Increasing sample diversity in psychiatric genetics - Introducing a new cohort of patients with schizophrenia and controls from Vietnam - Results from a pilot study.

OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

Hypo-activity of the dorsolateral prefrontal cortex relates to increased reaction time variability in patients with schizophrenia.

Increased reaction time intra-subject variability (RT-ISV) in fast decision tasks has been confirmed in patients with schizophrenia and has been hypothesized to result from a deficit in the control of attention. Here, an attentional task and functional brain imaging were used to probe the neural correlates of increased RT-ISV in schizophrenia. Thirty patients and 30 age and sex matched controls performed the Eriksen flanker spatial attention task with concurrent measurement of brain activity using functional magnetic resonance imaging (fMRI). The behavioral measures included accuracy, mean, standard deviation of RT (RTSD), coefficient of variation of RT (RTCV) and ex-Gaussian model of RT distribution parameters (mu, sigma and tau). Larger mean RT and Ex-Gaussian mu was observed for patients compared to controls. The group difference was larger for incongruent (attentionally demanding) versus congruent trials confirming a deficit in the control of spatial attention for patients. Significant increase in RT-ISV measures (RTSD, sigma and tau) for patients compared to controls was observed and was not modulated by trial congruency. Attention modulation (congruency effect) resulted in activation of bilateral frontal and parietal areas that was not different between patients and controls. Right middle frontal, right superior temporal and bilateral cingulate areas were more active in controls compared to patients independent of congruency. Activation in ROIs extracted from attention (congruency) and group related areas correlated with RT-ISV measures (especially RTCV and tau). Hypo-activation of the right middle frontal area correlated with increased tau specifically in patients. Hypo-activity of the right prefrontal cortex predicted increased RT-ISV in schizophrenia. This effect was unrelated to the effects of spatial attention and might be linked to a deficit in the inhibitory control of action for these patients.

Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource.

Sleep spindles are characteristic electroencephalogram (EEG) signatures of stage 2 non-rapid eye movement sleep. Implicated in sleep regulation and cognitive functioning, spindles may represent heritable biomarkers of neuropsychiatric disease. Here we characterize spindles in 11,630 individuals aged 4 to 97 years, as a prelude to future genetic studies. Spindle properties are highly reliable but exhibit distinct developmental trajectories. Across the night, we observe complex patterns of age- and frequency-dependent dynamics, including signatures of circadian modulation. We identify previously unappreciated correlates of spindle activity, including confounding by body mass index mediated by cardiac interference in the EEG. After taking account of these confounds, genetic factors significantly contribute to spindle and spectral sleep traits. Finally, we consider topographical differences and critical measurement issues. Taken together, our findings will lead to an increased understanding of the genetic architecture of sleep spindles and their relation to behavioural and health outcomes, including neuropsychiatric disorders.