The choroid plexus (ChP) is part of the blood‐cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered ...essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging‐based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87). We further showed a significant ChP volume increase in early psychosis (left: p < .00010, right: p < .00010) and a significant positive correlation between higher ChP and higher LV volumes in chronic psychosis (left: r = .54, p = .0030, right: r = .68; p < .0010). Our study suggests that ChP enlargement may be a marker of acute response around disease onset. It might also play a modulatory role in the chronic enlargement of lateral ventricles, often reported in psychosis. Future longitudinal studies should investigate the dynamics of ChP enlargement as a promising marker for novel therapeutic strategies.
The choroid plexus (ChP) plays an essential role in psychosis but is challenging to study in vivo. Here, we develop a novel magnetic resonance imaging‐based segmentation method to examine ChP volumes in individuals with psychosis. Our findings suggest that ChP enlargements may be a marker of acute response around disease onset and might play a modulatory role in the chronic enlargement of lateral ventricles.
Diffusion MRI studies consistently report group differences in white matter between individuals diagnosed with schizophrenia and healthy controls. Nevertheless, the abnormalities found at the ...group‐level are often not observed at the individual level. Among the different approaches aiming to study white matter abnormalities at the subject level, normative modeling analysis takes a step towards subject‐level predictions by identifying affected brain locations in individual subjects based on extreme deviations from a normative range. Here, we leveraged a large harmonized diffusion MRI dataset from 512 healthy controls and 601 individuals diagnosed with schizophrenia, to study whether normative modeling can improve subject‐level predictions from a binary classifier. To this aim, individual deviations from a normative model of standard (fractional anisotropy) and advanced (free‐water) dMRI measures, were calculated by means of age and sex‐adjusted z‐scores relative to control data, in 18 white matter regions. Even though larger effect sizes are found when testing for group differences in z‐scores than are found with raw values (p < .001), predictions based on summary z‐score measures achieved low predictive power (AUC < 0.63). Instead, we find that combining information from the different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance (the best predictor achieved AUC = 0.726). Our findings suggest that extreme deviations from a normative model are not optimal features for prediction. However, including the complete distribution of deviations across multiple imaging measures improves prediction, and could aid in subject‐level classification.
We use a large (n = 1113) harmonized diffusion MRI dataset of individuals diagnosed with schizophrenia and healthy controls, in order to study the predictive performance of a normative modeling approach. This approach compares each individual with distribution derived from healthy controls to derive measures of deviation from the normal distribution. Our results show that combining deviation information from different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance, and could therefore aid in subject‐level classification.
Objective
To investigate how the presence/side of hippocampal sclerosis (HS) are related to the white matter structure of cingulum bundle (CB), arcuate fasciculus (AF), and inferior longitudinal ...fasciculus (ILF) in mesial temporal lobe epilepsy (MTLE).
Methods
We acquired diffusion‐weighted magnetic resonance imaging (MRI) from 86 healthy and 71 individuals with MTLE (22 righ‐HS; right‐HS, 34 left‐HS; left‐HS, and 15 nonlesional MTLE). We utilized two‐tensor tractography and fiber clustering to compare fractional anisotropy (FA) of each side/tract between groups. Additionally, we examined the association between FA and nonverbal (WMS‐R) and verbal (WMS‐R, RAVLT codification) memory performance for MTLE individuals.
Results
White matter abnormalities depended on the side and presence of HS. The left‐HS demonstrated widespread abnormalities for all tracts, the right‐HS showed lower FA for ipsilateral tracts and the nonlesional MTLE group did not differ from healthy individuals. Results indicate no differences in verbal/nonverbal memory performance between the groups, but trend‐level associations between higher FA of visual memory and the left CB (r = 0.286, P = 0.018), verbal memory (RAVLT) and ‐left CB (r = 0.335, P = 0.005), ‐right CB (r = 0.286, P = 0.016), and ‐left AF (r = 0.287, P = 0.017).
Significance
Our results highlight that the presence and side of HS are crucial to understand the pathophysiology of MTLE. Specifically, left‐sided HS seems to be related to widespread bilateral white matter abnormalities. Future longitudinal studies should focus on developing diagnostic and treatment strategies dependent on HS's presence/side.
White matter (WM) abnormalities are repeatedly demonstrated across the schizophrenia time-course. However, our understanding of how demographic and clinical variables interact, influence, or are ...dependent on WM pathologies is limited. The most well-known barriers to progress are heterogeneous findings due to small sample sizes and the confounding influence of age on WM. The present study leverages access to the harmonized diffusion magnetic-resonance-imaging data and standardized clinical data from 13 international sites (597 schizophrenia patients (SCZ)). Fractional anisotropy (FA) values for all major WM structures in patients were predicted based on FA models estimated from a healthy population (n = 492). We utilized the deviations between predicted and real FA values to answer three essential questions. (1) "Which clinical variables explain WM abnormalities?". (2) "Does the degree of WM abnormalities predict symptom severity?". (3) "Does sex influence any of those relationships?". Regression and mediator analyses revealed that a longer duration-of-illness is associated with more severe WM abnormalities in several tracts. In addition, they demonstrated that a higher antipsychotic medication dose is related to more severe corpus callosum abnormalities. A structural equation model revealed that patients with more WM abnormalities display higher symptom severity. Last, the results exhibited sex-specificity. Males showed a stronger association between duration-of-illness and WM abnormalities. Females presented a stronger association between WM abnormalities and symptom severity, with IQ impacting this relationship. Our findings provide clear evidence for the interaction of demographic, clinical, and behavioral variables with WM pathology in SCZ. Our results also point to the need for longitudinal studies, directly investigating the casualty and sex-specificity of these relationships, as well as the impact of cognitive resiliency on structure-function relationships.
Background Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), ...depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration. Methods Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA. Results Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex ( r = 0.400, p = 0.005). Conclusion Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.
Deletions and duplications at the 22q11.2 locus are associated with significant neurodevelopmental and psychiatric morbidity. Previous diffusion-weighted magnetic resonance imaging (MRI) studies in ...22q11.2 deletion carriers (22q-del) found nonspecific white matter (WM) abnormalities, characterized by higher fractional anisotropy. Here, utilizing novel imaging and processing methods that allow separation of signal contribution from different tissue properties, we investigate whether higher anisotropy is driven by (1) extracellular changes, (2) selective degeneration of secondary fibers, or (3) volumetric differences. We further, for the first time, investigate WM microstructure in 22q11.2 duplication carriers (22q-dup). Multi-shell diffusion-weighted images were acquired from 26 22q-del, 19 22q-dup, and 18 healthy individuals (HC). Images were fitted with the free-water model to estimate anisotropy following extracellular free-water elimination and with the novel BedpostX model to estimate fractional volumes of primary and secondary fiber populations. Outcome measures were compared between groups, with and without correction for WM and cerebrospinal fluid (CSF) volumes. In 22q-del, anisotropy following free-water elimination remained significantly higher compared with controls. BedpostX did not identify selective secondary fiber degeneration. Higher anisotropy diminished when correcting for the higher CSF and lower WM volumes. In contrast, 22q-dup had lower anisotropy and greater extracellular space than HC, not influenced by macrostructural volumes. Our findings demonstrate opposing effects of reciprocal 22q11.2 copy-number variation on WM, which may arise from distinct pathologies. In 22q-del, microstructural abnormalities may be secondary to enlarged CSF space and more densely packed WM. In 22q-dup, we see evidence for demyelination similar to what is commonly observed in neuropsychiatric disorders.
The imaging-based method of brainAGE aims to characterize an individual’s vulnerability to age-related brain changes. The present study systematically reviewed brainAGE findings in neuropsychiatric ...conditions and discussed the potential of brainAGE as a marker for biological age. A systematic PubMed search (from inception to March 6th, 2023) identified 273 articles. The 30 included studies compared brainAGE between neuropsychiatric and healthy groups (n≥50). We presented results qualitatively and adapted a bias risk assessment questionnaire. The imaging modalities, design, and input features varied considerably between studies. While the studies found higher brainAGE in neuropsychiatric conditions (11 mild cognitive impairment/ dementia, 11 schizophrenia spectrum/ other psychotic and bipolar disorder, six depression/ anxiety, two multiple groups), the associations with clinical characteristics were mixed. While brainAGE is sensitive to group differences, limitations include the lack of diverse training samples, multi-modal studies, and external validation. Only a few studies obtained longitudinal data, and all have used algorithms built solely to predict chronological age. These limitations impede the validity of brainAGE as a biological age marker.
•BrainAGE measures can be derived from neuroimaging data using machine learning.•BrainAGE is higher in neuropsychiatric populations than in healthy individuals.•Limitations include the lack of diverse samples, multi-modal studies, and validation.•The lack of longitudinal models restricts the validity of brainAGE as a marker of biological age.
The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is ...associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.
Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) ...microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (
= 38), (2) mTBI (
= 25), (3) comorbid PTSD+mTBI (
= 94), and (4) a control group with neither PTSD nor mTBI (
= 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (
= 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (
< 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (
< 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.
The geroscience hypothesis asserts that physiological aging is caused by a small number of biological pathways. Despite the explosion of geroscience research over the past couple of decades, the ...research on how serious mental illnesses (SMI) affects the biological aging processes is still in its infancy. In this review, we aim to provide a critical appraisal of the emerging literature focusing on how we measure biological aging systematically, and in the brain and how SMIs affect biological aging measures in older adults. We will also review recent developments in the field of cellular senescence and potential targets for interventions for SMIs in older adults, based on the geroscience hypothesis.
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