White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

Peters, Bart D.; Szeszko, Philip R.; Raduà, Joaquim; Ikuta, Toshikazu; Gruner, Patricia; DeRosse, Pamela; Zhang, Jian-Ping; Giorgio, Antonio; Qiu, Deqiang; Tapert, Susan F.; Bräuer, Jens; Asato, Miya R.; Khong, Pek‐Lan; James, Anthony; Gallego, Juan A.; Malhotra, Anil K.

doi:10.1093/schbul/sbs054

Cited by 194 publications

(167 citation statements)

References 39 publications

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“…Taken together, genetic vulnerability for schizophrenia may result in frontostriatal neurodevelopmental changes already before adolescence and this may evolve into decreased mean FA during adulthood. In contrast to decreasing FA measures in schizophrenia offspring, our finding of an increase in mean FA in the tracts connecting the nucleus accumbens and DLPFC with progressing age in typical developing control adolescents is consistent with previous DTI studies (Giorgio et al, 2008;Lebel et al, 2008;Peper et al, 2013;Peters et al, 2012). As FA may be used as an index for the microstructural directionality of white matter fiber bundles (Basser and Pierpaoli, 1996), our finding of increasing FA across age in control adolescents may reflect maturation of white matter tracts across adolescence.…”

Section: Discussionsupporting

confidence: 90%

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Leeuw

Bohlken

Mandl

et al. 2016

Neuropsychopharmacol

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Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

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Section: Discussionsupporting

confidence: 90%

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Leeuw

Bohlken

Mandl

et al. 2016

Neuropsychopharmacol

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“…Such a finding lends evidence to support the hypothesis that those with ADHD may engage in adaptive processing strategies to compensate for impairments in other brain regions. 64 Furthermore, our results are in line with those of studies in healthy participants that demonstrate the importance of the SLF, especially the right side, in attention performance 29 and working memory, 30 which are considered to be major neuropsychological deficits in individuals with ADHD. 65 In addition, our findings raised a noteworthy issue: most studies reported correlations between the frontostriatal tracts and ADHD symptoms without considering the effects of other related white matter tracts.…”

Section: Correlations Between the Slf And Adhd Symptoms And Attentionsupporting

confidence: 91%

“…27 The superior parietal lobule participates in the transmission of spatial information for body parts, the caudal part of the inferior parietal lobule is responsible for visual attention, and the inferior parietal lobule plays a role in working memory. 28 The superior longitudinal fasciculus (SLF) as well as the interconnecting frontal, parietal and temporal cortices are involved in attention performance 29 and working memory 30 in control children. Alteration in the SLF has been demonstrated in children [31][32][33] and adults 34,35 with ADHD.…”

Section: J Psychiatry Neurosci 2015;40(5)mentioning

confidence: 99%

Altered white matter tract property related to impaired focused attention, sustained attention, cognitive impulsivity and vigilance in attention-deficit/hyperactivity disorder

Chiang

Chen

et al. 2015

jpn

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Background:The neural substrate for clinical symptoms and neuropsychological performance in individuals with attention-deficit/ hyperactivity disorder (ADHD) has rarely been studied and has yielded inconsistent results. We sought to compare the microstructural property of fibre tracts associated with the prefrontal cortex and its association with ADHD symptoms and a wide range of attention performance in youth with ADHD and healthy controls. Methods: We assessed youths with ADHD and age-, sex-, handedness-, coil-and intelligence-matched controls using the Conners' Continuous Performance Test (CCPT) for attention performance and MRI. The 10 target tracts, including the bilateral frontostriatal tracts (caudate to dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus (SLF) and cingulum bundle were reconstructed using diffusion spectrum imaging tractography. We computed generalized fractional anisotropy (GFA) values to indicate tract-specific microstructural property. Results: We included 50 youths with ADHD and 50 healthy controls in our study. Youths with ADHD had lower GFA in the left frontostriatal tracts, bilateral SLF and right cingulum bundle and performed worse in the CCPT than controls. Furthermore, alteration of the right SLF GFA was most significantly associated with the clinical symptom of inattention in youths with ADHD. Finally, youths with ADHD had differential association patterns of the 10 fibre tract GFA values with attention performance compared with controls. Limitations: Ten of the youths with ADHD were treated with methylphenidate, which may have long-term effects on microstructural property. Conclusion: Our study highlights the importance of the SLF, cingulum bundle and frontostriatal tracts for clinical symptoms and attention performance in youths with ADHD and demonstrates the involvement of different fibre tracts in attention performance in these individuals.Chiang et al. 326 J Psychiatry Neurosci 2015;40(5)4-repeat allele at DRD4. 11 On the other hand, more commission errors were reported for those with the G1287A genotype of the norepinephrine transporter gene.12 Therefore, the CPT may provide information more closely related to the underlying neuropathology of ADHD than the clinical symptoms do.Increasingly, studies have adopted imaging techniques to explore the neuropathology of ADHD. Structural and functional neuroimaging findings have highlighted that prefront al cortex abnormality may contribute to dysfunction in attention regulation, resulting in the behavioural manifestation of ADHD. 13 Among the subdivisions of the prefrontal cortex, the dorsolateral prefrontal cortex (DLPFC) plays a specific role in attention and executive functions, 14 the ventrolateral prefrontal cortex (VLPFC) in behavioural inhibition, 15,16 the orbitofrontal cortex (OFC) in motivation and reward, and the anterior cingulate cortex (ACC) in reward-based decision making. 17 Volumetric and functional MRI studies have also consistently reported...

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“…We suggest several possible reasons for the reported discrepancies: (1) in OCD, white matter alterations might be subtle thus difficult to detect; (2) medication effects seem to confound the findings (Yoo et al, 2007;Fan et al, 2012;Benedetti et al, 2013;Radua et al, 2014); (3) results are highly variable across pediatric, adolescent and adult patients due to changes in white matter architecture throughout brain development (Peters et al, 2012); (4) debate has risen recently on whether FA alone is sufficient and sufficiently representative to indicate changes in white matter microstructure (Hasan, 2006;Fan et al, 2012;Szczepankiewicz et al, 2014); and (5) small samples and inconsistent methodologies have been used (Radua et al, 2014).…”

Section: Introductionmentioning

confidence: 93%

Mild White Matter Changes in Un-Medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings

Fan

Heuvel

Cath

et al. 2017

European Neuropsychopharmacology

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Objective: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with moderate genetic influences and white matter abnormalities in frontal-striatal and limbic regions. Inconsistencies in reported white matter results from diffusion tensor imaging (DTI) studies can be explained, at least partly, by medication use and between-group differences in disease profile and stage. We used a family design aiming to establish whether white matter abnormalities, if present in un-medicated OCD patients, also exist in their unaffected siblings.Method: Forty-four OCD patients, un-medicated for at least the past 4 weeks, 15 of their unaffected siblings, and 37 healthy controls (HC) underwent DTI using a 3-Tesla MRI-scanner. Data analysis was done using tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values were compared within seven skeletonised regions of interest (ROIs), i.e., corpus callosum, bilateral cingulum bundle, bilateral inferior longitudinal fasciculus/ frontal-occipital fasciculus (ILF/FOF) and bilateral superior longitudinal fasciculus (SLF).Results: Un-medicated OCD patients, compared with HC, had significantly lower FA in the left cingulum bundle. FA was trend-significantly lower in all other ROIs, except for the corpus callosum. Significant three-group differences in FA (and in RD at trend-significant level) were observed in the left cingulum bundle, with the unaffected siblings representing an intermediate group between OCD patients and HC.Conclusions: OCD patients showed lower FA in the left cingulum bundle, partly driven by trend-significantly higher values in RD. Since the unaffected siblings were found to be an intermediate group between OCD patients and HC, this white matter alteration may be considered an endophenotype for OCD.

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White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

Cited by 194 publications

References 39 publications

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Altered white matter tract property related to impaired focused attention, sustained attention, cognitive impulsivity and vigilance in attention-deficit/hyperactivity disorder

Mild White Matter Changes in Un-Medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings

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