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Multimodal brain deficits shared in early-onset and adult-onset schizophrenia predict positive symptoms regardless of illness stage.

ABSTRACT: Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early-onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early-onset (EOS) and adult-onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co-varying patterns by jointly analyzing three MRI features: fractional amplitude of low-frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug-naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub-cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug-naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug-naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.

SUBMITTER: Feng A

PROVIDER: S-EPMC9248316 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe cognitive deficits of schizophrenia are largely resistant to current treatments and thus are a lifelong illness burden. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined.MethodsThe interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps-fractional amplitude of low-frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy from diffusion MRI-were investigated by using multiset canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy control subjects.ResultsOne multimodal component (canonical variant 8) was identified as both group differentiating and significantly correlated with the MCCB composite. It demonstrated 1) increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring fractional anisotropy changes in superior longitudinal fascicules, anterior thalamic radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia.ConclusionsOur results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive impairments in schizophrenia.

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Multimodal brain deficits shared in early-onset and adult-onset schizophrenia predict positive symptoms regardless of illness stage.

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