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White matter correlates of adolescent depression: structural evidence for frontolimbic disconnectivity.

ABSTRACT: Despite the significant prevalence of adolescent depression, little is known about the neuroanatomical basis of this disorder. Functional dysregulation in frontolimbic circuitry has been suggested as a key neural correlate of adult and adolescent depression impeding emotional regulation. However, less is known about whether this dysregulation is overlaid on impaired white matter microstructure. Guided by neuroimaging findings, we test the a priori hypotheses that adolescent depression is associated with alterations in white matter microstructure in the uncinate fasciculus (UF) and cingulum bundles.Diffusion tensor magnetic resonance imaging (DTI) data were obtained on 52 unmedicated adolescents with major depressive disorder (MDD) and 42 matched controls. We calculated fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) for bilateral UF and cingulum. We also completed a voxelwise comparison of participants with depression and control participants using tract-based spatial statistics (TBSS).Adolescents with depression had significantly lower FA and higher RD in bilateral UF; no significant differences were observed in cingulum. TBSS results additionally revealed lower FA values in the white matter associated with the limbic-cortical-striatal-thalamic circuit, corpus callosum, and anterior and superior corona radiata.Unmedicated adolescent depression is associated with reduced fractional anisotropy in emotion regulatory networks, which may underlie the functional differences in frontolimbic circuitry characterizing depressive disorder. Given the relatively recent onset of depression in our sample, our findings in the context of the current literature provide preliminary evidence that reduced fractional anisotropy in the UF could be a predisposing risk factor for depression.

SUBMITTER: LeWinn KZ

PROVIDER: S-EPMC4112055 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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White matter correlates of adolescent depression: structural evidence for frontolimbic disconnectivity.

LeWinn Kaja Z KZ Connolly Colm G CG Wu Jing J Drahos Miroslav M Hoeft Fumiko F Ho Tiffany C TC Simmons Alan N AN Yang Tony T TT

Journal of the American Academy of Child and Adolescent Psychiatry 20140604 8

<h4>Objective</h4>Despite the significant prevalence of adolescent depression, little is known about the neuroanatomical basis of this disorder. Functional dysregulation in frontolimbic circuitry has been suggested as a key neural correlate of adult and adolescent depression impeding emotional regulation. However, less is known about whether this dysregulation is overlaid on impaired white matter microstructure. Guided by neuroimaging findings, we test the a priori hypotheses that adolescent dep ...[more]

PMID: 25062597

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Project description:Background and purposeImpairment of cognitive functions occurs in essential tremor, though the mechanism is largely unknown. The aim of this study was to find microstructural correlates of cognitive dysfunction seen in essential tremor by using DTI and neuropsychological assessment.Materials and methodsFifty-five patients with essential tremor and 55 matched healthy controls were evaluated. Essential tremor was diagnosed by using the National Institutes of Health criteria. Subjects were assessed by using a structured neuropsychological battery. DTI data were acquired by using 3T MR imaging and were analyzed by using tract-based spatial statistics. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were analyzed.ResultsPatients were considered cognitively impaired when the test score was 1.5 SDs below or above the mean of healthy controls (depending on the type of test) in ≥3 neuropsychological tests. Patients with cognitive impairment had significantly higher mean diffusivity, radial diffusivity, and axial diffusivity values in the bilateral frontoparietal regions. In patients with cognitive impairment, mean diffusivity, radial diffusivity, and axial diffusivity showed correlations with various neuropsychological test scores. Executive function correlated with DTI measures of the frontal white matter, cingulum, inferior superior longitudinal and uncinate fasciculi, anterior thalamic radiations, and posterior lobe of the cerebellum. Visuospatial function correlated with the right parieto-occipital lobe, whereas visual-verbal memories correlated with the anterior thalamic radiations, inferior longitudinal and uncinate fasciculi, and the posterior lobe of the cerebellum. No significant correlations were found between fractional anisotropy and any of the neuropsychological test scores.ConclusionsThe present study demonstrates a correlation between neuropsychological test scores and DTI measures, suggesting a neuroanatomic basis for cognitive impairment seen in patients with essential tremor.

Project description:IntroductionCure rates for pediatric acute lymphoblastic leukemia (ALL) have reached an all-time high (>90%); however, neurocognitive difficulties continue to affect quality of life in at least a subset of survivors. There are relatively few quantitative neuroimaging studies in child and adolescent ALL survivors treated with chemotherapy only. Use of different outcome measures or limited sample sizes restrict our ability to make inferences about patterns of brain development following chemotherapy treatment. In this study, we used magnetic resonance imaging (MRI) to evaluate brain outcomes in ALL survivors, comparing against a group of typically developing, cancer free peers.Materials and methodsParticipants included 71 ALL survivors, on average 8 years after diagnosis and 8-18 years of age, and 83 typically developing controls. Anatomical MRI was performed to evaluate brain structure; diffusion and magnetization transfer MRI were used to examine brain tissue microstructure.ResultsSuccessful MRI scans were acquired in 67 survivors (94%) and 82 controls (99%). Structurally, ALL survivors exhibited widespread reductions in brain volume, with 6% less white matter and 5% less gray matter than controls (p = 0.003 and 0.0006 respectively). Much of the brain appeared affected - 71 of 90 evaluated structures showed smaller volume - with the most notable exception being the occipital lobe, where no significant differences were observed. Average full-scale IQ in the survivor and control groups were 95 (CI 92-99) and 110 (CI 107-113), respectively. Using data from the NIH Pediatric MRI Data Repository, we evaluated the extent to which elevated IQ in the control group might affect the structural differences observed. We estimated that two thirds of the observed brain differences were attributable to ALL and its treatment. In addition to the structural changes, survivors showed, on average, globally lower white matter fractional anisotropy (-3%) and higher radial diffusivity (+5%) (p < 10-6), but no differences in magnetization transfer ratio.ConclusionsNeuroanatomical alterations in late childhood and adolescent ALL survivors treated with chemotherapy-only protocols are widespread, with white matter being somewhat more affected than gray matter. These MRI results indicate brain development is altered in ALL survivors and highlight the need to examine how these alterations emerge.

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White matter correlates of adolescent depression: structural evidence for frontolimbic disconnectivity.

Publications

White matter correlates of adolescent depression: structural evidence for frontolimbic disconnectivity.

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