Neuroticism, a personality trait linked to both cardiovascular and psychiatric disorders, has been associated with cognitive decline and increased dementia risk, though the underlying neural mechanisms remain unclear. Mapping its relationship with brain structure could provide valuable insights into neural pathways and targets for early intervention.

We examined brain-wide associations between neuroticism and structural neuroimaging metrics derived from T1-, T2-weighted, and diffusion MRI in 36,901 dementia-free UK Biobank participants. Bonferroni-significant associations underwent bidirectional two-sample Mendelian randomization to evaluate the evidence for a causal relationship. Given that neuroticism is generally stable across adulthood and challenging to modify, we assessed whether these associations were mediated by health conditions (depression, anxiety, hypertension, ischemic heart disease [IHD], and diabetes) that are both consequences of neuroticism and known risk factors for dementia, and also modifiable through widely available and efficacious therapeutic interventions.

Higher neuroticism was found to be associated with reduced grey matter volumes in the frontal and limbic regions, as well as widespread differences in white matter microstructure, particularly in thalamic radiations. Genetic analyses supported a potential causal effect of neuroticism on increased diffusivity in thalamic radiations. Hypertension mediated the associations between neuroticism and both grey and white matter measures, while depression and anxiety primarily mediated associations with white matter microstructure. Contributions from IHD and diabetes were minimal.

Neuroticism is linked to widespread structural brain differences that contribute to poorer brain health, and targeting vascular and mental health may help mitigate its impact.

Structural abnormalities in cortical and subcortical brain regions are consistently observed in schizophrenia; however, substantial inter-individual variability complicates identifying clear neurobiological biomarkers. The Person-Based Similarity Index (PBSI) quantifies individual structural variability; however, its applicability across schizophrenia stages remains unclear. This study aimed to compare cortical and subcortical structural variability in recent-onset and chronic schizophrenia and explore associations with clinical measures.

Neuroimaging data from 41 patients with recent-onset schizophrenia, 32 with chronic schizophrenia, and 59 healthy controls were analyzed. The PBSI scores were calculated for cortical thickness, surface area, cortical gray matter volume, and subcortical volumes. Group differences in PBSI scores were assessed using linear regression and analysis of variance. Correlations between the PBSI scores and clinical measures were also examined.

Both patients with recent-onset and chronic schizophrenia exhibited significantly lower PBSI scores than healthy controls, indicating greater morphometric heterogeneity. However, significant differences between the recent-onset and chronic patient groups were limited to subcortical and cortical thickness PBSI scores. Correlations between PBSI scores and clinical symptoms are sparse and primarily restricted to surface area variability and symptom severity in patients with recent-onset schizophrenia.

Patients with schizophrenia show marked structural brain heterogeneity compared with healthy controls, which is detectable even in the early stages of the illness. Although there were few differences in PBSI scores between the recent-onset and chronic schizophrenia groups and limited correlations between PBSI scores and clinical measures, the PBSI may still provide valuable insights into individual differences contributing to clinical heterogeneity in schizophrenia.

A better mechanistic understanding of schizophrenia spectrum disorders is crucial to developing efficient treatment approaches. Therefore, this study investigated longitudinal interrelations between clinical outcomes, brain structure, and somatic health in post-acute individuals from the schizophrenia spectrum.

A sample of 63 post-acute patients from two independent physical exercise studies was included in the final analyses. Demographic, clinical, cognitive, and somatic data were acquired at baseline and follow-up, as were structural magnetic resonance imaging scans. Multivariate cross-lagged panel modeling including mediators was used to study the mutual interrelations over time between the clinical, neural, and somatic levels.

A higher baseline global gray matter volume and larger regional gray matter volumes of the hippocampal formation, precuneus, and posterior cingulate predicted improved clinical outcomes, such as daily-life functioning, negative symptoms, and cognition. Increases in white matter volume from baseline to follow-up resulted in significantly reduced positive symptoms and higher daily-life functioning.

Our findings suggest that stimulating neuroplasticity, especially in the hippocampal formation, precuneus, and posterior cingulate gyrus, may represent a promising treatment target in post-acute schizophrenia spectrum disorders. Physical exercise therapies and other lifestyle interventions, and brain stimulation approaches reflect potential treatment candidates. Given the exploratory character of the statistical analysis performed, these findings need to be replicated in independent longitudinal imaging cohorts of patients with schizophrenia spectrum disorders.

Cortical thickness reductions associated with chronic methamphetamine use exhibit a non-uniform spatial distribution across brain regions. A potential neurobiological mechanism underlying for this heterogeneous pattern may involve the structural and functional organization of cortical connectivity networks, which could mediate the propagation of neuroanatomical alterations. Here, we aimed to explore how brain network architecture constrains cortical thickness alterations and their clinical relevance.

The 3D-T1 images were acquired from 139 patients with methamphetamine use disorder (MUD) and 119 sex- and age-matched healthy controls. We first characterized distributed cortical thinning patterns in patients with MUD, then evaluated the relationships between regional atrophy and (1) multimodal nodal centrality measures (structural, morphological, and functional) and (2) atrophy profiles of structural connected neighbors. Individual network-weighted cortical abnormality maps were used to identify distinct MUD biotypes and related to clinical features through k-means clustering and partial least squares regression.

Cortical thinning patterns demonstrated significant associations with nodal centrality across all modalities, as well as cortical thinning of connected neighbors revealing a network-dependent atrophy architecture. Fronto-temporal regions emerged as critical epicenters, showing both high nodal centrality and strong correlations with connected neighbors’ thinning severity. We found that the individual differences in network-weighted cortical abnormality corresponded to clinical symptom variability, and distinguished two MUD biotypes associated with drug use.

Our findings suggest that cortical thinning in MUD is influenced by the brain connectome architecture, providing a mechanistic framework for understanding individual variability in addiction progression.

The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.

We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.

Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.

Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

The choroid plexus produces cerebrospinal fluid, which is crucial for glymphatic system function. Evidence suggests that changes in the volume of the choroid plexus may be associated with glymphatic system function. Therefore, this study aimed to investigate alterations in choroid plexus volume in patients with migraines compared with healthy controls.

We enrolled 59 patients with migraines (39 and 20 with episodic and chronic migraines, respectively) and 61 healthy controls. All participants underwent brain magnetic resonance imaging, including three-dimensional T1-weighted imaging. We analyzed and compared choroid plexus volumes between patients with episodic migraines, those with chronic migraines and healthy controls. Additionally, we evaluated the association between choroid plexus volume and the clinical characteristics of patients with migraine.

The choroid plexus volume in patients with chronic migraines was higher than that in healthy controls (2.018 vs. 1.698%, p = 0.002) and patients with episodic migraines (2.018 vs. 1.680%, p = 0.010). However, no differences were observed in choroid plexus volumes between patients with episodic migraine and healthy controls. Choroid plexus volume was positively correlated with age in patients with migraines (r = 0.301, p = 0.020) and in healthy controls (r = 0.382, p = 0.002).

We demonstrated significant enlargement of the choroid plexus in patients with chronic migraine compared with healthy controls and those with episodic migraine. This finding suggests that chronic migraine may be associated with glymphatic system dysfunction.

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.

Reading difficulties (RD) frequently co-occur with attention-deficit/hyperactivity disorder (ADHD), and children with both RD + ADHD often demonstrate greater challenges in reading and executive functions (EF) than those with RD-only.

This study examined the effect of a 4-week EF-based reading intervention on behavioral and neurobiological correlates of EF among 8–12 y.o. English-speaking children with RD + ADHD (n = 19), RD-only (n = 18), and typically developing children (n = 18). Behavioral and resting-state fMRI data were collected from all participants before and after 4 weeks of the EF-based reading computerized program. Group (RD + ADHD, RD-only, typical readers) x Test (pre- and post-intervention) repeated measures ANOVAs were conducted for reading, EF, and brain functional connectivity (FC) measures.

Across groups, reading (fluency, comprehension) and EF (inhibition, speed of processing) behavioral performance improved following the intervention. Exploratory subgroup comparisons revealed that children with RD + ADHD, but not RD-only, showed significant gains in reading comprehension, whereas inhibition improved in both RD groups, but not among typical readers. Furthermore, across groups, FC between the frontoparietal (FP) and cingulo-opercular (CO) networks decreased following the intervention. Exploratory subgroup comparisons revealed that children with RD + ADHD, but not RD-only, showed a significant decrease in FC of FP-CO and FP-dorsal attention network.

These results support the differential response to an EF-based reading intervention of children with RD with and without comorbid ADHD at brain and behavioral levels.