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Both neurodegenerative and neurodevelopmental abnormalities have been suggested to be part of the etiopathology of severe mental illness (SMI). Neuron-specific enolase (NSE), mainly located in the neuronal cytoplasm, may indicate the process as it is upregulated after neuronal injury while a switch from non-neuronal enolase to NSE occurs during neuronal maturation.
Methods
We included 1132 adult patients with SMI [schizophrenia (SZ) or bipolar spectrum disorders], 903 adult healthy controls (HC), 32 adolescent patients with SMI and 67 adolescent HC. Plasma NSE concentrations were measured by enzyme immunoassay. For 842 adults and 85 adolescents, we used total grey matter volume (TGMV) based on T1-weighted magnetic resonance images processed in FreeSurfer v6.0. We explored NSE case-control differences in adults and adolescents separately. To investigate whether putative case-control differences in NSE were TGMV-dependent we controlled for TGMV.
Results
We found significantly lower NSE concentrations in both adult (p < 0.001) and adolescent patients with SMI (p = 0.007) compared to HC. The results remained significant after controlling for TGMV. Among adults, both patients with SZ spectrum (p < 0.001) and bipolar spectrum disorders (p = 0.005) had lower NSE than HC. In both patient subgroups, lower NSE levels were associated with increased symptom severity. Among adults (p < 0.001) and adolescents (p = 0.040), females had lower NSE concentrations than males.
Conclusion
We found lower NSE concentrations in adult and adolescent patients with SMI compared to HC. The results suggest the lack of progressive neuronal injury, and may reflect abnormal neuronal maturation. This provides further support of a neurodevelopmental rather than a neurodegenerative mechanism in SMI.
The etiology of schizophrenia (SZ) is proposed to include an interplay between a genetic risk for disease development and the biological environment of pregnancy and birth, where early adversities may contribute to the poorer developmental outcome. We investigated whether a history of birth asphyxia (ASP) moderates the relationship between intracranial volume (ICV) and intelligence in SZ, bipolar disorder (BD) and healthy controls (HC).
Methods
Two hundred seventy-nine adult patients (18–42 years) on the SZ and BD spectrums and 216 HC were evaluated for ASP based on information from the Medical Birth Registry of Norway. Participants underwent structural magnetic resonance imaging (MRI) to estimate ICV and intelligence quotient (IQ) assessment using the Wechsler Abbreviated Scale of Intelligence (WASI). Multiple linear regressions were used for analyses.
Results
We found a significant three-way interaction (ICV × ASP × diagnosis) on the outcome variable, IQ, indicating that the correlation between ICV and IQ was stronger in patients with SZ who experienced ASP compared to SZ patients without ASP. This moderation by ASP was not found in BD or HC groups. In patients with SZ, the interaction between ICV and a history of the ASP was specifically related to the verbal subcomponent of IQ as measured by WASI.
Conclusions
The significant positive association between ICV and IQ in patients with SZ who had experienced ASP might indicate abnormal neurodevelopment. Our findings give support for ICV together with verbal intellectual abilities as clinically relevant markers that can be added to prediction tools to enhance evaluations of SZ risk.
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