Matter Microstructure In Adolescents Research Articles

Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents

Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13–15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.

Beyond BMI: cardiometabolic measures as predictors of impulsivity and white matter changes in adolescents

Obesity is characterized by cardiometabolic and neurocognitive changes. However, how these two factors relate to each other in this population is unknown. We tested the association that cardiometabolic measures may have with impulse behaviors and white matter microstructure in adolescents with and without an excess weight. One hundred and eight adolescents (43 normal-weight and 65 overweight/obesity; 11–19 years old) were medically and psychologically (Temperament Character Inventory Revised, Three-Factor Eating Questionnaire-R18, Conners’ Continuous Performance Test-II, Stroop Color and Word Test, Wisconsin Card Sorting Test, Kirby Delay Discounting Task) evaluated. A subsample of participants (n = 56) underwent a brain magnetic resonance imaging acquisition. In adolescents, higher triglycerides and having a body mass index indicative of overweight/obesity predicted a more impulsive performance in Conners’ Continuous Performance Test-II (higher commission errors). In addition, higher glucose and diastolic blood pressure values predicted increments in the Three-Factor Eating Questionnaire-R18 emotional eating scale. Neuroanatomically, cingulum fractional anisotropy showed a negative relationship with glycated hemoglobin. The evaluation of the neurocognitive differences associated with obesity, usually based on body mass index, should be complemented with cardiometabolic measures.

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen’s d = 0.37), posterior corona radiata (d = 0.32), and superior fronto‐occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.

Resting Oxygen Saturations are Associated With Altered Brain White Matter Microstructure in Adolescents and Adults With a Fontan Circulation; A Diffusion Brain MRI Study

Long-term cognitive dysfunction is common in people with a Fontan circulation, however underlying brain alterations associated with worse outcomes are poorly characterised. Chronic hypoxaemia is also common and is associated with long-term morbidity and mortality. This study investigated brain white matter (WM) microstructure in adolescents and adults with a Fontan circulation and associations with resting oxygen saturations (SaO2) and cognitive functioning.

A diffusion MRI study of brain white matter microstructure in adolescents and adults with a Fontan circulation: Investigating associations with resting and peak exercise oxygen saturations and cognition

IntroductionAdolescents and adults with a Fontan circulation are at risk of cognitive dysfunction; Attention and processing speed are notable areas of concern. Underlying mechanisms and brain alterations associated with worse long-term cognitive outcomes are not well determined. This study investigated brain white matter microstructure in adolescents and adults with a Fontan circulation and associations with resting and peak exercise oxygen saturations (SaO2), predicted maximal oxygen uptake during exercise (% pred VO2), and attention and processing speed. MethodsNinety-two participants with a Fontan circulation (aged 13–49 years, ≥5 years post-Fontan completion) had diffusion MRI. Averaged tract-wise diffusion tensor imaging (DTI) metrics were generated for 34 white matter tracts of interest. Resting and peak exercise SaO2 and % pred VO2 were measured during cardiopulmonary exercise testing (CPET; N = 81). Attention and processing speed were assessed using Cogstate (N = 67 and 70, respectively). Linear regression analyses adjusted for age, sex, and intracranial volume were performed to investigate associations between i) tract-specific DTI metrics and CPET variables, and ii) tract-specific DTI metrics and attention and processing speed z-scores. ResultsForty-nine participants were male (53%), mean age was 23.1 years (standard deviation (SD) = 7.8 years). Mean resting and peak exercise SaO2 were 93.1% (SD = 3.6) and 90.1% (SD = 4.7), respectively. Mean attention and processing speed z-scores were −0.63 (SD = 1.07) and −0.72 (SD = 1.44), respectively. Resting SaO2 were positively associated with mean fractional anisotropy (FA) of the left corticospinal tract (CST) and right superior longitudinal fasciculus I (SLF-I) and negatively associated with mean diffusivity (MD) and radial diffusivity (RD) of the right SLF-I (p ≤ 0.01). Peak exercise SaO2 were positively associated with mean FA of the left CST and were negatively associated with mean RD of the left CST, MD of the left frontopontine tract, MD, RD and axial diffusivity (AD) of the right SLF-I, RD of the left SLF-II, MD, RD and AD of the right SLF-II, and MD and RD of the right SLF–III (p ≤ 0.01). Percent predicted VO2 was positively associated with FA of the left uncinate fasciculus (p < 0.01). Negative associations were identified between mean FA of the right arcuate fasciculus, right SLF-II and right SLF-III and processing speed (p ≤ 0.01). No significant associations were identified between DTI-based metrics and attention. ConclusionChronic hypoxemia may have long-term detrimental impact on white matter microstructure in people living with a Fontan circulation. Paradoxical associations between processing speed and tract-specific DTI metrics could be suggestive of compensatory white matter remodeling. Longitudinal investigations focused on the mechanisms and trajectory of altered white matter microstructure and associated cognitive dysfunction in people with a Fontan circulation are required to better understand causal associations.

Inflammatory cytokines and callosal white matter microstructure in adolescents

Adolescent depression is characterized by heightened inflammation and altered connectivity of fronto-cingulate-limbic tracts, including the genu of the corpus callosum (CCG) and the uncinate fasciculus (UF). No studies, however, have yet examined the association between inflammation, measured by peripheral levels of cytokines, and white matter connectivity of fronto-cingulate-limbic tracts in adolescents. Here, 56 depressed adolescents (32 females, 3 non-binary; 16.23 ± 1.28 years) and 19 controls (10 females; 15.72 ± 1.17 years) completed a diffusion-weighted MRI scan at 3 Tesla. We conducted deterministic tractography to segment bilateral corpus callosum (genu and splenium) and UF and computed mean fractional anisotropy (FA) in each tract. A subset of participants (43 depressed and 17 healthy controls) also provided dried blood spot samples from which we assayed interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-ɑ) using a Luminex multiplex array. Depressed participants did not differ from controls in FA of the corpus callosum or UF (all FDR-corrected ps > 0.056) but exhibited higher levels of inflammation than did controls (IL-6: β = 0.91, FDR-corrected p = 0.006; TNF-α: β = 0.76, FDR-corrected p = 0.006). Although diagnostic group did not moderate the associations between inflammatory cytokines and FA in the CCG and UF, across both groups, greater peripheral inflammation was associated with lower FA in the CCG (IL-6: β = −0.38; FDR-corrected p = 0.044; TNF-ɑ: β = −0.41, FDR-corrected p = 0.044). This study is the first to examine associations between peripheral inflammation and white matter microstructure of fronto-cingulate-limbic tracts in depressed and nondepressed adolescents. Future mechanistic studies are needed to confirm our findings; nevertheless, our results suggest that heightened inflammation is an important component of neurophenotypes that are relevant to adolescent depression.

Sex-specific associations between early-life exposure to manganese and white matter microstructure in adolescents and young adults

Background: The brain white matter (WM) connects gray matter regions into functional networks and is critical for human cognition and behavior. Early-life metal exposure can disrupt WM maturation and lead to long-lasting changes in neuronal circuitry. Despite a growing literature suggesting associations between environmental levels of metal exposures and persistent neurodevelopmental effects, the underlying brain mechanisms of these associations are poorly understood. Furthermore, the influence of sex on these associations is understudied. The goal of the present study was to examine sex-specific associations between early-life exposure to manganese (Mn) and WM microstructure in young adults. Methods: Participants are adolescents and young adults enrolled in the ongoing Public Health Impact of Manganese Exposure (PHIME) study. Fractional anisotropy (FA) measures from diffusion tensor imaging (DTI) were acquired from 73 participants (16-23 years; 39 females) in a 3T Siemens scanner. Prenatal, early postnatal and childhood Mn concentrations were measured in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We generated an FA index (representing a combination of FA in 48 brain regions of the ICBM-DTI-81 atlas) using weighted quantile sum (WQS) regression and investigated associations between the FA index and Mn at each timepoint, controlling for socioeconomic status, sex, and age. To test our hypothesis that sex has a moderating effect on the association between early life Mn exposure and WM integrity, we included an interaction term between sex and Mn. Results: The FA index was positively associated with dentine Mn at all three timepoints. This association was driven by FA in the fornix, cerebral pedencule, tapetum and superior longitudinal fasciculus. Associations were stronger in males. Conclusion: These results suggest that a) early-life Mn exposure is associated with WM microstructure within regions involved in widespread motor and cognitive functions, and b) the effect of Mn exposure on the brain differs by sex.

White Matter Microstructure in Adolescents and Young Adults With Non-Suicidal Self-Injury.

BackgroundNon-suicidal self-injury (NSSI) is a growing public health concern that commonly begins in adolescence, and can persist into young adulthood. A promising approach for advancing our understanding of NSSI in youth is to examine white matter microstructure using diffusion magnetic resonance imaging (dMRI).MethodThe present study examined whole-brain group differences in structural connectivity (as measured by generalized fractional anisotropy [GFA]) between 28 female adolescents and young adults ages 13–21 years with NSSI and 22 age-matched healthy controls (HC). We also explored the association between clinical characteristics including NSSI severity and duration, impulsivity, emotion regulation and personality traits within the NSSI group and GFA of the uncinate fasciculus and cingulum.ResultsCompared to the HC group, participants with NSSI had lower GFA in several white matter tracts, including the uncinate fasciculus, cingulum, bilateral superior and inferior longitudinal fasciculi, anterior thalamic radiation, callosal body, and corticospinal tract. When controlling for depressive symptoms, the NSSI group showed an association between NSSI duration (time since initiating NSSI behavior) and lower GFA in the left cingulum. Higher levels of attentional impulsivity were related to lower GFA in the left uncinate fasciculus within the NSSI group.ConclusionsWe found evidence suggesting widespread white matter microstructure deficits in adolescents and young adults with NSSI versus HC. We also report inverse associations between white matter integrity and clinical characteristics (duration of NSSI and attentional impulsivity). These white matter microstructural deficits may represent a possible neurobiologically-based vulnerability to developing maladaptive coping mechanisms, such as NSSI. Additionally, results suggest that this white matter disorganization may either worsen with prolonged engagement in NSSI or predict persistent NSSI; thereby highlighting the importance of early intervention targeting this behavior.

Differences in attentional control and white matter microstructure in adolescents with attentional, affective, and behavioral disorders.

Adolescence is a critical time of physiological, cognitive, and social development. It is also a time of increased risk-taking and vulnerability for psychopathology. White matter (WM) changes during adolescence have been better elucidated in the last decade, but how WM is impacted by psychopathology during this time remains unclear. Here, we examined the link between WM microstructure and psychopathology during adolescence. Twenty youth diagnosed with affective, attentional, and behavioral disorders (clinical sample), and 20 age-matched controls were recruited to examine group differences in WM microstructure, attentional control, and the link between them. The main results showed that clinical sample had relatively lower attentional control and fractional anisotropy (FA) in WM throughout the brain: two association tracts were identified, and many differences were found in areas rich in callosal and projection fibers. Moreover, increased FA was positively associated with attention performance in the clinical sample in structures supporting ventral WM pathways, whereas a similar link was identified in controls in dorsal WM association fibers. Overall, these results support a model of general impairment in WM microstructure combined with reliance on altered, perhaps less efficient, pathways for attentional control in youth with affective, attentional, and behavioral disorders.

White matter microstructure relates to lassitude but not diagnosis in adolescents with depression.

The neurobiology of adolescent depression remains poorly understood. Initial studies suggested impaired white matter microstructure in adults and adolescents, but findings have not been consistent. Challenges in this literature have included small samples, medication confounds and inconsistent correction for type I error. This study addressed these issues in a new examination of fractional anisotropy (FA) in adolescents with major depressive disorder (MDD) using diffusion tensor imaging. We examined FA in 81 adolescents aged 12-19 (44 MDD [all unmedicated], 37 controls). We conducted logistic regression analyses to examine the odds of MDD versus control based on FA within standard white matter tracts that were delineated by probabilistic tractography. We also examined relationships between FA and disease severity (overall depression and dimensions of illness). Finally, we conducted a voxel-wise group comparison of FA. All analyses covaried for age, sex and socioeconomic status, and applied rigorous corrections for multiple testing. Logistic regression did not reveal significant associations between diagnosis and FA within white matter tracts defined by probabilistic tractography. Dimensional analyses revealed that greater lassitude was associated with higher FA in right cingulum bundle and bilateral corticospinal tracts, but with lower FA in right anterior thalamic radiation. Voxel-wise group comparisons of FA did not reveal significant group differences. The current findings do not support low FA as a neurobiological marker of adolescent depression. Dimensional results suggest that FA relates to lassitude but not overall depression. Given the clinical and neurobiological heterogeneity of depression, future work utilizing dimensional approaches may help elucidate the role of white matter microstructure in adolescent depression neurobiology.

Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV.

Rapid maturation of major white matter pathways occurs in the first 2years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2years on neurocognitive functioning and white matter development in adolescence has not been studied. Forty-six adolescents who initiated ART during the first 2years of life (< 2years) and 79 adolescents who initiated ART after 2years of age (> 2years), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) in a region of interest analysis. Neurocognitive performance was similar between adolescents who initiated ART < 2years or > 2years. There was a trend towards attention (p= .07) and working memory (p= .05) being poorer in the group who initiated ART > 2years. FA was lower in the > 2-year group in the superior corona radiata (p= .03), and the external capsule (p= .04). MD was higher in the > 2-year group in the cerebral peduncle (p= .02), the superior corona radiata (p= .01), and the superior fronto-occipital fasciculus (p= .03). RD was higher in the > 2-year group in the superior corona radiata (p= .02), the cerebral peduncle (p= .01), and the superior fronto-occipital fasciculus (p= .01). However, the higher AD in the > 2-year group in the superior corona radiata was not in the expected direction (p= .01). Initiation of ART after the neuronal development period of the second postnatal year is associated with white matter alterations on neuroimaging.

Resilience to Risk for Psychopathology: The Role of White Matter Microstructural Development in Adolescence

BackgroundOne major risk factor for the development of psychopathology is a family history of psychopathology (FHP). Cross-sectional studies have shown that FHP is associated with alterations in white matter microstructure in adolescents without current psychopathology; however, whether these associations persist throughout adolescence, particularly in those who remain resilient to developing psychopathology, is unclear. MethodsSixty-six adolescents underwent diffusion-weighted imaging at baseline (12–16 years of age) and at one or two follow-up visits (142 total scans). Adolescents’ parents completed a modified Family History Assessment Module to calculate FHP density (FHPD) based on familial alcohol use, substance use, and major depressive, generalized anxiety, substance-induced mood, and antisocial personality disorders. The relationship between FHPD and white matter microstructural development was examined using multilevel modeling. ResultsFHPD was associated with significant alterations in white matter microstructure at baseline; in the bilateral superior corona radiata and left superior longitudinal fasciculus, these effects were transient (FHPD was associated with altered white matter microstructure only in early adolescence), while effects in the posterior limb of the internal capsule were persistent. Associations between FHPD and white matter microstructure in the body of the corpus callosum emerged later in adolescence. ConclusionsThis prospective, longitudinal study provides novel information indicating that the association between FHP and white matter microstructure previously observed in adolescents is transient in most regions but may persist into late adolescence in other regions, despite current resilience to developing psychopathology. Future studies are necessary to determine if these persistent alterations are associated with onset of psychopathology later in life.

A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder.

BackgroundThe biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear.MethodsWe used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history.ResultsThe CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone.ConclusionsAdolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM ‘connectivity’.

Altered White Matter Microstructure in Adolescents and Adults with Bulimia Nervosa.

Previous data suggest structural and functional deficits in frontal control circuits in adolescents and adults with bulimia nervosa (BN), but less is known about the microstructure of white matter in these circuits early in the course of the disorder. Diffusion tensor imaging (DTI) data were acquired from 28 female adolescents and adults with BN and 28 age- and BMI-matched healthy female participants. Tract-based spatial statistics (TBSS) was used to detect group differences in white matter microstructure and explore the differential effects of age on white matter microstructure across groups. Significant reductions in fractional anisotropy (FA) were detected in the BN compared with healthy control group in multiple tracts including forceps minor and major, superior longitudinal, inferior fronto-occipital, and uncinate fasciculi, anterior thalamic radiation, cingulum, and corticospinal tract. FA reductions in forceps and frontotemporal tracts correlated inversely with symptom severity and Stroop interference in the BN group. These findings suggest that white matter microstructure is abnormal in BN in tracts extending through frontal and temporoparietal cortices, especially in those with the most severe symptoms. Age-related differences in both FA and RD in these tracts in BN compared with healthy individuals may represent an abnormal trajectory of white matter development that contributes to the persistence of functional impairments in self-regulation in BN.

White matter abnormalities in adolescents with major depressive disorder

The purpose of this study was to identify areas of abnormal white matter microstructure in adolescents with Major Depressive Disorder (MDD) using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values representing preferential diffusivity along major tracts were examined using tract-based spatial statistics across the whole brain in adolescents ages 13-19 with MDD (n = 31) compared with demographically-matched healthy controls (n = 31). We not only examined frontal lobe tracts that have been most frequently identified as abnormal in previous DTI studies of older depressed patients, but also tested for FA group differences across the whole brain to determine if adolescent depression was related to any other regional white matter abnormality. MDD-diagnosed adolescents had significantly lower FA in many regions concentrated predominantly in the frontal lobe. There also was strong evidence for lower FA in bilateral anterior/posterior limbs of the internal capsules, as well as tracts through the midbrain, left external capsule, right thalamic radiation and left inferior longitudinal fasciculus. Consistent with previous findings in depressed young and elderly adults, the current study found evidence for abnormal microstructure in white matter connections of the frontal lobe in MDD adolescents. There also was strong evidence for FA abnormalities in corpus callosum genu, internal and external capsule tracts, thalamus and midbrain, notable for both the relative magnitude of these effects and absence from most previous white matter studies of depression. These abnormalities might represent important markers of early life-onset depression.

Adolescents with d-transposition of the great arteries repaired in early infancy demonstrate reduced white matter microstructure associated with clinical risk factors

Our objective was to use diffusion tensor imaging (DTI) to compare white matter microstructure in adolescents with D-transposition of the great arteries (D-TGA) who underwent the arterial switch operation in early infancy with typically developing control adolescents. We also examined correlates between patient demographic and medical risk factors and white matter as assessed by regional fractional anisotropy (FA) values. We used with magnetic resonance imaging (MRI) to study 49 adolescents with D-TGA and 29 control adolescents. MRI data, including whole brain DTI and conventional anatomic MRI, were acquired from each subject. Each subject's data were analyzed using random effects analysis to evaluate regional white matter differences in FA between D-TGA and control adolescents. While multifocal punctate MRI hypointensities on T1-weighted (T1W) imaging suggestive of mineralization were found, other evidence of gross white matter injury was absent. Eighteen discrete regions of significantly reduced FA in D-TGA adolescents compared with controls were observed in deep white matter of cerebral hemispheres, cerebellum, and midbrain. Among D-TGA adolescents, lower FA correlated with younger gestational age, shorter duration of intraoperative cooling, higher intraoperative minimum tympanic temperature, longer intensive care unit stay after repair, and greater total number of open cardiac operations. Despite scant white matter injury evident on conventional brain MRI, adolescents with D-TGA repaired in infancy demonstrate significant white matter FA reduction that may relate to their reported neurocognitive deficits. Among adolescents with D-TGA, FA values are associated with patient and perioperative factors, some of which are modifiable.

The Impact of Sex, Puberty, and Hormones on White Matter Microstructure in Adolescents

During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. White matter microstructure was examined in 77 adolescents (ages 10-16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids.

Changes in Gray Matter Volume and White Matter Microstructure in Adolescents with Obsessive-Compulsive Disorder

There is a paucity of neuroimaging data in pediatric-onset obsessive-compulsive disorder (OCD). This multimodal neuroimaging study aimed to identify structural gray (GM) and white matter (WM) microstructure changes in pediatric OCD. We obtained structural and diffusion tensor magnetic resonance images from 26 OCD patients and 26 matched healthy adolescents. We carried out a series of image analyses including, volumetric and shape analysis of subcortical gray structures, as well as voxel-based morphometry on GM volume and fractional anisotropy of the WM. Patients had increased GM volume in the caudate bilaterally and right putamen. Shape analyses revealed specific hypertrophy of the dorsal caudate in pediatric OCD. The striatum was larger in healthy boys compared with healthy girls, whereas such a gender effect was not seen in the OCD group. OCD subjects showed higher fractional anisotropy values in left inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, right inferior fronto-occipital fasciculus, bilateral corticospinal tract, corpus callosum splenium and genu, bilateral forceps major, bilateral forceps minor, left cingulum, and right uncinate fasciculus. OCD symptom severity was positively correlated with GM volume in right insula, posterior orbitofrontal cortex, brainstem, and cerebellum and inversely correlated with widespread reduction in cortical GM volume. Furthermore, symptom severity positively correlated with increased WM fractional anisotropy in various WM tracts, including the anterior limb of the internal capsule. Adolescents with OCD had a wide range of GM and WM changes compared to healthy control subjects that are broadly consistent with those identified in the adult OCD literature but are more extensive.

Atypical development of white matter microstructure in adolescents with autism spectrum disorders

Diffusion tensor imaging (DTI) studies in adolescents with autism spectrum disorders (ASD) indicate aberrant neurodevelopment of frontal white matter (WM), potentially underlying abnormal social cognition and communication in ASD. Here, we further use tract-based spatial statistics (TBSS) to examine the developmental change of WM skeleton (i.e., the most compact whole-brain WM) during adolescence in ASD. This whole-brain DTI used TBSS measures fractional anisotropy (FA) and longitudinal and radial diffusivities in fifty adolescents, 25 ASD and 25 controls. Results show that adolescents with ASD versus controls had significantly reduced FA in the right posterior limb of internal capsule (increased radial diffusivity distally and reduced longitudinal diffusivity centrally). Adolescents with ASD versus controls (covarying for age and IQ) had significantly greater FA in the frontal lobe (reduced radial diffusivity), right cingulate gyrus (reduced radial diffusivity), bilateral insula (reduced radial diffusivity and increased longitudinal diffusivity), right superior temporal gyrus (reduced radial diffusivity), and bilateral middle cerebellar peduncle (reduced radial diffusivity). Notably, a significant interaction with age by group was found in the right paracentral lobule and bilateral superior frontal gyrus as indicated by an age-related FA gain in the controls whilst an age-related FA loss in the ASD. To our knowledge, this is the first study to use TBSS to examine WM in individuals with ASD. Our findings indicate that the frontal lobe exhibits abnormal WM microstructure as well as an aberrant neurodevelopment during adolescence in ASD, which support the frontal disconnectivity theory of autism.

Altered White Matter Microstructure in Adolescents With Major Depression: A Preliminary Study

Altered White Matter Microstructure in Adolescents With Major Depression: A Preliminary Study