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Original Investigation
December 11, 2019

Long-term Changes in Cognitive Functioning in Individuals With Psychotic Disorders: Findings From the Suffolk County Mental Health Project

Author Affiliations
  • 1Department of Psychology, City, University of London, London, United Kingdom
  • 2Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, King’s College London, London, United Kingdom
  • 3Department of Clinical and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 4Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
  • 5Seaver Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York
  • 6Department of Psychology, University of North Texas, Denton
  • 7Department of Psychiatry, Stony Brook University, Stony Brook, New York
JAMA Psychiatry. 2020;77(4):387-396. doi:10.1001/jamapsychiatry.2019.3993
Key Points

Question  What is the long-term progression of cognitive functioning in individuals after first hospitalization with a psychotic disorder?

Findings  In this study of 445 people with psychotic disorders, cognitive performance declined in most domains and some of these changes were larger than expected owing to normal aging. Declines were consistent across psychotic disorders and were associated with worsening functioning and negative symptoms; also, people with psychotic disorders performed worse on all cognitive tests than control individuals (n = 260), especially after age 50 years.

Meaning  Cognitive aging may be more rapid in individuals with psychotic disorders than in the general population for some cognitive domains.


Importance  It remains uncertain whether people with psychotic disorders experience progressive cognitive decline or normal cognitive aging after first hospitalization. This information is essential for prognostication in clinical settings, deployment of cognitive remediation, and public health policy.

Objective  To examine long-term cognitive changes in individuals with psychotic disorders and to compare age-related differences in cognitive performance between people with psychotic disorders and matched control individuals (ie, individuals who had never had psychotic disorders).

Design, Setting, and Participants  The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Cognitive functioning was assessed 2 and 20 years later. Patients were recruited from the 12 inpatient facilities of Suffolk County, New York. At year 20, the control group was recruited by random digit dialing and matched to the clinical cohort on zip code and demographics. Data were collected between September 1991 and July 2015. Analysis began January 2016.

Main Outcomes and Measures  Change in cognitive functioning in 6 domains: verbal knowledge (Wechsler Adult Intelligence Scale–Revised vocabulary test), verbal declarative memory (Verbal Paired Associates test I and II), visual declarative memory (Visual Reproduction test I and II), attention and processing speed (Symbol Digit Modalities Test–written and oral; Trail Making Test [TMT]–A), abstraction-executive function (Trenerry Stroop Color Word Test; TMT-B), and verbal fluency (Controlled Oral Word Association Test).

Results  A total of 705 participants were included in the analyses (mean [SD] age at year 20, 49.4 [10.1] years): 445 individuals (63.1%) had psychotic disorders (211 with schizophrenia spectrum [138 (65%) male]; 164 with affective psychoses [76 (46%) male]; 70 with other psychoses [43 (61%) male]); and 260 individuals (36.9%) in the control group (50.5 [9.0] years; 134 [51.5%] male). Cognition in individuals with a psychotic disorder declined on all but 2 tests (average decline: d = 0.31; range, 0.17-0.54; all P < .001). Cognitive declines were associated with worsening vocational functioning (Visual Reproduction test II: r = 0.20; Symbol Digit Modalities Test–written: r = 0.25; Stroop: r = 0.24; P < .009) and worsening negative symptoms (avolition: Symbol Digit Modalities Test–written: r = −0.24; TMT-A: r = −0.21; Stroop: r = −0.21; all P < .009; inexpressivity: Stroop: r = −0.22; P < .009). Compared with control individuals, people with psychotic disrders showed age-dependent deficits in verbal knowledge, fluency, and abstraction-executive function (vocabulary: β = −0.32; Controlled Oral Word Association Test: β = −0.32; TMT-B: β = 0.23; all P < .05), with the largest gap among participants 50 years or older.

Conclusions and Relevance  In individuals with psychotic disorders, most cognitive functions declined over 2 decades after first hospitalization. Observed declines were clinically significant. Some declines were larger than expected due to normal aging, suggesting that cognitive aging in some domains may be accelerated in this population. If confirmed, these findings would highlight cognition as an important target for research and treatment during later phases of psychotic illness.

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    3 Comments for this article
    Both Mesolimbic overactivity and Neuroleptic Antagonism are detrimental to the Prefrontal Neocortex
    Brian Trappler, M.D. F.A.C.P. | Sephardic Nursing and Rehabilitation Center
    Two factors contributing to degeneration of Neocortical cells in the P.F.C. are the overload by Mesocortical hyperactivity, and the Chronic use of D-1 and D-2 Receptors by long-term exposure to Neuroleptic drugs.
    Drug Analysis Consideration
    Andres Marcelo Trevino-Alvarez, MD, Psychiatry Resident | Psychiatry Department, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Universidad Autonoma de Nuevo Leon
    The report by Fett et al provides valuable results, however we suggest for caution in its interpretation(1). The comparison of patients with psychotic disorders versus matched controls is appropriate in methodological terms, however there is no consideration for drug exposure as reported by the authors(1). The broad employment of antipsychotics in psychiatric disorders with and without psychotic symptoms(2) and their adverse effects relevant to the study outcomes, such as cognitive and sedative effects(3) suggest an important variable that should be considered for the main outcome. Global cognition response varies among different antipsychotics as well in schizophrenia patients(4). The suggestion of considering this limitation can help us better understand and employ the evidence provided.

    1. Fett, A. J., Velthorst, E., Reichenberg, A., Ruggero, C. J., Callahan, J. L., Fochtmann, L. J., … Kotov, R. (2019). Long-term Changes in Cognitive Functioning in Individuals With Psychotic Disorders: Findings From the Suffolk County Mental Health Project. JAMA Psychiatry, 8101. https://doi.org/10.1001/jamapsychiatry.2019.3993
    2. Maher, A. R., Maglione, M., Bagley, S., Suttorp, M., Hu, J.-H., Ewing, B., … Shekelle, P. G. (2011). Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis. JAMA, 306(12), 1359–1369. https://doi.org/10.1001/jama.2011.1360
    3. Longden, E., & Read, J. (2016). Assessing and reporting the adverse effects of antipsychotic medication: A systematic review of clinical studies, and prospective, retrospective, and cross-sectional research. Clinical Neuropharmacology, 39(1), 29–39. https://doi.org/10.1097/WNF.0000000000000117
    4. Zhang, J. P., Gallego, J. A., Robinson, D. G., Malhotra, A. K., Kane, J. M., & Correll, C. U. (2013). Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: A systematic review and meta-analysis. International Journal of Neuropsychopharmacology, 16(6), 1205–1218. https://doi.org/10.1017/S1461145712001277
    Cognition as an Important Target for Treatment of Schizophrenia?
    Long-Biao Cui, PhD, MD | The Second Medical Center, Chinese PLA General Hospital; Department of Clinical Psychology, Fourth Military Medical University
    To the Editor We have enormous respect for Fett and colleagues who most recently published a high quality and well considered longitudinal study in the Journal. The authors reported the 2-year and 20-year changes in cognitive functioning of first-admission patients with psychotic disorders,1 among which 211 individuals were schizophrenia spectrum. Schizophrenia has been considered as a cognitive illness,2 in which cognitive decline is the core symptom that is specific to schizophrenia.3 “Some declines were larger than expected due to normal aging,” they stated. “If confirmed, these findings would highlight cognition as an important target for research and treatment during later phases of psychotic illness.” We are writing to draw attention to the statement regarding cognition as a target for treatment of schizophrenia and other psychotic disorders.
    In schizophrenia, cognitive decline is a phenomenon in relation to the disorder. This study implies that cognitive impairment might reflect a potential mechanism underlying other symptoms, or at least a group of significant symptoms in schizophrenia. For a target for treatment, what we are struggling to explore could be the pathophysiology behind continuous cognitive decline, which may play a critical role in the etiology of schizophrenia. Following this, we are looking for biologically-based “markers” for new prevention and treatment strategies of this debilitating disease. Our November 2019 study in Schizophrenia Bulletin provided the evidence for disrupted structural connectome of first-episode medication-naïve patients with schizophrenia,4 suggesting an impaired connectome of the brain throughout the course of schizophrenia. Specifically, the neurobiological underpinning of disrupted cognitive trajectory could serve as an important target for treatment of schizophrenia.
    Moreover, there is a lack of effective therapeutic interventions targeting cognition. Transcranial direct current stimulation is a relatively novel neuro-stimulation method, holding potential effects of improving cognitive function in schizophrenia. Since cognitive deficits are strongly predictive of functional outcomes, attempts to deal with how psychosocial approaches, pharmacological treatment, and neuro-modulatory technique are effectively used for intervening cognition are valuable.
    Finally, we will comment on the investigation itself. Taken the effects of repeated testing and age into consideration, a notable limitation is neglecting to include a matched comparison group, to whom neurocognitive assessment was performed at both baseline and follow-up. However, healthy comparison subjects were only included at the 20-year point in this study, making it difficult to control confounders inherent to cross-sectional study design.

    Funding/Support: Project funded by China Postdoctoral Science Foundation (grant 2019TQ0130).

    1. Fett AJ, Velthorst E, Reichenberg A, et al. Long-term Changes in Cognitive Functioning in Individuals With Psychotic Disorders: Findings From the Suffolk County Mental Health Project. JAMA Psychiatry. 2019. doi:10.1001/jamapsychiatry.2019.3993.
    2. Kahn RS, Keefe RS. Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry. 2013;70(10):1107-1112.
    3. Zanelli J, Mollon J, Sandin S, et al. Cognitive Change in Schizophrenia and Other Psychoses in the Decade Following the First Episode. Am J Psychiatry. 2019;176(10):811-819.
    4. Cui LB, Wei Y, Xi YB, et al. Connectome-Based Patterns of First-Episode Medication-Naive Patients With Schizophrenia. Schizophr Bull. 2019;45(6):1291-1299.