Hostname: page-component-7479d7b7d-t6hkb Total loading time: 0 Render date: 2024-07-15T00:34:56.015Z Has data issue: false hasContentIssue false

Neurodevelopmental vulnerability to psychosis: developmentally-based methods enable detection of early life inhibitory control deficits that predict psychotic-like experiences at the transition to adolescence

Published online by Cambridge University Press:  03 July 2023

Vanessa C. Zarubin*
Department of Psychology, Northwestern University, Evanston, IL, USA
Katherine S. F. Damme
Department of Psychology, Northwestern University, Evanston, IL, USA Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston and Chicago, IL, USA
Teresa Vargas
Department of Psychology, Northwestern University, Evanston, IL, USA
K. Juston Osborne
Department of Psychology, Northwestern University, Evanston, IL, USA
Elizabeth S. Norton
Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston and Chicago, IL, USA Department of Medical Social Sciences, Northwestern University, Chicago, IL, USA Department of Communication Sciences & Disorders, School of Communication, Northwestern University, Evanston, IL, USA
Margaret Briggs-Gowan
Department of Psychiatry, University of Connecticut Health Center, Farmington, CT, USA
Norrina B. Allen
Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston and Chicago, IL, USA Department of Preventative Medicine, Northwestern University, Chicago, IL, USA
Laurie Wakschlag
Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston and Chicago, IL, USA Department of Psychiatry, Northwestern University, Chicago, IL, USA Institute for Policy Research (IPR), Northwestern University, Chicago, IL, USA
Vijay A. Mittal
Department of Psychology, Northwestern University, Evanston, IL, USA Department of Medical Social Sciences, Northwestern University, Chicago, IL, USA Department of Psychiatry, Northwestern University, Chicago, IL, USA Institute for Policy Research (IPR), Northwestern University, Chicago, IL, USA
Corresponding author: Vanessa C. Zarubin; Email:



Inhibitory control develops in early childhood, and atypical development may be a measurable marker of risk for the later development of psychosis. Additionally, inhibitory control may be a target for intervention.


Behavioral performance on a developmentally appropriate Go/No-Go task including a frustration manipulation completed by children ages 3–5 years (early childhood; n = 107) was examined in relation to psychotic-like experiences (PLEs; ‘tween’; ages 9–12), internalizing symptoms, and externalizing symptoms self-reported at long-term follow-up (pre-adolescence; ages 8–11). ERP N200 amplitude for a subset of these children (n = 34) with electrophysiological data during the task was examined as an index of inhibitory control.


Children with lower accuracy on No-Go trials compared to Go trials in early childhood (F(1,101) = 3.976, p = 0.049), evidenced higher PLEs at the transition to adolescence 4–9 years later, reflecting a specific deficit in inhibitory control. No association was observed with internalizing or externalizing symptoms. Decreased accuracy during the frustration manipulation predicted higher internalizing, F(2,202) = 5.618, p = 0.004, and externalizing symptoms, F(2,202) = 4.663, p = 0.010. Smaller N200 amplitudes were observed on No-Go trials for those with higher PLEs, F(1,101) = 6.075, p = 0.020; no relationship was observed for internalizing or externalizing symptoms.


Long-term follow-up demonstrates for the first time a specific deficit in inhibitory control behaviorally and electrophysiology, for individuals who later report more PLEs. Decreases in task performance under frustration induction indicated risk for internalizing and externalizing symptoms. These findings suggest that pathophysiological mechanisms for psychosis are relevant and discriminable in early childhood, and further, suggest an identifiable and potentially modifiable target for early intervention.

Original Article
Copyright © The Author(s), 2023. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Abramovitch, A., Short, T., & Schweiger, A. (2021). The C factor: Cognitive dysfunction as a transdiagnostic dimension in psychopathology. Clinical Psychology Review, 86, 102007. Scholar
Ashford, J., Smit, F., van Lier, P. A. C., Cuijpers, P., & Koot, H. M. (2008). Early risk indicators of internalizing problems in late childhood: A 9-year longitudinal study. Journal of Child Psychology and Psychiatry, 49(7), 774780. ScholarPubMed
Baker, E. R., Liu, Q., & Huang, R. (2020). A view from the start: A review of inhibitory control training in early childhood. In Palermo, S. & Bartoli, M. (Eds.), Inhibitory control training – a multidisciplinary approach (pp. 113). London, England: IntechOpen. Scholar
Blair, M., Nitzburg, G. C., DeRosse, P., & Karlsgodt, K. H. (2018). Relationship between executive function attachment style and psychotic like experiences in typically developing youth. Schizophrenia Research, 197, 428433. ScholarPubMed
Bolhuis, K., Koopman-Verhoeff, M. E., Blanken, L. M. E., Cibrev, D., Jaddoe, V. W. V., Verhulst, F. C., … Tiemeier, H. (2018). Psychotic like experiences in pre adolescence what precedes the antecedent symptoms of severe mental illness. Acta Psychiatrica Scandinavica, 138(1), 1525. ScholarPubMed
Bowie, B. H. (2010). Emotion regulation related to children's future externalizing and internalizing behaviors. Journal of Child and Adolescent Psychiatric Nursing, 23(2), 7483. ScholarPubMed
Briggs-Gowan, M. J., Estabrook, R., Henry, D., Grasso, D. G., Burns, J., McCarthy, K. J., … Wakschlag, L. S. (2019). Parsing dimensions of family violence exposure in early childhood: Shared and specific contributions to emergent psychopathology and impairment. Child Abuse & Neglect, 87, 100111. ScholarPubMed
Brooker, R. J., Bates, J. E., Buss, K. A., Canen, M. J., Dennis-Tiwary, T. A., Gatzke-Kopp, L. M., … Schmidt, L. A. (2020). Conducting event-related potential (ERP) research with young children: A review of components, special considerations, and recommendations for research on cognition and emotion. Journal of Psychophysiology, 34(3), 137158. ScholarPubMed
Buss, K. A., Kiel, E. J., Morales, S., & Robinson, E. (2014). Toddler inhibitory control, bold response to novelty, and positive affect predict externalizing symptoms in kindergarten: Inhibitory control, positive affect, and externalizing. Social Development, 23(2), 232249. ScholarPubMed
Carlson, S. M. (2005). Developmentally sensitive measures of executive function in preschool children. Developmental Neuropsychology, 28(2), 595616. ScholarPubMed
Chikara, R. K., Komarov, O., & Ko, L. W. (2018). Neural signature of event-related N200 and P300 modulation in parietal lobe during human response inhibition. International Journal of Computational Biology and Drug Design, 11(1/2), 171. Scholar
Ciesielski, K. T., Harris, R. J., & Cofer, L. F. (2004). Posterior brain ERP patterns related to the go/no-go task in children. Psychophysiology, 41(6), 882892. Scholar
Costello, E. J., Copeland, W., & Angold, A. (2011). Trends in psychopathology across the adolescent years: What changes when children become adolescents, and when adolescents become adults? Journal of Child Psychology and Psychiatry, 52(10), 10151025. ScholarPubMed
Cougnard, A., Marcelis, M., Myin-Germeys, I., De Graaf, R., Vollebergh, W., Krabbendam, L., … Van Os, J. (2007). Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness–persistence model. Psychological Medicine, 37(04), 513. ScholarPubMed
Damme, K. S. F., Norton, E. S., Briggs-Gowan, M. J., Wakschlag, L. S., & Mittal, V. A. (2022). Developmental patterning of irritability enhances prediction of psychopathology in preadolescence: Improving RDoC with developmental science. Journal of Psychopathology and Clinical Science, 131(6), 556566. ScholarPubMed
Davies, C., Cipriani, A., Ioannidis, J. P. A., Radua, J., Stahl, D., Provenzani, U., … Fusar-Poli, P. (2018). Lack of evidence to favor specific preventive interventions in psychosis: A network meta-analysis. World Psychiatry, 17(2), 196209. ScholarPubMed
Deveney, C. M., Briggs-Gowan, M. J., Pagliaccio, D., Estabrook, C. R., Zobel, E., Burns, J. L., … Wakschlag, L. S. (2019). Temporally sensitive neural measures of inhibition in preschool children across a spectrum of irritability. Developmental Psychobiology, 61(2), 216227. ScholarPubMed
Doan, S. N., Fuller-Rowell, T. E., & Evans, G. W. (2012). Cumulative risk and adolescent's internalizing and externalizing problems: The mediating roles of maternal responsiveness and self-regulation. Developmental Psychology, 48(6), 15291539. ScholarPubMed
Doege, K., Kumar, M., Bates, A. T., Das, D., Boks, M. P. M., & Liddle, P. F. (2010). Time and frequency domain event-related electrical activity associated with response control in schizophrenia. Clinical Neurophysiology, 121(10), 17601771. ScholarPubMed
Dolphin, L., Dooley, B., & Fitzgerald, A. (2015). Prevalence and correlates of psychotic like experiences in a nationally representative community sample of adolescents in Ireland. Schizophrenia Research, 169(1–3), 241247. Scholar
Dumontheil, I. (2016). Adolescent brain development. Current Opinion in Behavioral Sciences, 10, 3944. Scholar
Fryer, S. L., Roach, B. J., Ford, J. M., Donaldson, K. R., Calhoun, V. D., Pearlson, G. D., … Mathalon, D. H. (2019). Should I stay or should I go? FMRI study of response inhibition in early illness schizophrenia and risk for psychosis. Schizophrenia Bulletin, 45(1), 158168. ScholarPubMed
Fusar-Poli, P., McGorry, P. D., & Kane, J. M. (2017). Improving outcomes of first-episode psychosis: An overview. World Psychiatry, 16(3), 251265. ScholarPubMed
Goschke, T. (2014). Dysfunctions of decision-making and cognitive control as transdiagnostic mechanisms of mental disorders: Advances, gaps, and needs in current research: Dysfunctions of decision-making and cognitive control. International Journal of Methods in Psychiatric Research, 23(S1), 4157. ScholarPubMed
Gotra, M. Y., Hill, S. K., Gershon, E. S., Tamminga, C. A., Ivleva, E. I., Pearlson, G. D., … Keedy, S. K. (2020). Distinguishing patterns of impairment on inhibitory control and general cognitive ability among bipolar with and without psychosis, schizophrenia, and schizoaffective disorder. Schizophrenia Research, 223, 148157. ScholarPubMed
Grabell, A. S., Olson, S. L., Tardif, T., Thompson, M. C., & Gehring, W. J. (2017). Comparing self-regulation-associated event related potentials in preschool children with and without high levels of disruptive behavior. Journal of Abnormal Child Psychology, 45(6), 11191132. ScholarPubMed
Groom, M. J., Bates, A. T., Jackson, G. M., Calton, T. G., Liddle, P. F., & Hollis, C. (2008). Event-related potentials in adolescents with schizophrenia and their siblings: A comparison with attention-deficit/hyperactivity disorder. Biological Psychiatry, 63(8), 784792. ScholarPubMed
Hentges, R. F., Weaver Krug, C. M., Shaw, D. S., Wilson, M. N., Dishion, T. J., & Lemery-Chalfant, K. (2020). The long-term indirect effect of the early family check-up intervention on adolescent internalizing and externalizing symptoms via inhibitory control. Development and Psychopathology, 32(4), 15441554. ScholarPubMed
Hoyniak, C. P., Petersen, I. T., Bates, J. E., & Molfese, D. L. (2018). The neural correlates of temperamental inhibitory control in toddlers. Philosophical Transactions of the Royal Society B: Biological Sciences, 373(1744), 20170160. ScholarPubMed
Hum, K. M., Manassis, K., & Lewis, M. D. (2013). Neural mechanisms of emotion regulation in childhood anxiety: Neural mechanisms underlying childhood anxiety. Journal of Child Psychology and Psychiatry, 54(5), 552564. ScholarPubMed
Insel, T. R. (2010). Rethinking schizophrenia. Nature, 468(7321), 187193. ScholarPubMed
Johnstone, S. J., Pleffer, C. B., Barry, R. J., Clarke, A. R., & Smith, J. L. (2005). Development of inhibitory processing during the Go/NoGo task. Journal of Psychophysiology, 19(1), 1123. Scholar
Jonkman, L. M. (2006). The development of preparation, conflict monitoring and inhibition from early childhood to young adulthood; a Go/Nogo ERP study. Brain Research, 1097(1), 181193. ScholarPubMed
Kaufman, J., Birmaher, B., Brent, D. A., Ryan, N. D., & Rao, U. (2000). K-SADS-PL. Journal of the American Academy of Child & Adolescent Psychiatry, 39(10), 1208. ScholarPubMed
Kelleher, I., & Cannon, M. (2011). Psychotic like experiences in the general population characterizing a high risk group for psychosis. Psychological Medicine, 41(1), 16. Scholar
Kelleher, I., Harley, M., Murtagh, A., & Cannon, M. (2011). Are screening instruments valid for psychotic like experiences a validation study of screening questions for psychotic like experiences using in depth clinical interview. Schizophrenia Bulletin, 37(2), 362369. ScholarPubMed
Klein, D. N., Dougherty, L. R., Kessel, E. M., Silver, J., & Carlson, G. A. (2021). A transdiagnostic perspective on youth irritability. Current Directions in Psychological Science, 30(5), 437443. ScholarPubMed
Kooijmans, R., Scheres, A., & Oosterlaan, J. (2000). Response inhibition and measures of psychopathology: A dimensional analysis. Child Neuropsychology, 6(3), 175184. ScholarPubMed
Lamm, C., & Lewis, M. D. (2010). Developmental change in the neurophysiological correlates of self-regulation in high- and low-emotion conditions. Developmental Neuropsychology, 35(2), 156176. ScholarPubMed
Lewis, M. D., Lamm, C., Segalowitz, S. J., Stieben, J., & Zelazo, P. D. (2006). Neurophysiological correlates of emotion regulation in children and adolescents. Journal of Cognitive Neuroscience, 18(3), 430443. ScholarPubMed
Lewis, M. D., & Stieben, J. (2004). Emotion regulation in the brain: Conceptual issues and directions for developmental research. Child Development, 75(2), 371376. ScholarPubMed
Liu, R., Calkins, S. D., & Bell, M. A. (2018). Fearful inhibition, inhibitory control, and maternal negative behaviors during toddlerhood predict internalizing problems at age 6. Journal of Abnormal Child Psychology, 46(8), 16651675. ScholarPubMed
MacNeill, L. A., Allen, N. B., Poleon, R. B., Vargas, T., Osborne, K. J., Damme, K. S. F., … Wakschlag, L. S. (2021). Translating RDoC to real-world impact in developmental psychopathology: A neurodevelopmental framework for application of mental health risk calculators. Development and Psychopathology, 33(5), 16651684. ScholarPubMed
McGorry, P. D., Hartmann, J. A., Spooner, R., & Nelson, B. (2018a). Beyond the ‘at risk mental state’ concept: Transitioning to transdiagnostic psychiatry. World Psychiatry, 17(2), 133142. ScholarPubMed
McGorry, P. D., Ratheesh, A., & O'Donoghue, B. (2018b). Early intervention – an implementation challenge for 21st century mental health care. JAMA Psychiatry, 75(6), 545. ScholarPubMed
McTeague, L. M., Goodkind, M. S., & Etkin, A. (2016). Transdiagnostic impairment of cognitive control in mental illness. Journal of Psychiatric Research, 83, 3746. ScholarPubMed
Mittal, V. A., Pelletier-Baldelli, A., Trotman, H., Kestler, L., Bollini, A., & Walker, E. (2016). Schizophrenia spectrum and other psychotic disorders. In Maddux, J. E. & Winstead, B. A. (Eds.), Psychopathology: Foundations for a contemporary understanding (pp. 318340). New York, NY, United States: Routledge/Taylor & Francis Group.Google Scholar
Mittal, V. A., & Wakschlag, L. S. (2017). Research domain criteria (RDoC) grows up: Strengthening neurodevelopment investigation within the RDoC framework. Journal of Affective Disorders, 216, 3035. ScholarPubMed
Moadab, I., Gilbert, T., Dishion, T. J., & Tucker, D. M. (2010). Frontolimbic activity in a frustrating task: Covariation between patterns of coping and individual differences in externalizing and internalizing symptoms. Development and Psychopathology, 22(2), 391404. Scholar
Nelson, L. D., Strickland, C., Krueger, R. F., Arbisi, P. A., & Patrick, C. J. (2016). Neurobehavioral traits as transdiagnostic predictors of clinical problems. Assessment, 23(1), 7585. ScholarPubMed
Nigg, J. T. (2017). Annual research review: On the relations among self-regulation, self-control, executive functioning, effortful control, cognitive control, impulsivity, risk-taking, and inhibition for developmental psychopathology. Journal of Child Psychology and Psychiatry, 58(4), 361383. ScholarPubMed
Osborne, K. J., Walther, S., Shankman, S. A., & Mittal, V. A. (2020). Psychomotor slowing in schizophrenia: Implications for endophenotype and biomarker development. Biomarkers in Neuropsychiatry, 2, 100016. ScholarPubMed
Owen, M. J., Craddock, N., & Jablensky, A. (2007). The genetic deconstruction of psychosis. Schizophrenia Bulletin, 33(4), 905911. ScholarPubMed
Pietto, M. L., Giovannetti, F., Segretin, M. S., Belloli, L. M. L., Lopez-Rosenfeld, M., Goldin, A. P., … Lipina, S. J. (2018). Enhancement of inhibitory control in a sample of preschoolers from poor homes after cognitive training in a kindergarten setting: Cognitive and ERP evidence. Trends in Neuroscience and Education, 13, 3442. Scholar
Quistberg, K. A., & Mueller, U. (2020). Prospective relations between kindergarteners’ executive function skills and their externalizing and internalizing behaviors. The Clinical Neuropsychologist, 34(4), 845862. ScholarPubMed
Rajkumar, R. P. (2014). Childhood attachment and schizophrenia: The ‘attachment-developmental-cognitive’ (ADC) hypothesis. Medical Hypotheses, 83(3), 276281. ScholarPubMed
Rueda-Delgado, L. M., O'Halloran, L., Enz, N., Ruddy, K. L., Kiiski, H., Bennett, M., … Whelan, R. (2021). Brain event-related potentials predict individual differences in inhibitory control. International Journal of Psychophysiology, 163, 2234. ScholarPubMed
Schachar, R., & Logan, G. D. (1990). Impulsivity and inhibitory control in normal development and childhood psychopathology. Developmental Psychology, 26(5), 710720. Scholar
Semlitsch, H. V., Anderer, P., Schuster, P., & Presslich, O. (1986). A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. Psychophysiology, 23(6), 695703. Scholar
Shanmugan, S., Wolf, D. H., Calkins, M. E., Moore, T. M., Ruparel, K., Hopson, R. D., … Satterthwaite, T. D. (2016). Common and dissociable mechanisms of executive system dysfunction across psychiatric disorders in youth. American Journal of Psychiatry, 173(5), 517526. ScholarPubMed
Stieben, J., Lewis, M. D., Granic, I., Zelazo, P. D., Segalowitz, S., & Pepler, D. (2007). Neurophysiological mechanisms of emotion regulation for subtypes of externalizing children. Development and Psychopathology, 19(02), 455480. ScholarPubMed
Sætren, S. S., Augusti, E.-M., & Hafstad, G. S. (2021). Affective inhibitory control and risk for internalizing problems in adolescents exposed to child maltreatment: A population-based study. Journal of Abnormal Psychology, 130(2), 113125. ScholarPubMed
Troller-Renfree, S., Zeanah, C. H., Nelson, C. A., & Fox, N. A. (2018). Neural and cognitive factors influencing the emergence of psychopathology: Insights from the Bucharest early intervention project. Child Development Perspectives, 12(1), 2833. ScholarPubMed
Utendale, W. T., & Hastings, P. D. (2011). Developmental changes in the relations between inhibitory control and externalizing problems during early childhood. Infant and Child Development, 20(2), 181193. Scholar
Vargas, T. G., & Mittal, V. A. (2022). Brain morphometry points to emerging patterns of psychosis, depression, and anxiety vulnerability over a 2-year period in childhood. Psychological Medicine, 53(8), 113. Scholar
Wakschlag, L. S., Estabrook, R., Petitclerc, A., Henry, D., Burns, J. L., Perlman, S. B., … Briggs-Gowan, M. L. (2015). Clinical implications of a dimensional approach: The normal: Abnormal spectrum of early irritability. Journal of the American Academy of Child & Adolescent Psychiatry, 54(8), 626634. ScholarPubMed
Wakschlag, L. S., Roberts, M. Y., Flynn, R. M., Smith, J. D., Krogh-Jespersen, S., Kaat, A. J., … Davis, M. M. (2019). Future directions for early childhood prevention of mental disorders: A road map to mental health, earlier. Journal of Clinical Child & Adolescent Psychology, 48(3), 539554. ScholarPubMed
Walker, E. F. (1990). Prediction of adult-onset schizophrenia from childhood home movies of the patients. American Journal of Psychiatry, 147(8), 10521056. ScholarPubMed
Watson, A. J., & Bell, M. A. (2013). Individual differences in inhibitory control skills at three years of age. Developmental Neuropsychology, 38(1), 121. ScholarPubMed
White, L. K., McDermott, J. M., Degnan, K. A., Henderson, H. A., & Fox, N. A. (2011). Behavioral inhibition and anxiety: The moderating roles of inhibitory control and attention shifting. Journal of Abnormal Child Psychology, 39(5), 735747. ScholarPubMed
Woltering, S., Liu, Z., Rokeach, A., & Tannock, R. (2013). Neurophysiological differences in inhibitory control between adults with ADHD and their peers. Neuropsychologia, 51(10), 18881895. ScholarPubMed
Supplementary material: File

Zarubin et al. supplementary material 1

Zarubin et al. supplementary material
Download Zarubin et al. supplementary material 1(File)
File 276.7 KB
Supplementary material: File

Zarubin et al. supplementary material 2

Zarubin et al. supplementary material
Download Zarubin et al. supplementary material 2(File)
File 24.1 KB
Supplementary material: File

Zarubin et al. supplementary material 3

Zarubin et al. supplementary material
Download Zarubin et al. supplementary material 3(File)
File 24 KB