Previous studies have shown glutamatergic dysfunction and γ-aminobutyric acid (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with each other and lead to alterations in excitatory/inhibitory balance. The NMDAR and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN) and auditory steady-state gamma-band response (ASSR), respectively. However, no previous studies have tested the hypothesis of an abnormal association between MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of NMDAR-GABA association during the early stages of psychosis. Participants were individuals with recent-onset schizophrenia (ROSZ; N = 21), ultra-high risk (UHR; N = 27), and healthy controls (HCs; N = 24). The MMN amplitude was significantly impaired in ROSZ (p = 0.001, d = 1.20) and UHR (p = 0.003, d = 1.01) compared with HCs. The intertrial phase coherence (ITC) index of gamma-band ASSR was significantly reduced in ROSZ compared with HCs (p < 0.001, d = –1.27) and UHR (p = 0.032, d = –0.75). The event-related spectral perturbation (ERSP) index of gamma-band ASSR was significantly smaller in ROSZ compared with HCs (p < 0.001, d = −1.21). The MMN amplitude was significantly correlated with the ITC in ROSZ (r = −0.69, p < 0.001). These findings provide the first in vivo evidence that an abnormal association of the electrophysiological indices of NMDAR and GABA dysfunctions may be present in recent-onset schizophrenia.

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.

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Subcortical structures may have an important role in the pathophysiology of psychosis. Our recent mega-analysis of structural magnetic resonance imaging (MRI) data has reported subcortical volumetric and lateralization alterations in chronic schizophrenia, including leftward asymmetric increases in pallidal volume. The question remains, however, whether these characteristics may represent vulnerability to the development of psychosis or whether they are epiphenomena caused by exposure to medication or illness chronicity. Subclinical psychotic experiences (SPEs) occur in some adolescents in the general population and increase the odds of developing psychosis in young adulthood. Investigations into the association between SPEs and MRI-measured volumes of subcortical structures in the general adolescent population would clarify the issue. Here, we collected structural MRI data in a subsample (10.5–13.3 years old) of a large-scale population-based cohort and explored subcortical volume and lateralization alterations related to SPEs (N = 203). Adolescents with SPEs demonstrated significant volumetric increases in the left hippocampus, right caudate, and right lateral ventricle, as well as a marginally significant increase in the left pallidum. Furthermore, adolescents with SPEs showed significantly more leftward laterality of pallidal volume than individuals without SPEs, which replicates our mega-analysis findings in chronic schizophrenia. We suggest that leftward asymmetries in pallidal volume already present in early adolescence may underlie the premorbid predisposition for developing psychosis in later life.

Attention/Processing Speed and Executive Function at baseline may predict global functional outcome of early psychosis. These neurocognitive tests are easy to incorporate in clinical settings and, if replicated in independent samples, may be included in routine clinical assessments for prediction of functional outcome in early psychosis.