seidman, LJ (2012) Neurocognition in the psychosis risk syndrome: a quantitative and qualitative review. Current Pharmaceutical Design 18, 399415.
Glenthøj, LB, Hjorthøj, C, Kristensen, TD, Davidson, CA and Nordentoft, M (2017) The effect of cognitive remediation in individuals at ultra-high risk for psychosis: a systematic review. Nature Partner Journals Schizophrenia 3, 20.
Gold, JM, Barch, DM, Carter, CS, Dakin, S, Luck, SJ, Macdonald, AW III, Ragland, JD, Ranganath, C, Kovacs, I, Silverstein, SM and Strauss, M (2012) Clinical, functional, and intertask correlations of measures developed by the cognitive neuroscience test reliability and clinical applications for schizophrenia consortium. Schizophrenia Bulletin 38, 144152.10.1093/schbul/sbr142
Green, M (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry 153, 321330.
Green, MF, Kern, RS, Braff, DL and Mintz, J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophrenia Bulletin 26, 119136.
Guo, JY, Ragland, JD and Carter, CS (2019) Memory and cognition in schizophrenia. Molecular Psychiatry 24, 633642.
Harvey, PD and Bowie, CR (2012) Cognitive remediation in severe mental illness. Innovations in Clinical Neuroscience 9, 2730.
Henderson, D, Poppe, AB, Barch, DM, Carter, CS, Gold, JM, Ragland, JD, Silverstein, SM, Strauss, ME and Macdonald, AW III (2012) Optimization of a goal maintenance task for use in clinical applications. Schizophrenia Bulletin 38, 104113.
Ising, HK, Smit, F, Veling, W, Rietdijk, J, Dragt, S, Klaassen, RMC, Savelsberg, NSP, Boonstra, N, Nieman, DH, Linszen, DH, Wunderink, L and Van Der Gaag, M (2015) Cost-effectiveness of preventing first-episode psychosis in ultra-high-risk subjects: multi-centre randomized controlled trial. Psychological Medicine 45, 14351446.
Kahn, RS and Keefe, RS (2013) Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 70, 11071112.
Keefe, RSE, Goldberg, TE, Harvey, PD, Gold, JM, Poe, MP and Coughenour, L (2004) The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophrenia Research 68, 283297.
Keefe, RSE, Fox, KH, Harvey, PD, Cucchiaro, J, Siu, C and Loebel, A (2011) Characteristics of the MATRICS consensus cognitive battery in a 29-site antipsychotic schizophrenia clinical trial. Schizophrenia Research 125, 161168.
Kowarik, A and Templ, M (2016) Imputation with the R Package VIM. 2016, 74. p. 16.
Kraemer, HC, Yesavage, JA, Taylor, JL and Kupfer, D (2000) How can we learn about developmental processes from cross-sectional studies, or can we? The American Journal of Psychiatry 157, 163171.
Lam, M, Lee, J, Rapisarda, A, See, YM, Yang, Z, Lee, S-A, AbdulRashid, NA, Kraus, M, Subramaniam, M, Chong, S-A and Keefe, RSE (2018) Longitudinal cognitive changes in young individuals at ultrahigh risk for psychosis. JAMA Psychiatry 75, 929939.
Lesh, TA, Niendam, TA, Minzenberg, MJ and Carter, CS (2011) Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology 36, 316338.
Lin, A, Nelson, B and Yung, AR (2012) ‘At-risk’ for psychosis research: where are we heading? Epidemiology and Psychiatric Sciences 21, 329334.
MacDonald, AW III, Carter, CS, Kerns, JG, Ursu, S, Barch, DM, Holmes, AJ, Stenger, VA and Cohen, JD (2005) Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. American Journal of Psychiatry 162, 475484.
Mcfarlane, WR, Levin, B, Travis, L, Lucas, FL, Lynch, S, Verdi, M, Williams, D, Adelsheim, S, Calkins, R, Carter, CS, Cornblatt, B, Taylor, SF, Auther, AM, Mcfarland, B, Melton, R, Migliorati, M, Niendam, T, Ragland, JD, Sale, T, Salvador, M and Spring, E (2015) Clinical and functional outcomes after 2 years in the early detection and intervention for the prevention of psychosis multisite effectiveness trial. Schizophrenia Bulletin 41, 3043.
Mcglashan, TH, Miller, TJ, Woods, SW, Rosen, JL, Hoffman, RE and Davidson, L (2001) SIPS, Structured Interview for Prodromal Syndromes. New Haven, CT: PRIME Research Clinic, Yale School of Medicine.
Minzenberg, MJ, Laird, AR, Thelen, S, Carter, CS and Glahn, DC (2009) Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of General Psychiatry 66, 811822.
Morrison, AP, French, P, Walford, L, Lewis, SW, Kilcommons, A, Green, J, Parker, S and Bentall, RP (2004) Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. British Journal of Psychiatry 185, 291297.
Murray, RM and Lewis, SW (1987) Is schizophrenia a neurodevelopmental disorder? British Medical Journal (Clinical Research Ed.), 295, 681–2.
Nelson, B, Yuen, H, Wood, SJ, Lin, A, Spiliotacopoulos, D, Bruxner, A, Broussard, C, Simmons, M, Foley, DL, Brewer, WJ, Francey, SM, Amminger, GP, Thompson, A, McGorry, PD and Yung, AR (2013) Long-term follow-up of a group at ultra high risk (“prodromal”) for psychosis: the pace 400 study. JAMA Psychiatry 70, 793802.
Niendam, TA, Laird, AR, Ray, KL, Dean, YM, Glahn, DC and Carter, CS (2012) Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cognitive, Affective, & Behavioral Neuroscience 12, 241268.
Niendam, TA, Lesh, TA, Yoon, J, Westphal, AJ, Hutchison, N, Ragland, JD, Solomon, M, Minzenberg, M and Carter, CS (2014) Impaired context processing as a potential marker of psychosis risk state. Psychiatry Research 221, 1320.
Owen, MJ, O'donovan, MC, Thapar, A and Craddock, N (2011) Neurodevelopmental hypothesis of schizophrenia. The British Journal of Psychiatry: The Journal of Mental Science 198, 173175.
Roebuck-Spencer, TM, Glen, T, Puente, AE, Denney, RL, Ruff, RM, Hostetter, G and Bianchini, KJ (2017) Cognitive screening tests versus comprehensive neuropsychological test batteries: a national academy of neuropsychology education paper†. Archives of Clinical Neuropsychology 32, 491498.
Rosvold, HE, Mirsky, AF, Sarason, I, Bransome, ED Jr and Beck, LH (1956) A continuous performance test of brain damage. Journal of Consulting Psychology 20, 343350.
Seidman, LJ, Shapiro, DI, Stone, WS, Woodberry, KA, Ronzio, A, Cornblatt, BA, Addington, J, Bearden, CE, Cadenhead, KS, Cannon, TD, Mathalon, DH, Mcglashan, TH, Perkins, DO, Tsuang, MT, Walker, EF and Woods, SW (2016) Association of neurocognition with transition to psychosis: baseline functioning in the second phase of the North American prodrome longitudinal studyassociation of neurocognition dysfunction with transition to PsychosisAssociation of neurocognition dysfunction with transition to psychosis. JAMA Psychiatry 73, 12391248.10.1001/jamapsychiatry.2016.2479
Servan-Schreiber, D, Cohen, JD and Steingard, S (1996) Schizophrenic deficits in the processing of context. A test of a theoretical model. Archives Of General Psychiatry 53, 11051112.
SPSS (2017) IBM SPSS Statistics for Windows. Version 25.0. ed. Armonk, NY: IBM Corp.
Strauss, ME, Mclouth, CJ, Barch, DM, Carter, CS, Gold, JM, Luck, SJ, Macdonald, AW III, Ragland, JD, Ranganath, C, Keane, BP and Silverstein, SM (2014) Temporal stability and moderating effects of age and sex on CNTRaCS task performance. Schizophrenia Bulletin, 40, 835844.
Velthorst, E, Zinberg, J, Addington, J, Cadenhead, KS, Cannon, TD, Carrión, RE, Auther, A, Cornblatt, BA, Mcglashan, TH, Mathalon, DH, Perkins, DO, Seidman, LJ, Tsuang, MT, Walker, EF, Woods, SW, Reichenberg, A and Bearden, CE (2018) Potentially important periods of change in the development of social and role functioning in youth at clinical high risk for psychosis. Development and Psychopathology 30, 3947.
Weinberger, DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Archives Of General Psychiatry 44, 660669.
Zhang, T, Li, H, Tang, Y, Niznikiewicz, MA, Shenton, ME, Keshavan, MS, Stone, WS, Mccarley, RW, Seidman, LJ and Wang, J (2018) Validating the predictive accuracy of the NAPLS-2 psychosis risk calculator in a clinical high-risk sample from the SHARP (Shanghai At Risk for Psychosis) program. American Journal of Psychiatry 175, 906908.


Type Description Title
Supplementary materials

Guo et al. supplementary material
Guo et al. supplementary material

 Word (899 KB)
899 KB

Predicting psychosis risk using a specific measure of cognitive control: a 12-month longitudinal study

  • Joyce Y. Guo (a1) (a2), Tara A. Niendam (a1), Andrea M. Auther (a3), Ricardo E. Carrión (a3), Barbara A. Cornblatt (a3), J. Daniel Ragland (a1), Steven Adelsheim (a4), Roderick Calkins (a5), Tamara G. Sale (a6), Stephan F. Taylor (a7), William R. McFarlane (a6) (a8) and Cameron S. Carter (a1) (a2)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.