Clinical Review Article|Articles in Press

An NIMH Workshop on Non-Affective Psychosis in Midlife and Beyond: Research Agenda on Phenomenology, Clinical Trajectories, Underlying Mechanisms, and Intervention Targets

  • Ellen E. Lee
    Send correspondence and reprint requests to Ellen E. Lee, M.D., Department of Psychiatry, University of California San Diego, 9500 Gilman Drive #0664, La Jolla, CA 92023-0664.
    Department of Psychiatry (EEL, DA), University of California San Diego, La Jolla, CA

    Sam and Rose Stein Institute for Research on Aging (EEL, DA), University of California San Diego, La Jolla, CA

    Desert-Pacific Mental Illness Research Education and Clinical Center, Veterans Affairs San Diego Healthcare System (EEL), San Diego, CA
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  • David H. Adamowicz
    Department of Psychiatry (EEL, DA), University of California San Diego, La Jolla, CA

    Sam and Rose Stein Institute for Research on Aging (EEL, DA), University of California San Diego, La Jolla, CA
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  • Sophia Frangou
    Department of Psychiatry (SF), University of British Columbia, Vancouver, British Columbia, Canada

    Icahn School of Medicine at Mount Sinai (SF), New York, NY
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  • Members of the NIMH Workshop on Non-Affective Psychosis in Midlife and Beyond
    Author Footnotes
    a Members: Chairs: Sophia Frangou, MD, PhD, FRCPsych, FRCPC; Ellen E. Lee, MD;Presenters: Anissa Abi-Dargham, MD; Anthony O. Ahmed, Ph.D; Bengi Baran, PhD; Sagnik Bhattacharyya, MBBS, MD, PhD; David Castle, MD, MBChB; Carl Cohen, MD; Lisa Eyler, PhD; Jill Glausier, PhD; Phillip Harvey, PhD; Hilleke Hulshoff Pol, PhD; Elena Ivleva, MD, PhD; Dimitrios Kapogiannis, MD; Roman Kotov, PhD;Ellen E. Lee, MD; Dost Ongur, MD, PhD; Tarek Rajji, MD; Iris Sommer, MD, PhD;Theo Van Erp, PhD; Eva Velthorst, PhD; Lawrence Yang, PhDModerators: Michael Green, PhD; Dilip Jeste, MD; Lena Palaniyappan, MBBS, PhD; Judith Ford, PhD; Carol Tamminga, MD
  • Author Footnotes
    a Members: Chairs: Sophia Frangou, MD, PhD, FRCPsych, FRCPC; Ellen E. Lee, MD;Presenters: Anissa Abi-Dargham, MD; Anthony O. Ahmed, Ph.D; Bengi Baran, PhD; Sagnik Bhattacharyya, MBBS, MD, PhD; David Castle, MD, MBChB; Carl Cohen, MD; Lisa Eyler, PhD; Jill Glausier, PhD; Phillip Harvey, PhD; Hilleke Hulshoff Pol, PhD; Elena Ivleva, MD, PhD; Dimitrios Kapogiannis, MD; Roman Kotov, PhD;Ellen E. Lee, MD; Dost Ongur, MD, PhD; Tarek Rajji, MD; Iris Sommer, MD, PhD;Theo Van Erp, PhD; Eva Velthorst, PhD; Lawrence Yang, PhDModerators: Michael Green, PhD; Dilip Jeste, MD; Lena Palaniyappan, MBBS, PhD; Judith Ford, PhD; Carol Tamminga, MD
Published:January 31, 2023DOI:


      • What is the primary question addressed by this study?
        The growing population of older people with schizophrenia has specific clinical needs related to aging and chronic psychopathology that have not been fully examined by prior research studies.
      • What is the main finding of this study?
        This review presents the state of the current research regarding middle-aged and older people with schizophrenia – ranging from phenomenology, clinical trajectories, underlying biological mechanisms, and treatments. There are critical gaps in knowledge regarding longitudinal changes due to aging versus chronic illness, key sex differences in this group, and mechanistically informed interventions.
      • What is the meaning of the finding?
        We present a consensus research roadmap with research gaps and future directions to guide the design of future studies focusing on the phenomenology, clinical needs, trajectories of symptoms and cognition with aging, and underlying biological mechanisms for this critical population.


      We present a review of the state of the research in the phenomenology, clinical trajectories, biological mechanisms, aging biomarkers, and treatments for middle-aged and older people with schizophrenia (PwS) discussed at the NIMH sponsored workshop “Non-affective Psychosis in Midlife and Beyond.” The growing population of PwS has specific clinical needs that require tailored and mechanistically derived interventions. Differentiating between the effects of aging and disease progression is a key challenge of studying older PwS. This review of the workshop highlights the recent findings in this understudied clinical population and the critical gaps in knowledge and consensus for research priorities. This review showcases the major challenges and opportunities for research to advance clinical care for this growing and understudied population.

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