Previous findings in psychosis have revealed mixed findings on glutamate (Glu) levels in the dorsal anterior cingulate cortex (dACC). Factors such as illness chronicity, methodology, and medication status have impeded a more nuanced evaluation of Glu in psychosis. The goal of this longitudinal neuroimaging study was to investigate the role of antipsychotics on Glu in the dACC in antipsychotic-naïve first-episode psychosis (FEP) patients.

We enrolled 117 healthy controls (HCs) and 113 antipsychotic-naïve FEP patients for this study. 3T proton magnetic resonance spectroscopy (1H-MRS; PRESS; TE = 80 ms) data from a voxel prescribed in the dACC were collected from all participants at baseline, 6, and 16 weeks following antipsychotic treatment. Glutamate levels were quantified using the QUEST algorithm and analyzed longitudinally using linear mixed-effects models.

We found that baseline dACC glutamate levels in FEP were not significantly different than those of HCs. Examining Glu levels in FEP revealed a decrease in Glu levels after 16 weeks of antipsychotic treatment; this effect was weaker in HC. Finally, baseline Glu levels were associated with decreases in positive symptomology.

We report a progressive decrease of Glu levels over a period of 16 weeks after initiation of treatment and a baseline Glu level association with a reduction in positive symptomology, suggestive of a potential mechanism of antipsychotic drug (APD) action. Overall, these findings suggest that APDs can influence Glu within a period of 16 weeks, which has been deemed as an optimal window for symptom alleviation using APDs.

Genetically informative twin studies have consistently found that individual differences in anxiety and depression symptoms are stable and primarily attributable to time-invariant genetic influences, with non-shared environmental influences accounting for transient effects.

We explored the etiology of psychological and somatic distress in 2279 Australian twins assessed up to six times between ages 12–35. We evaluated autoregressive, latent growth, dual-change, common, and independent pathway models to identify which, if any, best describes the observed longitudinal covariance and accounts for genetic and environmental influences over time.

An autoregression model best explained both psychological and somatic distress. Familial aggregation was entirely explained by additive genetic influences, which were largely stable from ages 12 to 35. However, small but significant age-dependent genetic influences were observed at ages 20–27 and 32–35 for psychological distress and at ages 16–19 and 24–27 for somatic distress. In contrast, environmental influences were predominantly transient and age-specific.

The longitudinal trajectory of psychological distress from ages 12 to 35 can thus be largely explained by forward transmission of a stable additive genetic influence, alongside smaller age-specific genetic innovations. This study addresses the limitation of previous research by exhaustively exploring alternative theoretical explanations for the observed patterns in distress symptoms over time, providing a more comprehensive understanding of the genetic and environmental factors influencing psychological and somatic distress across this age range.

Recent stressful life events (SLEs) are an established risk factor for a range of psychiatric disorders. Animal studies have shown evidence of gray matter (GM) reductions associated with stress, and previous work has found similar associations in humans. However longitudinal studies investigating the association between stress and changes in brain structure are limited.

The current study uses longitudinal data from the UK Biobank and comprises 4,543 participants with structural neuroimaging and recent SLE data (mean age = 61.5 years). We analyzed the association between recent SLEs and changes in brain structure, determined using the longitudinal FreeSurfer pipeline, focusing on total GM volume and five a priori brain regions: the hippocampus, amygdala, anterior cingulate cortex, orbitofrontal cortex, and insula. We also examined if depression and childhood adversity moderated the relationship between SLEs and brain structure.

Individuals who had experienced recent SLEs exhibited a slower rate of hippocampal decrease over time compared to individuals who did not report any SLEs. Individuals with depression exhibited smaller GM volumes when exposed to recent SLEs. There was no effect of childhood adversity on the relationship between SLEs and brain structure.

Our findings suggest recent SLEs are not directly associated with an accelerated decline in brain volumes in a population sample of older adults, but instead may alter brain structure via affective disorder psychopathology. Further work is needed to investigate the effects of stress in younger populations who may be more vulnerable to stress-induced changes, and may yet pinpoint brain regions linked to stress-related disorders.

Neuropsychiatric symptoms (NPS) are considered diagnostic and prognostic indicators of dementia and are attributable to neurodegenerative processes. Little is known about the prognostic value of early NPS on executive functioning (EF) decline in Alzheimer’s disease and related dementias (ADRD). We examined whether baseline NPS predicted the rate of executive function (EF) decline among older adults with ADRD.

Older adults (n = 1625) with cognitive impairment were selected from the National Alzheimer’s Coordinating Center database. EF was estimated with a latent factor indicated by scores on Number Span Backward, Letter Fluency, and Trail Making-Part B. A curve of factors (CUFF) latent growth curve model was estimated to examine rate of change over four years. Baseline NPS severity was entered as a predictor in the model to examine its influence on the rate of change in EF over time.

The CUFF models exhibited good fit. EF significantly declined over four waves (slope = −.16, p < .001). Initial visit NPS severity predicted decline in EF (slope = .013, p < .001), such that those with greater baseline NPS severity demonstrated a more rapid decline in EF performance over time. Presence of 2 NPS significantly predicted EF decline, and those with medium total NPS severity (NPS score of 2–4) at baseline exhibited a sharper decline in EF.

Findings underscore the importance of targeting NPS early across ADRD syndromes to minimize EF decline, offering novel insights into how early NPS treatment may alter cognitive trajectories. We provide an innovative, user-friendly web-based application that may be helpful for personalized treatment planning.

Prior studies suggest that childhood maltreatment is associated with altered hippocampal volume. However, longitudinal studies are currently scarce, making it difficult to determine how alterations in hippocampal volume evolve over time. The current study examined the relationship between childhood maltreatment and hippocampal volumetric development across childhood and adolescence in a community sample.

In this longitudinal study, a community sample of 795 participants underwent brain magnetic resonance imaging (MRI) in three waves spanning ages 6–21 years. Childhood maltreatment was assessed using parent-report and children´s self-report at baseline (6–12 years old). Mixed models were used to examine the relationship between childhood maltreatment and hippocampal volume across time.

The quadratic term of age was significantly associated with both right and left hippocampal volume development. High exposure to childhood maltreatment was associated with reduced offset of right hippocampal volume and persistent reduced volume throughout adolescence.

Critically, the relationship between childhood maltreatment and reduced right hippocampal volume remained significant after adjusting for the presence of any depressive disorder during late childhood and adolescence and hippocampal volume polygenic risk scores. Time-by-CM and Sex-by-CM interactions were not statistically significant.

The present study showed that childhood maltreatment is associated with persistent reduction of hippocampal volume in children and adolescents, even after adjusting for the presence of major depressive disorder and genetic determinants of hippocampal structure.

Research examining (MCI) criteria in diverse and/or health-disparate populations is limited. There is a critical need to investigate the predictive validity for incident dementia of widely used MCI definitions in diverse populations.

Eligible participants were non-Hispanic White or Black Bronx community residents, free of dementia at enrollment, with at least one annual follow-up visit after baseline. Participants completed annual neurological and neuropsychological evaluations to determine cognitive status. Dementia was defined based on DSM-IV criteria using case conferences. Cox proportional hazard models assessed predictive validity for incident dementia of four specific MCI definitions (Petersen, Jak/Bondi, number of impaired tests, Global Clinical Ratings) at baseline, controlling for age, sex, education, and race/ethnicity. Time-dependent sensitivity and specificity at 2–7 years for each definition, and Youden’s index were calculated as accuracy measures.

Participants (N = 1073) ranged in age from 70 to 100 (mean = 78.4 ± 5.3) years at baseline. The sample was 62.5% female, and educational achievement averaged 13.9 ± 3.5 years. Most participants identified as White (70.0%), though Black participants were well-represented (30.0%). In general, MCI definitions differed in sensitivity and specificity for incident dementia. However, there were no significant differences in Youden’s index for any definition, across all years of follow-up.

This work provides an important step toward improving the generalizability of the MCI diagnosis to underrepresented/health-disparate populations. While our findings suggest the studied MCI classifications are comparable, researchers and clinicians may choose to consider one method over another depending on the rationale for evaluation or question of interest.

Psychotic disorders are characterised by abnormalities in the synchronisation of neuronal responses. A 40 Hz gamma band deficit during auditory steady-state response (ASSR) measured by electroencephalogram (EEG) is a robust observation in psychosis and is associated with symptoms and functional deficits. However, the majority of ASSR studies focus on specific electrode sites, while whole scalp analysis using all channels, and the association with clinical symptoms, are rare.

In this study, we use whole-scalp 40 Hz ASSR EEG measurements – power and phase-locking factor – to establish deficits in early-stage psychosis (ESP) subjects, classify ESP status using an ensemble of machine learning techniques, identify correlates with principal components obtained from clinical/demographic/functioning variables, and correlate functional outcome after a short-term follow-up.

We identified significant spatially-distributed group level differences for power and phase locking. The performance of different machine learning techniques and interpretation of the extracted feature importance indicate that phase locking has a more predictive and parsimonious pattern than power. Phase locking is also associated with principal components composed of measures of cognitive processes. Short-term functional outcome is associated with baseline 40 Hz ASSR signals from the FCz and other channels in both phase locking and power.

This whole-scalp EEG study provides additional evidence to link deficits in 40 Hz ASSRs with cognition and functioning in ESP, and corroborates with prior studies of phase locking from a subset of EEG channels. Confirming 40 Hz ASSR deficits serves as a candidate phenotype to identify circuit dysfunctions and a biomarker for clinical outcomes in psychosis.

Anorexia nervosa is a psychiatric disorder characterised by undernutrition, significantly low body weight and large, although possibly transient, reductions in brain structure. Advanced brain ageing tracks accelerated age-related changes in brain morphology that have been linked to psychopathology and adverse clinical outcomes.

The aim of the current case–control study was to characterise cross-sectional and longitudinal patterns of advanced brain age in acute anorexia nervosa and during the recovery process.

Measures of grey- and white-matter-based brain age were obtained from T1-weighted magnetic resonance imaging scans of 129 acutely underweight female anorexia nervosa patients (of which 95 were assessed both at baseline and after approximately 3 months of nutritional therapy), 39 recovered patients and 167 healthy female controls, aged 12–23 years. The difference between chronological age and grey- or white-matter-based brain age was calculated to indicate brain-predicted age difference (BrainAGEGM and BrainAGEWM).

Acute anorexia nervosa patients at baseline, but not recovered patients, showed a higher BrainAGEGM of 1.79 years (95% CI [1.45, 2.13]) compared to healthy controls. However, the difference was largely reduced for BrainAGEWM. After partial weight restoration, BrainAGEGM decreased substantially (beta = −1.69; CI [−1.93, −1.46]). BrainAGEs were unrelated to symptom severity or depression, but larger weight gain predicted larger normalisation of BrainAGEGM in the longitudinal patient sample (beta = −0.65; CI [−0.75, −0.54]).

Our findings suggest that in patients with anorexia nervosa, undernutrition is an important predictor of advanced grey-matter-based brain age, which itself might be transient in nature and largely undetectable after weight recovery.

Pain resilience and regional gray matter volume (rGMV) are established correlates of adaptation to chronic pain within cross-sectional studies. Extending such work, this prospective cohort study tested the status of baseline pain resilience dimension scores and rGMV as risk factors for subsequent exacerbations in chronic pain disability and intensity.

142 adults with chronic musculoskeletal pain completed an initial assessment comprising a structural magnetic resonance imaging scan and self-report measures of cognitive/affective positivity and behavioral perseverance pain resilience dimensions, disability, pain intensity, and demographics. Disability and pain intensity were outcomes re-assessed at a 6-month follow-up. The impact of pain resilience dimension scores and identified rGMV sites on follow-up outcomes was examined after controlling for other baseline correlates of outcomes. Mediating effects of identified rGMV sites on pain resilience dimension-follow-up outcome relations were also evaluated.

Aside from the significant multivariate effect of lower behavioral perseverance and cognitive/affective positivity scores, augmented left precuneus, temporal pole, superior temporal gyrus (STG), and precentral gyrus rGMV combined to predict higher follow-up disability levels, independent of covariates. Higher left fusiform gyrus rGMV levels predicted follow-up exacerbations in pain intensity, but pain resilience dimension scores did not. Finally, left precuneus and left temporal pole STG rGMV partially mediated cognitive/affective positivity-follow-up disability relations.

Findings underscore deficits in pain resilience and increased rGMV as potential risk factors for poorer subsequent outcomes of chronic musculoskeletal pain and provide foundations for further prospective extensions as well as targeted intervention research.

Adverse childhood events (ACEs) have been linked to widespread chronic pain (CP) in various cross-sectional studies, mainly in clinical populations. However, the independent role of different ACEs on the development of different types of CP remains elusive. Accordingly, we aimed to prospectively assess the associations between specific types of ACEs with the development of multisite CP in a large population-based cohort.

Data stemmed from the three first follow-up evaluations of CoLaus|PsyCoLaus, a prospective population-based cohort study of initially 6734 participants (age range: 35–75 years). The present sample included 1537 participants with 2161 analyzable intervals (49.7% men, mean age 57.3 years). Diagnostic criteria for ACEs were elicited using semi-structured interviews and CP was assessed by self-rating questionnaires. Multinomial logistic regressions with generalized estimating equations method analyzed the relationship between the different ACEs measured in the beginning of the interval and the risk of developing multisite CP during the follow-up. Sensitivity analyses were performed to assess the predictive value of ACEs on multisite CP with neuropathic features.

Participants with a history of parental divorce or separation had an increased risk of developing multisite CP at during follow-up in comparison to those without (RR1.98; 95% CI 1.13–3.47). A strong association was highlighted between parental divorce or separation and the risk of subsequent CP with neuropathic characteristics (RR 4.21, 95% CI 1.45–12.18).

These results highlight the importance of psychotherapeutic management of people experiencing parental separation to prevent CP in the future.