Negative Symptom Trajectories in Individuals at Clinical High Risk for Psychosis: Differences Based on Deficit Syndrome, Persistence, and Transition Status

Tanya Tran; Michael J Spilka; Ian M Raugh; Gregory P Strauss; Carrie E Bearden; Kristin S Cadenhead; Tyrone D Cannon; Barbara A Cornblatt; Matcheri Keshavan; Daniel H Mathalon; Thomas H McGlashan; Diana O Perkins; Larry J Seidman; William S Stone; Ming T Tsuang; Elaine F Walker; Scott W Woods; Jean M Addington

doi:10.1093/schizbullopen/sgad014

Negative Symptom Trajectories in Individuals at Clinical High Risk for Psychosis: Differences Based on Deficit Syndrome, Persistence, and Transition Status

Schizophr Bull Open. 2023 Jun 1;4(1):sgad014. doi: 10.1093/schizbullopen/sgad014. eCollection 2023 Jan.

Authors

Tanya Tran¹, Michael J Spilka², Ian M Raugh², Gregory P Strauss², Carrie E Bearden³, Kristin S Cadenhead⁴, Tyrone D Cannon^{5

6}, Barbara A Cornblatt⁷, Matcheri Keshavan⁸, Daniel H Mathalon⁹, Thomas H McGlashan⁶, Diana O Perkins¹⁰, Larry J Seidman⁸, William S Stone⁸, Ming T Tsuang^{4

11}, Elaine F Walker^{12

13}, Scott W Woods⁶, Jean M Addington¹⁴

Affiliations

¹ Department of Psychology, Queen's University, Kingston, ON, Canada.
² Department of Psychology, University of Georgia, Athens, GA, USA.
³ Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA.
⁴ Department of Psychiatry, UCSD, San Diego, CA, USA.
⁵ Department of Psychology, Yale University, New Haven, CT, USA.
⁶ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁷ Department of Psychiatry, Zucker Hillside Hospital, Long Island, NY, USA.
⁸ Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Boston, MA, USA.
⁹ Department of Psychiatry, UCSF, and SFVA Medical Center, San Francisco, CA, USA.
¹⁰ Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
¹¹ Institute of Genomic Medicine, University of California, La Jolla, CA, USA.
¹² Department of Psychology, Emory University, Atlanta, GA, USA.
¹³ Department of Psychiatry, Emory University, Atlanta, GA, USA.
¹⁴ Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

Abstract

Background and hypothesis: Negative symptom trajectory in clinical high risk (CHR) for psychosis is ill defined. This study aimed to better characterize longitudinal patterns of change in negative symptoms, moderators of change, and differences in trajectories according to clinical subgroups. We hypothesized that negative symptom course will be nonlinear in CHR. Clinical subgroups known to be more severe variants of psychotic illness-deficit syndrome (DS), persistent negative syndrome (PNS), and acute psychosis onset-were expected to show more severe baseline symptoms, slower rates of change, and less stable rates of symptom resolution.

Study design: Linear, curvilinear, and stepwise growth curve models, with and without moderators, were fitted to negative symptom ratings from the NAPLS-3 CHR dataset (N = 699) and within clinical subgroups.

Study results: Negative symptoms followed a downward curvilinear trend, with marked improvement 0-6 months that subsequently stabilized (6-24 months), particularly among those with lower IQ and functioning. Clinical subgroups had higher baseline ratings, but distinct symptom courses; DS vs non-DS: more rapid initial improvement, similar stability of improvements; PNS vs non-PNS: similar rates of initial improvement and stability; transition vs no transition: slower rate of initial improvement, with greater stability of this rate.

Conclusions: Continuous, frequent monitoring of negative symptoms in CHR is justified by 2 important study implications: (1) The initial 6 months of CHR program enrollment may be a key window for improving negative symptoms as less improvement is likely afterwards, (2) Early identification of clinical subgroups may inform distinct negative symptom trajectories and treatment needs.

Keywords: cognition; functioning; growth curve analysis; symptom course.

Grants and funding

U01 MH081857/MH/NIMH NIH HHS/United States