White matter hyperintensities in young individuals with bipolar disorder or at high genetic risk

Wadhwa, R. S.; Wang, Wen; Frankland, Andrew; Leung, Vivian; Sinbandhit, Carina; Stuart, Angela; Dawes, Laughlin; Hadži-Pavlović, Dušan; Lévy, Florence; Lenrootl, Rhoshel; Mitchell, Philip B.; Roberts, Gloria

doi:10.1016/j.jad.2018.10.368

Cited by 18 publications

(15 citation statements)

References 48 publications

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“…So far, there is little consensus regarding the best method to determine the presence and severity of WMH. The majority of studies on the occurrence of WMH in children, adolescents and young adults with BD (Table 1) have used (modified) versions of either Fazekas' visual rating scale 26,27,29,30 or Coffey's visual rating scale, 24,28,31 which is based on Fazekas. However, since the Fazekas scale 37 was originally designed to rate the presence and severity of WMH in geriatric samples with Alzheimer's disease and WMHs are known to be much more prevalent and severe among aging individuals, 2 it is not well suited to young populations with limited variability in WMH severity/extent.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Three others reported statistically equivalent WMH rates between BD and HCs, [27][28][29] and one recent study found elevated DWMH but not PVH rates for young adults with BD. 26 Furthermore, it should be noted that due to small sample sizes and/or poor age-and sex-matching of HCs, the results of these prior studies should be interpreted with caution. Nevertheless, a meta-analysis of four of these studies 24,25,27,28 yielded an OR of 5.7 (95%CI 2.3-13.7) for children or adolescents with BD (n=99) vs. HCs (n=124), exceeding the OR of 2.2 in studies on adults only.…”

Section: Introductionmentioning

confidence: 97%

“…Studies on WMHs in children and adolescents or young adults with BD are summarized in Table 1. [24][25][26][27][28][29] The results of studies on WMHs in pediatric BD are highly conflicting: two studies reported that the WMH prevalence was significantly higher among patients with BD than HCs. 24,25 Three others reported statistically equivalent WMH rates between BD and HCs, [27][28][29] and one recent study found elevated DWMH but not PVH rates for young adults with BD.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder

Mehrhof

Popel

Mio

et al. 2021

Braz. J. Psychiatry

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Objective: The increased prevalence rate of white matter hyperintensities is one of the most consistently reported brain abnormalities in adults with bipolar disorder. However, findings in children and adolescents with bipolar disorder are less consistent. Prior studies have been constrained by small sample sizes and/or poor age-and sex-matching of healthy controls. We examined this topic in the largest sample of adolescents with bipolar disorder to date. Methods: T 2-weighted 3-Tesla magnetic resonance imaging data were acquired for 83 adolescents with bipolar disorder diagnosed via the Kiddie Schedule for Affective Disorders and the Schizophrenia, Present and Lifetime version semi-structured interview and 64 age-and sex-matched healthy controls. All acquired scans were examined by neuroradiologists and the presence or absence of white matter hyperintensities was determined for each participant. Results: The prevalence of white matter hyperintensities did not differ between adolescents with bipolar disorder (13.3%) and controls (21.9%; w 2 = 1.90; p = 0.168). Conclusion: In contrast to the study hypothesis, the prevalence of white matter hyperintensities was not higher in adolescents with bipolar disorder than controls. The large sample size and good matching for age and sex bolster the reliability of this negative finding. Future studies are warranted to evaluate the prevalence, incidence, and predictors of white matter hyperintensities in early-onset bipolar disorder prospectively.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder

Mehrhof

Popel

Mio

et al. 2021

Braz. J. Psychiatry

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“…These patterns of alterations are usually accompanied by a reduced diffusivity along the main WM fiber axis, or axial diffusivity (AD), and a lower coherent directionality, measured by fractional anisotropy (FA). WM alterations also concern a volumetric reduction, as described in voxel-based morphometry studies (42), and increased WM hyperintensities (43,44). These WM modifications have been linked to possible alterations in oligodendrocytes, the axons' myelinating cells in the CNS (45).…”

Section: Brain Structural Alterationsmentioning

confidence: 99%

Neuroinflammation in Bipolar Depression

et al. 2020

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Bipolar disorder (BD) is a leading cause of worldwide disability among mood disorders. Pathological mechanisms are still vastly unclear, and current treatments with conventional medications are often unsatisfactory in maintaining symptoms control and an adequate quality of life. Consequently, current research is focusing on shedding new light on disease pathogenesis, to improve therapeutic effectiveness. Recent evidence has suggested a prominent role of inflammation in mood disorders. Elevated levels of peripheral proinflammatory mediators have been reported in BD, as well as in other mood disorders, and people with systemic autoimmune diseases have an increased risk of developing BD. These immunological alterations are stable, and current medications are unable to alter peripheral concentrations even when clinical improvement is evident. These findings have also been replicated in the central nervous system (CNS) milieu, whereas genetic studies have shown that these immune alterations are not due to the disorder itself, being detectable before the illness onset. Moreover, these inflammatory modifications seem to be affected by and linked to other biomarkers of the disorder, such as alterations of white matter (WM) microstructure, metabolism, kynurenine pathway, and circadian rhythmicity. Finally, these immune variations seem to be useful as predictors of therapeutic responsiveness to medications, and in discriminating between clinically different outcomes. The objective of this review is to summarize available evidence on the connection between inflammation and BD, focusing on peripheral inflammatory markers and recent findings on their connection with other typical features of BD, to outline a general overview of the disorder. Moreover, it is meant to analyze the issues with data gathering and interpretation, given the partially contradictory and inconsistent nature of results.

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“…The vast majority of these findings are small but detectable pathologies, typically white matter hyperintensities, that are frequently dismissed as 'not clinically relevant'. This is despite the fact that exactly these changes have been found to predict mental health problems, poor outcome for mental health problems (Firth et al, 2019;Grangeon et al, 2010;Kieseppä et al, 2014;Wadhwa et al, 2019) and poor cognition (Moura et al, 2019) in otherwise neurologically unaffected adults across the lifespan.…”

Section: Current Diagnostic Technology Defines the Limits Of The Funcmentioning

confidence: 98%

What is the Functional / Organic Distinction Actually Doing in Psychiatry and Neurology?

Bell¹,

Wilkinson²,

Greco³

et al. 2020

Preprint

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The functional-organic distinction aims to distinguish symptoms, signs, and syndromes that can be explained by diagnosable biological changes, from those that cannot. The distinction is central to clinical practice and is a key organising principle in diagnostic systems. Following a pragmatist approach that examines meaning through use, we examine how the functional-organic distinction is deployed and conceptualised in psychiatry and neurology. We note that the conceptual scope of the terms 'functional' and 'organic' varies considerably by context. Techniques for differentially diagnosing 'functional' and 'organic' diverge in the strength of evidence they produce as a necessary function of the syndrome in question. Clinicians do not agree on the meaning of the terms and report using them strategically. The distinction often relies on an implied model of 'zero sum' causality and encourages classification of syndromes into discrete ‘functional’ and ‘organic’ versions. Although this clearly applies in some instances, this is often in contrast to our best scientific understanding of neuropsychiatric disorders as arising from a dynamic interaction between personal, social and neuropathological factors. We also note 'functional' and 'organic' have loaded social meanings, creating the potential for social disempowerment and epistemic injustice. Given this, we argue for a better understanding of how strategic simplification and complex scientific reality limit each other. We also note that the contribution of people who experience the interaction between 'functional' and 'organic' factors has rarely informed the validity of this distinction and the dilemmas arising from it, and we highlight this as a research priority.

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White matter hyperintensities in young individuals with bipolar disorder or at high genetic risk

Cited by 18 publications

References 48 publications

Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder

Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder

Neuroinflammation in Bipolar Depression

What is the Functional / Organic Distinction Actually Doing in Psychiatry and Neurology?

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