A Computational Neuroscience Perspective on the Shared Social Cognitive Deficits of Autism and Schizophrenia

This retrospective cohort study will examine shared neural mechanisms of social cognitive deficits in adults with autism spectrum disorder and adults with schizophrenia using existing clinical, behavioral, and neuroimaging data from National Taiwan University Hospital cohort studies. The study will include adults with autism spectrum disorder, adults with schizophrenia, and healthy control participants.

Resting-state functional magnetic resonance imaging (MRI) and structural MRI data will be analyzed to estimate default mode network functional transition indices. These indices will be compared between diagnostic groups and examined in association with social cognitive and psychiatric symptom measures, including the Social Responsiveness Scale (SRS) and the Positive and Negative Syndrome Scale (PANSS) when applicable. No new participants will be recruited, and no intervention will be administered. The study will use previously collected data from 80 adults with autism spectrum disorder, 79 adults with schizophrenia, and 108 healthy controls.

Study Overview

• Status: Active, not recruiting
• Conditions: Schizophrenia; Autism Spectrum Disorder

• Study Type: Observational
• Enrollment (Actual): 267

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This retrospective cohort study will use pre-existing clinical, behavioral, and neuroimaging data from adult participants who were previously enrolled in cohort studies conducted at National Taiwan University Hospital. The study population includes adults with autism spectrum disorder, adults with schizophrenia, and healthy control participants. Available data include structural MRI, resting-state functional MRI, and symptom or behavioral assessments relevant to social cognition and psychiatric symptoms, including the Social Responsiveness Scale and the Positive and Negative Syndrome Scale when applicable. No new participants will be prospectively recruited, and no intervention will be administered.

Description

Inclusion Criteria:

• Previously enrolled in one of the source cohort studies approved by the institutional review board of National Taiwan University Hospital.

• Adult participants belonging to one of the following groups:

  1. Autism spectrum disorder group: participants with a clinical diagnosis of autism spectrum disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
  2. Schizophrenia group: participants with a clinical diagnosis of schizophrenia according to DSM-5 criteria.
  3. Healthy control group: participants without a history of autism spectrum disorder, schizophrenia, or other major psychiatric or neurodevelopmental disorders according to available source cohort records.
• Availability of resting-state functional MRI data acquired under the study MRI protocol.
• For participants in the autism spectrum disorder group, availability of autistic trait or social functioning measures, such as the Social Responsiveness Scale, when used in symptom-association analyses.
• For participants in the schizophrenia group, availability of psychiatric symptom measures, such as the Positive and Negative Syndrome Scale, when used in symptom-association analyses.

Exclusion Criteria:

• Missing or incomplete MRI data.
• Poor-quality MRI data due to severe artifacts, failed preprocessing, failed registration, or incomplete brain coverage.
• Excessive head motion during resting-state fMRI that prevents reliable analysis.
• Missing essential demographic or diagnostic information.
• Missing required clinical or behavioral measures for specific association analyses.
• Healthy controls with documented major psychiatric or neurodevelopmental disorders, if identified in source cohort records.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Healthy controls
Schizophrenia
Autism Spectrum Disorder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Default Mode Network mean functional state transition velocity, DMNμV	DMNμV will be derived from resting-state functional MRI data. Multi-voxel activity patterns within the default mode network will be projected into a two-dimensional state space using multidimensional scaling. The Euclidean distance between consecutive functional states will be calculated, and the mean transition velocity across time points will be used as an index of default mode network functional state stability. Lower DMNμV indicates slower state transition and higher functional state stability.	Baseline / retrospective assessment from pre-existing resting-state fMRI data

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Default Mode Network Root Mean Square of Successive Differences	The root mean square of successive differences in the default mode network signal will be calculated from the mean time series of default mode network regions of interest. This measure reflects temporal variation in mean default mode network activity across consecutive resting-state fMRI time points. Lower values indicate smaller temporal variation and greater signal stability.	Baseline / retrospective assessment from existing resting-state fMRI data
Social Responsiveness Scale Score, SRS	The Social Responsiveness Scale will be used to measure autistic traits and social functioning. The SRS is a 65-item rating scale measuring the severity of social impairment and autism-related traits. Each item is rated on a 4-point scale and scored from 0 to 3, with higher scores indicating greater autistic traits or greater impairment in reciprocal social behavior. The total raw score ranges from 0 to 195. Scores will be examined in association with default mode network functional transition indices, particularly among participants with autism spectrum disorder.	Baseline / retrospective assessment from existing source cohort records
Positive and Negative Syndrome Scale Score, PANSS	The Positive and Negative Syndrome Scale will be used to assess psychiatric symptom severity in participants with schizophrenia. The PANSS consists of 30 clinician-rated items. Each item is rated on a 7-point scale from 1 to 7, where 1 indicates absent symptoms and 7 indicates extreme symptom severity. The PANSS includes three standard subscales: Positive Scale, Negative Scale, and General Psychopathology Scale. The Positive Scale contains 7 items, the Negative Scale contains 7 items, and the General Psychopathology Scale contains 16 items. The PANSS total score is calculated by summing all 30 items and ranges from 30 to 210. Higher scores indicate greater psychiatric symptom severity. Total and subscale scores may be examined in association with default mode network functional transition indices.	Baseline / retrospective assessment from existing source cohort records

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2025
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; social cognition; autism spectrum disorder; fMRI
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Schizophrenia
• Other Study ID Numbers: 202506020RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No