Kentaro Morita

Phylogeography of White-Spotted Charr ( Salvelinus leucomaenis ) Inferred from Mitochondrial DNA Sequences

The white-spotted charr (Salvelinus leucomaenis) is a coldwater-adapted fish distributed in far-eastern Asia. To assess phylogeographic patterns of this species over most of its range in the Japanese archipelago and Sakhalin Island, Russia, we examined nucleotide sequences of the mitochondrial DNA (mtDNA) cytochrome b region (557 bp) in 141 individuals from 50 populations. A total of 33 (5.5%) nucleotide positions were polymorphic and defined 29 haplotypes. Phylogenetic analysis assigned the observed haplotypes to four main clades, which were characterized by the idiosyncrasies and discontinuity of geographic distributions. The nested clade analyses revealed that the geographical distribution patterns of some haplotypes and clades were explained by historical event such as past fragmentation. Although substantial genetic differentiation was found among the four main clades, their geographic distributions overlapped extensively in several regions. Since white-spotted charr can potentially use both freshwater and marine environments, coexistence among different lineages can be attributed to secondary contact through range expansion by migratory individuals during multiple glacial periods after interglacial isolation. Finally, our data demonstrate that the current subspecies designation does not reflect the phylogeography of this species based on mtDNA analysis. Hierarchical analysis (AMOVA) also showed that genetic variation was far more pronounced within subspecies than among subspecies (i.e., among discrete regions). These results suggest that each population, rather than each subspecies, must be treated as an evolutionarily significant unit.

Eye movement as a biomarker of schizophrenia: Using an integrated eye movement score.

Studies have shown that eye movement abnormalities are possible neurophysiological biomarkers for schizophrenia. The aim of this study was to investigate the utility of eye movement abnormalities in identifying patients with schizophrenia from healthy controls.

Electrophysiological evidence for abnormal glutamate-GABA association following psychosis onset

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.

Genome-wide Association Analysis of Eye Movement Dysfunction in Schizophrenia

Eye movements are considered endophenotypes of schizophrenia. However, the genetic factors underlying eye movement are largely unknown. In this study, we explored the susceptibility loci for four eye movement scores: the scanpath length during the free viewing test (SPL), the horizontal position gain during the fast Lissajous paradigm of the smooth pursuit test (HPG), the duration of fixations during the far distractor paradigm of the fixation stability test (DF) and the integrated eye movement score of those three scores (EMS). We found 16 SNPs relevant to the HPG that were located in 3 genomic regions (1q21.3, 7p12.1 and 20q13.12) in the patient group; however, these SNPs were intronic or intergenic SNPs. To determine whether these SNPs occur in functional non-coding regions (i.e., enhancer or promoter regions), we examined the chromatin status on the basis of publicly available epigenomic data from 127 tissues or cell lines. This analysis suggested that the SNPs on 1q21.3 and 20q13.12 are in enhancer or promoter regions. Moreover, we performed an analysis of expression quantitative trait loci (eQTL) in human brain tissues using a public database. Finally, we identified significant eQTL effects for all of the SNPs at 1q21.3 and 20q13.12 in particular brain regions.

Role of frontal white matter and corpus callosum on social function in schizophrenia

Patients with schizophrenia show severe impairment in social function and have difficulty in their daily social life. Although a recent large-scale multicenter study revealed alterations in white matter microstructures, the association between these anatomical changes and social dysfunction in schizophrenia remains unknown. Therefore, we investigated the association between the white matter integrity of regions of interest and social function in schizophrenia. A total of 149 patients with schizophrenia and 602 healthy comparison subjects (HCS) underwent DTI and completed the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-Third Edition and the Finance subscale of the University of California, San Diego, Performance-Based Skills Assessment Brief, as social indices of interest. The fractional anisotropy (FA) in the anterior corona radiata and corpus callosum was significantly lower in patients than in HCS, and the radial diffusivity (RD) in the anterior corona radiata and corpus callosum was significantly higher in patients. The Picture Arrangement and Finance scores were both significantly impaired in patients. The effect of the FA of the right anterior corona radiata on the Finance score and the Picture Arrangement score, of the RD of the right anterior corona radiata on the Picture Arrangement score, and of the RD of the corpus callosum on the Picture Arrangement score were significant. In conclusion, our results confirmed the association between structural connectivity in the right frontal white matter and corpus callosum and social function in schizophrenia. These findings may provide a foundation for developing an intervention for functional recovery in schizophrenia.

Abnormalities of eye movement are associated with work hours in schizophrenia

Eye movement abnormalities have been reported in schizophrenia; however, their influences on everyday life remain unknown. From data on 69 subjects with schizophrenia and 246 healthy subjects, we found positive correlations between eye movement measures and work hours, which were only significant in subjects with schizophrenia. This relationship was also confirmed in a multi-site dataset including 118 subjects with schizophrenia and 280 healthy subjects. These findings further strengthen our understanding of eye movement abnormalities and their relevance in clinical recovery.

Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: A longitudinal investigation

OBJECTIVES The gamma-band auditory steady-state response (ASSR) is thought to reflect the function of parvalbumin-positive γ-aminobutyric acid (GABA)-ergic interneurons and may be a candidate biomarker in early psychosis. Although previous cross-sectional studies have shown that gamma-band ASSR is reduced in early psychosis, whether reduced gamma-band ASSR could be a predictor of the long-term prognosis remains unknown. METHODS In this longitudinal study, we investigated the association between gamma-band ASSR reduction and future global symptomatic or functional outcome in early psychosis. We measured 40-Hz ASSR in 34 patients with recent-onset schizophrenia (ROSZ), 28 ultra-high risk (UHR) individuals, and 30 healthy controls (HCs) at baseline. After 1-2 years, we evaluated the global assessment of functioning (GAF) in the ROSZ (N = 20) and UHR (N = 20) groups. RESULTS The 40-Hz ASSR was significantly reduced in the ROSZ and UHR groups. The attenuated 40-Hz ASSR was correlated with the future global symptomatic outcome in the ROSZ, but not in the UHR groups. CONCLUSIONS A reduction in the gamma-band ASSR after the onset of psychosis may predict symptomatic outcomes in early psychosis. SIGNIFICANCE Gamma-band ASSR may be a potentially useful biomarker of the long-term prognosis in patients with recent-onset schizophrenia.