Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

The rise and fall of an extraordinary Ca-rich transient The discovery of ATLAS19dqr/SN 2019bkc

This work presents the observations and analysis of ATLAS19dqr/SN 2019bkc, an extraordinary rapidly evolving transient event located in an isolated environment, tens of kiloparsecs from any likely host. Its light curves rise to maximum light in 5-6 d and then display a decline of Delta m(15)similar to 5 mag. With such a pronounced decay, it has one of the most rapidly evolving light curves known for a stellar explosion. The early spectra show similarities to normal and "ultra-stripped" type Ic SNe, but the early nebular phase spectra, which were reached just over two weeks after explosion, display prominent calcium lines, marking SN 2019bkc as a Ca-rich transient. The Ca emission lines at this phase show an unprecedented and unexplained blueshift of 10 000-12 000 km s(-1). Modelling of the light curve and the early spectra suggests that the transient had a low ejecta mass of 0.2-0.4 M-circle dot and a low kinetic energy of (2-4) x 10(50) erg, giving a specific kinetic energy E-k/M-ej similar to 1 [10(51) erg]/M-circle dot. The origin of this event cannot be unambiguously defined. While the abundance distribution used to model the spectra marginally favours a progenitor of white dwarf origin through the tentative identification of ArII, the specific kinetic energy, which is defined by the explosion mechanism, is found to be more similar to an ultra-stripped core-collapse events. SN 2019bkc adds to the diverse range of physical properties shown by Ca-rich events