Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis.

Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.

Brains of endurance athletes differ in the association areas but not in the primary areas.

Regular participation in sports results in a series of physiological adaptations. However, little is known about the brain adaptations to physical activity. Here we aimed to investigate whether young endurance athletes and non-athletes differ in the gray and white matter of the brain and whether cardiorespiratory fitness (CRF) is associated with these differences. We assessed the CRF, volumes of the gray and white matter of the brain using structural magnetic resonance imaging (sMRI), and brain white matter connections using diffusion magnetic resonance imaging (dMRI) in 20 young male endurance athletes and 21 healthy non-athletes. While total brain volume was similar in both groups, the white matter volume was larger and the gray matter volume was smaller in the athletes compared to non-athletes. The reduction of gray matter was located in the association areas of the brain that are specialized in processing of sensory stimuli. In the microstructure analysis, significant group differences were found only in the association tracts, for example, the inferior occipito-frontal fascicle (IOFF) showing higher fractional anisotropy and lower radial diffusivity, indicating stronger myelination in this tract. Additionally, gray and white matter brain volumes, as well as association tracts correlated with CRF. No changes were observed in other brain areas or tracts. In summary, the brain signature of the endurance athlete is characterized by changes in the integration of sensory and motor information in the association areas.

Imaging the human brain on oral contraceptives: A review of structural imaging methods and implications for future research goals.

Worldwide over 150 million women use oral contraceptives (OCs), which are the most prescribed form of contraception in both the United States and in European countries. Sex hormones, such as estradiol and progesterone, are important endogenous hormones known for shaping the brain across the life span. Synthetic hormones, which are present in OCs, interfere with the natural hormonal balance by reducing the endogenous hormone levels. Little is known how this affects the brain, especially during the most vulnerable times of brain maturation. Here, we review studies that investigate differences in brain gray and white matter in women using OCs in comparison to naturally cycling women. We focus on two neuroimaging methods used to quantify structural gray and white matter changes, namely structural MRI and diffusion MRI. Finally, we discuss the potential of these imaging techniques to advance knowledge about the effects of OCs on the brain and wellbeing in women.

A preliminary choroid plexus volumetric study in individuals with psychosis.

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.

Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05 ± 5.7 years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FAt ), radial diffusivity (RDt ), and axial diffusivity (ADt ). Lower ratings of interindividual pain intensity correlated with higher FAt and lower RDt of the MFB. As changes in FAt and RDt may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.

The social brain network in 22q11.2 deletion syndrome: a diffusion tensor imaging study.

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls. RESULTS: Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis. CONCLUSIONS: Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS.

Diffusion imaging of mild traumatic brain injury in the impact accelerated rodent model: A pilot study.

PRIMARY OBJECTIVE: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. RESEARCH DESIGN: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls. Seven days post injury, DTI was acquired from fixed rat brains using a 7T scanner. Group comparison of Fractional Anisotropy (FA) values between traumatized and sham animals was performed using Tract-Based Spatial Statistics (TBSS), a method that we adapted for rats. MAIN OUTCOMES AND RESULTS: TBSS revealed white matter regions of the brain with increased FA values in the traumatized versus sham rats, localized mainly to the contrecoup region. Regions of increased FA included the pyramidal tract, the cerebral peduncle, the superior cerebellar peduncle and to a lesser extent the fibre tracts of the corpus callosum, the anterior commissure, the fimbria of the hippocampus, the fornix, the medial forebrain bundle and the optic chiasm. CONCLUSION: Seven days post injury, during the period of tissue reparation in the impact acceleration rat model of mTBI, microstructural changes to white matter can be detected using DTI.

Proceedings of the workshop on Cerebellum, Basal Ganglia and Cortical Connections Unmasked in Health and Disorder held in Brno, Czech Republic, October 17th, 2013.

The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). The contributions from individual distinguished speakers cover the neuroanatomical research of complex networks, neuroimaging data showing that the cerebellum and BG are connected to a wide range of other central nervous system structures involved in movement control. Especially, the cerebellum plays a more complex role in how the brain functions than previously thought.

Abnormalities in myelination of the superior cerebellar peduncle in patients with schizophrenia and deficits in movement sequencing.

Deficits in the execution of a sequence of movements are common in schizophrenia. Previous studies reported reduced functional activity in the motor cortex and cerebellum in schizophrenic patients with deficits in movement sequencing. The corticospinal tract (CST) and superior cerebellar peduncle (SCP) are fiber tracts that are involved in movement sequencing. However, the integrity of these tracts has not been evaluated in schizophrenic patients with respect to the performance of movement sequencing yet. Diffusion tensor magnetic resonance images (DT-MRI) were acquired from 24 patients with schizophrenia and 23 matched control subjects. Tractography was applied to reconstruct the CST and SCP and DT-MRI-specific parameters such as fractional anisotropy (FA) and radial diffusivity (RD) were reported. The patient group was further subdivided based on the score of sequencing of complex motor acts subscale of the Neurological Evaluation Scale into those with deficits in sequencing motor acts, the SQ(abn) group (n = 7), and those with normal performance, the SQ(norm) group (n = 17). Schizophrenia patients of the SQ(norm) subgroup had significantly reduced FA and increased RD values in the right CST in comparison to the control group; the SQ(abn) subgroup did not differ from the controls. However, the SQ(abn) subgroup showed impaired integrity of the left SCP, whereas the SQ(norm) subgroup did not. Abnormalities in the right CST in the SQ(norm) and in the left SCP in SQ(abn) groups suggest that the patients with SQ(abn) represent subgroups with distinct deficits. Moreover, these results demonstrate the involvement of the SCP in the pathogenesis of movement sequencing in schizophrenia.

Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19.

Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.

From 'mental fog' to post-acute COVID-19 syndrome's executive function alteration: Implications for clinical approach.

A common symptom of the neuropsychiatric Post-Acute COVID-19 syndrome (neuro-PACS) is the so called 'brain fog'. Patients describe the brain fog as problems with attention, memory and mental fatigue. Brain fog is experienced by 9-55% of people for months after having contracted SARS-CoV-2 virus. Several theories have been proposed to explain PACS's brain fog, including a neuroinflammatory hypothesis, but the hypothesis remains to be proven. Here, we examined inflammatory and immunological blood profile in a cohort of patients with PACS to investigate the association between executive functions and blood inflammatory markers. Executive function was assessed by the Trail Making Test (TMT) Part A and Part B, as well as the Barkley Deficits in Executive Functioning Scale (BDEFS), in 71 patients (36 men), average age of 40 years (range: 15-82, SD: 15.7). Impairment in executive functioning (BDEFS scores and TMT B scores) correlated with increased levels of Interleukin-6 (IL-6), fibrinogen and ferritin. Moreover, elevated levels of Il-6, fibrinogen, ferritin, tumor necrosis factor-alpha and C-reactive protein have been observed in PACS. These findings demonstrate that PACS is characterized by the presence of an immuno-inflammatory process, which is associated with diminished executive functioning. Here, we argue in favour of a shift from the non-descriptive definition of 'mental fog' to a characterization of a subtype of PACS, associated with alteration in executive functioning. Implication for clinical settings and prevention are discussed.

Central autonomic network alterations in male endurance athletes.

Physical exercise causes marked adjustments in brain function and the cardiovascular system. Brain regions of the so-called central autonomic network (CAN) are likely to show exercise-related alterations due to their involvement in cardiac control, yet exercise-induced CAN changes remain unclear. Here we investigate the effects of intensive exercise on brain regions involved in cardiac autonomic regulation using resting-state functional connectivity (rsFC). We explored rsFC of six core regions within CAN, namely ventromedial prefrontal cortex, dorsolateral anterior cingulate cortex, left/right amygdala, and left/right anterior insula, in 20 endurance athletes and 21 non-athletes. We showed that athletes had enhanced rsFC within CAN and sensorimotor areas compared to non-athletes. Likewise, we identified two networks with increased rsFC encompassing autonomic and motor-related areas using network-based statistics analysis. In addition, rsFC displayed an inverse relationship with heart rate, where the stronger rsFC in athletes correlates with their slower heart rate. Despite this significant relationship, mediation analysis revealed that heart rate is a weak mediator of the effect of intensive physical training on rsFC. Our findings prove that physical exercise enhances brain connectivity in central autonomic and sensorimotor networks and highlight the close link between brain and heart.

Larger gray matter volumes in neuropsychiatric long-COVID syndrome.

Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID. To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed. Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found. GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms.

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study.

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

Emotional Awareness in Schizophrenia Is Associated With Gray Matter Volume of Right Precuneus.

Objectives: We assessed the relationship between emotional awareness (e.g., the ability to identify and differentiate our own feelings and feelings of others) and regional brain volumes in healthy and in schizophrenia groups. Methods: Magnetic resonance images of 29 subjects with schizophrenia and 33 matched healthy controls were acquired. Brain gray matter was parcellated using FreeSurfer and 28 regions of interest associated with emotional awareness were analyzed. All participants were assessed using the Levels of Emotional Awareness Scale (LEAS) of Self and of Other. LEAS scores were correlated with gray matter volume for each hemisphere on the 14 brain regions of the emotional awareness network. Results: Individuals with schizophrenia showed decreased emotional awareness on both LEAS Self and LEAS Other compared to healthy controls. There were no statistically significant between-group differences in gray matter volumes of the emotional awareness network. The performance on LEAS Other correlated negatively with right precuneus gray matter volume only in the schizophrenia group. Conclusion: Our findings suggest a relationship between gray matter volume of the right precuneus and deficits in understanding of emotional states of others in schizophrenia.

Smaller subcortical volumes and enlarged lateral ventricles are associated with higher global functioning in young adults with 22q11.2 deletion syndrome with prodromal symptoms of schizophrenia.

The 22q11.2 deletion syndrome (22q11DS) is a developmental genetic syndrome associated with a 30% risk for developing schizophrenia. Lateral ventricles and subcortical structures are abnormal in this syndrome as well as in schizophrenia. Here, we investigated whether these structures are related in young adults with 22q11DS with and without prodromal symptoms (PS) for schizophrenia and whether abnormalities in volumes are associated with global functioning. MR images were acquired on a 3T scanner from 51 individuals with 22q11DS and 30 healthy controls (mean age: 21±2 years). Correlations were performed to evaluate the relationship between ventricular and subcortical volumes, with Global Assessment of Functioning (GAF) and Premorbid Adjustment Scale (PAS) in each group. Lateral ventricular volumes correlated negatively with subcortical volumes in individuals with 22q11DS. In individuals with 22q11DS with PS only, GAF correlated positively with volumes of the lateral ventricles and negatively with subcortical volumes. PAS correlated negatively with lateral ventricle volumes, and positively with volumes of subcortical structures. The results suggest a common neurodevelopmental mechanism related to the growth of these brain structures. Further, the ratio between the volumes and clinical measures could potentially be used to characterize individuals with 22q11DS and those from the general population for the risk of the development of schizophrenia.

Abnormalities in white matter tracts in the fronto-striatal-thalamic circuit are associated with verbal performance in 22q11.2DS.

BACKGROUND: Abnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating 22q11.2 deletion syndrome (22q11DS), a genetic syndrome associated with a 30% risk for developing schizophrenia in adulthood and a decline in Verbal IQ (VIQ) preceding psychosis onset. Here, we examined white matter (WM) tracts in FST sub-circuits, especially those in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC) sub-circuits, and their associations with VIQ in young adults with 22q11DS. METHODS: Diffusion MRI scans were acquired from 21 individuals with 22q11DS with prodromal symptoms of schizophrenia, 30 individuals with 22q11DS without prodromal symptoms, and 30 healthy controls (mean age: 21 ± 2 years). WM tracts were reconstructed between striatum and thalamus with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. Fractional anisotropy (FA) and radial diffusivity (RD) were used for group comparisons. VIQ was assessed and associations with the diffusion measures were evaluated. RESULTS: FA was significantly increased and RD decreased in most tracts of the DLPFC and VLPFC sub-circuits in 22q11DS. Verbal IQ scores correlated negatively with FA and, at trend level, positively with RD in the right thalamus-IFG tract in 22q11DS with prodromal symptoms. CONCLUSIONS: While abnormalities in FST sub-circuits are associated with schizophrenia, we observed that these abnormalities are also present in 22q11DS individuals with prodromal symptoms and are associated with verbal performance in the right thalamus-IFG tract.

Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 Deletion Syndrome (22q11DS) is a genetic, neurodevelopmental disorder characterized by a chromosomal deletion and a distinct cognitive profile. Although abnormalities in the macrostructure of the cortex have been identified in individuals with 22q11DS, it is not known if there are additional microstructural changes in gray matter regions in this syndrome, and/or if such microstructural changes are associated with cognitive functioning. METHODS: This study employed a novel diffusion MRI measure, the Heterogeneity of Fractional Anisotropy (HFA), to examine variability in the microstructural organization of the cortex in healthy young adults (N = 30) and those with 22q11DS (N = 56). Diffusion MRI, structural MRI, clinical and cognitive data were acquired. RESULTS: Compared to controls, individuals with 22q11DS evinced increased HFA in cortical association (p = .003, d = 0.86) and paralimbic (p < .0001, d = 1.2) brain areas, whereas no significant differences were found between the two groups in primary cortical brain areas. Additionally, increased HFA of the right paralimbic area was associated with poorer performance on tests of response inhibition, i.e., the Stroop Test (rho = -0.37 p = .005) and the Gordon Diagnostic System Vigilance Commission (rho = -0.41 p = .002) in the 22q11DS group. No significant correlations were found between HFA and cognitive abilities in the healthy control group. CONCLUSIONS: These findings suggest that cortical microstructural disorganization may be a neural correlate of response inhibition in individuals with 22q11DS. Given that the migration pattern of neural crest cells is disrupted at the time of early brain development in 22q11DS, we hypothesize that these neural alterations may be neurodevelopmental in origin, and reflect cortical dysfunction associated with cognitive deficits.

Diffusion abnormalities in the corpus callosum in first episode schizophrenia: Associated with enlarged lateral ventricles and symptomatology.

INTRODUCTION: Abnormalities in the corpus callosum (CC) and the lateral ventricles (LV) are hallmark features of schizophrenia. These abnormalities have been reported in chronic and in first episode schizophrenia (FESZ). Here we explore further associations between CC and LV in FESZ using diffusion tensor imaging (DTI). METHODS: . Sixteen FESZ patients and 16 healthy controls (HC), matched on age, gender, and handedness participated in the study. Diffusion and structural imaging scans were acquired on a 3T GE Signa magnet. Volumetric measures for LV and DTI measures for five CC subdivisions were completed in both groups. In addition, two-tensor tractography, the latter corrected for free-water (FAt), was completed for CC. Correlations between LV and DTI measures of the CC were examined in both groups, while correlations between DTI and clinical measures were examined in only FESZ. RESULTS: Results from two-tensor tractography demonstrated decreased FAt and increased trace and radial diffusivity (RDt) in the five CC subdivisions in FESZ compared to HC. Central CC diffusion measures in FESZ were significantly correlated with volume of the LV, i.e., decreased FAt values were associated with larger LV volume, while increased RDt and trace values were associated with larger LV volume. In controls, correlations were also significant, but they were in the opposite direction from FESZ. In addition, decreased FAt in FESZ was associated with more positive symptoms. DISCUSSION: Partial volume corrected FAt, RDt, and trace abnormalities in the CC in FESZ suggest possible de- or dys-myelination, or changes in axonal diameters, all compatible with neurodevelopmental theories of schizophrenia. Correlational findings between the volume of LV and diffusion measures in FESZ reinforce the concept of a link between abnormalities in the LV and CC in early stages of schizophrenia and are also compatible with neurodevelopmental abnormalities in this population.

Childhood adversity associated with white matter alteration in the corpus callosum, corona radiata, and uncinate fasciculus of psychiatrically healthy adults.

Diffusion tensor imaging studies report childhood adversity (CA) is associated with reduced fractional anisotropy (FA) in multiple white matter tracts in adults. Reduced FA may result from changes in tissue, suggesting myelin/axonal damage, and/or from increased levels of extracellular free-water, suggesting atrophy or neuroinflammation. Free-water imaging can separately identify FA in tissue (FAT) and the fractional volume of free-water (FW). We tested whether CA was associated with altered FA, FAT, and FW in seven white matter regions of interest (ROI), in which FA changes had been previously linked to CA (corona radiata, corpus callosum, fornix, cingulum bundle: hippocampal projection, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus). Tract-based spatial statistics were performed in 147 psychiatrically healthy adults who had completed a self-report questionnaire on CA primarily stemming from parental maltreatment. ROI were extracted according to the protocol provided by the ENIGMA-DTI working group. Analyses were performed both treating CA as a continuous and a categorical variable. CA was associated with reduced FA in all ROI (although categorical analyses failed to find an association in the fornix). In contrast, CA was only associated with reduced FAT in the corona radiata, corpus callosum, and uncinate fasciculus (with the continuous measure of CA finding evidence of a negative relation between CA and FAT in the fornix). There was no association between CA on FW in any ROI. These results provide preliminary evidence that childhood adversity is associated with changes to the microstructure of white matter itself in adulthood. However, these results should be treated with caution until they can be replicated by future studies which address the limitations of the present study.