Aim
Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population‐neuroscience study of the Tokyo TEEN Cohort (pn‐TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence.
Methods
Participants in the first wave of the pn‐TTC (pn‐TTC‐1) study were recruited from those of the TTC study, a large‐scale epidemiological survey in which 3171 parent–adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting‐state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn‐TTC‐2) followed similar methods as in the first wave.
Results
A total of 301 parent–adolescent pairs participated in the pn‐TTC‐1 study. Moreover, 281 adolescents participated in the pn‐TTC‐2 study, 238 of whom were recruited from the pn‐TTC‐1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html.
Conclusion
The pn‐TTC project is a large‐scale and population‐neuroscience‐based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience.
The fNIRS for supplementary clinical examination could be validly applied to differentiating people with the psychosis spectrum in various clinical stages. The fNIRS is a candidate biological marker for aiding diagnosis of psychosis spectrum in routine clinical settings.
Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3′ untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.
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