Hair glucocorticoids are associated with childhood adversity, depressive symptoms and reduced global and lobar grey matter in Generation Scotland

Hypothalamic–pituitary–adrenal (HPA) axis dysregulation has been commonly reported in major depressive disorder (MDD), but with considerable heterogeneity of results; potentially due to the predominant use of acute measures of an inherently variable/phasic system. Chronic longer-term measures of HPA-axis activity have yet to be systematically examined in MDD, particularly in relation to brain phenotypes, and in the context of early-life/contemporaneous stress. Here, we utilise a temporally stable measure of cumulative HPA-axis function (hair glucocorticoids) to investigate associations between cortisol, cortisone and total glucocorticoids with concurrent measures of (i) lifetime-MDD case/control status and current symptom severity, (ii) early/current-life stress and (iii) structural neuroimaging phenotypes, in N = 993 individuals from Generation Scotland (mean age = 59.1 yrs). Increased levels of hair cortisol were significantly associated with reduced global and lobar brain volumes with reductions in the frontal, temporal and cingulate regions (βrange = −0.057 to −0.104, all PFDR < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; βrange = 0.071 to 0.115, all PFDR = < 0.05), with early-life adversity (β = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: β = −0.059, P = 0.043; nucleus accumbens: β = −0.075, PFDR = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD.

The Cone of Direct Gaze: A Stable Trait

Direct eye gaze is a potent stimulus in social interactions and is often associated with interest and approach orientation. Yet, there is remarkable variability in the range of gaze lines that people accept as being direct. A measure that is frequently used to quantify the range of gaze angles within which an observer assumes mutual gaze is the cone of direct gaze (CoDG). While individual differences in CoDG have often been examined, studies that systematically investigate the stability of an observers' CoDG over time are scarce. In two experiments, we measured the CoDG using an established paradigm and repeated the measurement after 5 min and/or after 1 week. We found high inter-individual variation, but high agreement within participants (ICCs between 0.649 and 0.855). We conclude that the CoDG can be seen as a rather stable measure, much like a personality trait.

Reliability of P3 Event-Related Potential during Working Memory Across the Spectrum of Cognitive Aging

Event-related potentials (ERPs) offer unparalleled temporal resolution in tracing distinct electrophysiological processes related to normal and pathological cognitive aging. The stability of ERPs in older individuals, who inherently show more intraindividual variability in cognitive functions, has not been established. In this test-retest reliability study, 39 older individuals (age 74.10 (5.4) years; 23 (59%) women; 15 non β-amyloid elevated, 16 β-amyloid elevated, 8 cognitively impaired) with scores on the Montreal Cognitive Assessment (MOCA) ranging between 3 and 30 completed a working memory (n-back) test with three levels of difficulty at baseline and two-week follow-up. Stability of the ERP was evaluated on grand averaged task effects for both visits. P3 peak amplitude and latency were measured in frontal channels. P3 peak amplitude at Fz, our main outcome variable, showed excellent reliability in 0-back (intraclass correlation coefficient (ICC), 95% confidence interval = 0.82 (0.67 – 0.90) and 1-back (ICC = 0.87 (0.76 – 0.93), however, only fair reliability in 2-back (ICC = 0.53 (0.09 – 0.75). Reliability of P3 peak latencies was substantially lower, with ICCs ranging between 0.17 for 2-back and 0.54 for 0-back. Generalized linear mixed models showed no confounding effect of age, group, or task difficulty on stability of P3 amplitude and latency of Fz. By contrast, MOCA scores tended to negatively correlate with P3 amplitude of Fz (p=0.07). We conclude that P3 peak amplitude and latency provide a stable measure of electrophysiological processes in older individuals. However, impaired cognition may affect the stability of the ERP response.

Erythrocyte Ascorbate Is a Potential Indicator of Steady-State Plasma Ascorbate Concentrations in Healthy Non-Fasting Individuals

Plasma vitamin C concentrations fluctuate in response to recent dietary intake; therefore levels are typically determined in the fasting state. Erythrocyte ascorbate concentrations have been shown to be similar to plasma levels, but little is known about the kinetics of ascorbate accumulation in these cells. In this study, we investigated ascorbate uptake into erythrocytes after dietary supplementation with vitamin C and compared it to changes in plasma ascorbate concentrations. Seven individuals with baseline fasting plasma vitamin C concentrations ≥ 50 µmol/L were depleted of vitamin C-containing foods and drinks for one week, and then supplemented with 250 mg vitamin C/day in addition to resuming their normal diet. Fasting or steady-state plasma ascorbate concentrations declined to almost half of their baseline concentration over the week of vitamin C depletion, and then returned to saturation within two days of beginning supplementation. Erythrocyte ascorbate concentrations exhibited a very similar profile to plasma levels, with values ~76% of plasma, and a strong linear correlation (r = 0.89, p < 0.0001). Using a pharmacokinetic study design in six individuals with baseline fasting plasma vitamin C concentrations ≥50 µmol/L, we also showed that, unlike plasma, which peaked between 2 and 4 h following ingestion of 200 mg of vitamin C, erythrocyte ascorbate concentrations did not change in the six hours after supplementation. The data from these two intervention studies indicate that erythrocyte ascorbate concentration provides a stable measure of steady-state plasma ascorbate status and could be used to monitor ascorbate status in healthy non-fasting individuals.

Test–Retest Reliability of Dual-Recorded Brainstem versus Cortical Auditory-Evoked Potentials to Speech

Auditory-evoked potentials have proven useful in the objective evaluation of sound encoding at different stages of the auditory pathway (brainstem and cortex). Yet, their utility for use in clinical assessment and empirical research relies critically on the precision and test–retest repeatability of the measure.To determine how subcortical/cortical classes of auditory neural responses directly compare in terms of their internal consistency and test–retest reliability within and between listeners.A descriptive cohort study describing the dispersion of electrophysiological measures.Eight young, normal-hearing female listeners.We recorded auditory brainstem responses (ABRs), brainstem frequency-following responses (FFRs), and cortical (P1-N1-P2) auditory-evoked potentials elicited by speech sounds in the same set of listeners. We reassessed responses within each of four different test sessions over a period of 1 mo, allowing us to detect possible changes in latency/amplitude characteristics with finer detail than in previous studies.Our findings show that brainstem and cortical amplitude/latency measures are remarkably stable; with the exception of slight prolongation of the P1 wave, we found no significant variation in any response measure. Intraclass correlation analysis revealed that the speech-evoked FFR amplitude and latency measures achieved superior repeatability (intraclass correlation coefficient >0.85) among the more widely used obligatory brainstem (ABR) and cortical (P1-N1-P2) auditory-evoked potentials. Contrasting these intersubject effects, intrasubject variability (i.e., within-subject coefficient of variation) revealed that while latencies were more stable than amplitudes, brainstem and cortical responses did not differ in their variability at the single subject level.We conclude that (1) the variability of auditory neural responses increases with ascending level along the auditory neuroaxis (cortex > brainstem) between subjects but remains highly stable within subjects and (2) speech-FFRs might provide a more stable measure of auditory function than other conventional responses (e.g., click-ABR), given their lower inter- and intrasubject variability.

Assessing Discomfort and Avoidance of Social Situations Due to Weight and Physical Appearance in Adolescents: An Exploratory Factor Analysis of a New Measure

IntroductionIn adolescence experiencing weight and physical appearance concerns is common. These body and weigh-related preoccupations are associated with anxiety and may lead adolescents to avoid social situations where their body image is exposed.AimThe present study aimed to conduct an exploratory factor analysis and explore the psychometric properties of a new measure of social situations discomfort and avoidance due to weight or physical appearance (DASSWPA) in a sample of adolescents.MethodsThe sample comprised 357 adolescents aged between 12 and 18-years-old, 195 males and 162 females, with a mean age of 14.69 (SD = 1.68). Participants completed a set of self-reported questionnaires concerning anxiety, stress and depression symptoms (DASS-21), bullying experiences (BIVES-A) and body image related shame feelings (BISS).ResultsThe DASSWPA is comprised of two separate scales: one regarding discomfort/anxiety and another one related to avoidance of social situations. Results suggested that both scales presented a similar two-factor structure. Both scales revealed good psychometric properties, including high internal consistency (α = 0.91) and an excellent temporal stability. Moreover, DASSWPA showed significant and positive associations with body image related shame feelings, victimization experiences, and anxiety, stress and depressions symptoms. Gender differences were also found, with girls presenting significantly higher levels in the anxiety/discomfort scale than boys.ConclusionThe DASSWPA proved to be a reliable and stable measure to assess anxiety and avoidance of social situations due to one's physical appearance and weight in adolescents.Disclosure of interestThe authors have not supplied their declaration of competing interest.