Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan 1;74(1):37-46.
doi: 10.1001/jamapsychiatry.2016.2980.

Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia

Michael L Thomas  1 , Michael F Green  2 , Gerhard Hellemann  2 , Catherine A Sugar  3 , Melissa Tarasenko  1 , Monica E Calkins  4 , Tiffany A Greenwood  5 , Raquel E Gur  4 , Ruben C Gur  4 , Laura C Lazzeroni  6 , Keith H Nuechterlein  7 , Allen D Radant  8 , Larry J Seidman  9 , Alexandra L Shiluk  5 , Larry J Siever  10 , Jeremy M Silverman  10 , Joyce Sprock  5 , William S Stone  9 , Neal R Swerdlow  5 , Debby W Tsuang  8 , Ming T Tsuang  11 , Bruce I Turetsky  4 , David L Braff  5 , Gregory A Light  1
Affiliations

Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia

Michael L Thomas et al. JAMA Psychiatry. .

Abstract

Importance: Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene.

Objectives: To characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia.

Design, setting, and participants: Cross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment.

Main outcome and measures: Mismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale.

Results: Participants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (β = 0.37, P < .001), cognition had a direct effect on negative symptoms (β = -0.16, P < .001), and both cognition (β = 0.26, P < .001) and experiential negative symptoms (β = -0.75, P < .001) had direct effects on functional outcome. The indirect effect of EAP on functional outcome was significant as well (β = 0.14, P < .001). Overall, EAP had a fully mediated effect on functional outcome, engaging general rather than modality-specific cognition, with separate pathways that involved or bypassed negative symptoms.

Conclusions and relevance: The data support a model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms. Results can be used to help guide mechanistically informed, personalized treatments and support the strategy of using EAP measures as surrogate end points in early-stage procognitive intervention studies.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest Disclosures:

Dr. Green has been a consultant to: AbbVie, ACADIA, DSP, FORUM, Lundbeck, and Takeda., he is on the Scientific Board of Luc and has received research support from Amgen and Forum. Drs. Gur and Turetsky have received unrelated research support for investigator-initiated grants from Pfizer and AstraZeneca. Dr. Gur receives royalties from the Brain Resource Center and has been a consultant for Mindprint Learning. Dr. Nuechterlein has received unrelated research support from Ortho-McNeil Janssen Scientific Affairs and has consulted to Wyeth/Pfizer. Dr. Swerdlow has been a paid consultant for Neurocine, Inc. Dr. Light reports having been a consultant to Neuroverse, Envivo, and Astellas. All other authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Path Models for the Associations Among Early Auditory Information Processing, Cognition, Negative Symptoms, and Functional Outcome Constructs EAP = Early Auditory Information Processing
Figure 2
Figure 2
Correlations among Observed Indicators of Early Auditory Information Processing, Cognition, Negative Symptoms, and Functional Outcome CVLT-II = Second Edition of the California Verbal Learning Test; SANS = Scale for the Assessment of Negative symptoms; RFS = Role Functioning Scale.
Figure 3
Figure 3
Measurement Model (M0) Associations between nodes—observed variables (squares) and latent variables (circles)—are represented by edges (lines) that can be either directed (single-headed arrow) or un-directed (double-headed arrow). Coefficients for the completely standardized solution are reported in the figure. CVLT-II = Second Edition of the California Verbal Learning Test; SANS = Scale for the Assessment of Negative symptoms; RFS = Role Functioning Scale. * indicates statistical significance at p < .05.
Figure 4
Figure 4
Final Path Model (M6) Associations between nodes—observed variables (squares) and latent variables (circles)—are represented by edges (lines) that can be either directed (single-headed arrow) or un-directed (double-headed arrow). Coefficients for the completely standardized solution are reported in the figure. CVLT-II = Second Edition of the California Verbal Learning Test; SANS = Scale for the Assessment of Negative symptoms; RFS = Role Functioning Scale. * indicates statistical significance at p < .05.
See this image and copyright information in PMC

Comment in

References

    1. Braff DL. Prepulse Inhibition of the Startle Reflex: A Window on the Brain in Schizophrenia. In: NRS, editor. Behavioral Neurobiology of Schizophrenia and Its Treatment. New York, NY: Springer; 2010. - PubMed
    1. Turetsky BI, Bilker WB, Siegel SJ, Kohler CG, Gur RE. Profile of auditory information-processing deficits in schizophrenia. Psychiat Res. 2009;165(1–2):27–37. - PMC - PubMed
    1. Bilder RM, Goldman RS, Robinson D, et al. Neuropsychology of first-episode schizophrenia: Initial characterization and clinical correlates. Am J Psychiat. 2000;157(4):549–559. - PubMed
    1. Kalkstein S, Hurford I, Gur RC. Neurocognition in schizophrenia. Current Topics in Behavioral Neurosciences. 2010;4:373–390. - PubMed
    1. Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: A quantitative review of the evidence. Neuropsychology. 1998;12(3):426–445. - PubMed

MeSH terms