Thalamic Shape Abnormalities Differentially Relate to Cognitive Performance in Early-Onset and Adult-Onset Schizophrenia

Derin Cobia; Chaz Rich; Matthew J Smith; Pedro Engel Gonzalez; Will Cronenwett; John G Csernansky; Lei Wang

doi:10.3389/fpsyt.2022.803234

Thalamic Shape Abnormalities Differentially Relate to Cognitive Performance in Early-Onset and Adult-Onset Schizophrenia

Front Psychiatry. 2022 Apr 11:13:803234. doi: 10.3389/fpsyt.2022.803234. eCollection 2022.

Authors

Derin Cobia^{1

2}, Chaz Rich³, Matthew J Smith⁴, Pedro Engel Gonzalez², Will Cronenwett², John G Csernansky², Lei Wang^{2

5}

Affiliations

¹ Department of Psychology and Neuroscience Center, Brigham Young University, Provo, UT, United States.
² Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
³ Department of Psychology, University of Notre Dame, Notre Dame, IN, United States.
⁴ School of Social Work, University of Michigan, Ann Arbor, MI, United States.
⁵ Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Abstract

Early-onset schizophrenia (EOS) shares many biological and clinical features with adult-onset schizophrenia (AOS), but may represent a unique subgroup with greater susceptibility for disease onset and worsened symptomatology and progression, which could potentially derive from exaggerated neurodevelopmental abnormalities. Neurobiological explanations of schizophrenia have emphasized the involvement of deep-brain structures, particularly alterations of the thalamus, which have been linked to core features of the disorder. The aim of this study was to compare thalamic shape abnormalities between EOS and AOS subjects and determine whether unique behavioral profiles related to these differences. It was hypothesized abnormal thalamic shape would be observed in anterior, mediodorsal and pulvinar regions in both schizophrenia groups relative to control subjects, but exacerbated in EOS. Magnetic resonance T1-weighted images were collected from adult individuals with EOS (n = 28), AOS (n = 33), and healthy control subjects (n = 60), as well as collection of clinical and cognitive measures. Large deformation high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. General linear models were used to compare groups on surface shape features, and Pearson correlations were used to examine relationships between thalamic shape and behavioral measures. Results revealed both EOS and AOS groups demonstrated significant abnormal shape of anterior, lateral and pulvinar thalamic regions relative to CON (all p < 0.007). Relative to AOS, EOS exhibited exacerbated abnormalities in posterior lateral, mediodorsal and lateral geniculate thalamic regions (p = 0.003). Thalamic abnormalities related to worse episodic memory in EOS (p = 0.03) and worse working memory (p = 0.047) and executive functioning (p = 0003) in AOS. Overall, findings suggest thalamic abnormalities are a prominent feature in both early- and late-onset schizophrenia, but exaggerated in EOS and have different brain-behavior profiles for each. The persistence of these abnormalities in adult EOS patients suggests they may represent markers of disrupted neurodevelopment that uniquely relate to the clinical and cognitive aspects of the illness.

Keywords: MRI; development; neuroimaging; psychosis; surface-mapping.