Bipolar II disorder is associated with thinning of prefrontal and temporal cortices involved in affect regulation

Elvsåshagen, Torbjørn; Westlye, Lars T.; Bøen, Erlend; Hol, Per Kristian; Andreassen, Ole A.; Boye, Birgitte; Malt, Ulrik Fredrik

doi:10.1111/bdi.12117

Cited by 60 publications

(74 citation statements)

References 83 publications

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“…Also, reduced gray matter volumes of the left precentral gyrus have been detected in individuals at high risk of MDD because of negative cognitive styles (57). Moreover, our findings are in concert with several neuroimaging studies reporting cortical thinning or gray matter volume reductions in the circumscribed brain regions in BD (12,19,22,23,31,58) and MDD patients (20,57).…”

Section: Discussionsupporting

confidence: 87%

“…Cortical surface area and thickness are also genetically and phenotypically independent (18), but the contribution of cortical thickness toward structural brain abnormalities in mood disorders remains largely unknown. A small number of studies have, however, reported cortical thickness abnormalities in MDD and BD patients in the frontal lobe (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and superior temporal gyrus (22,23,29,31). Moreover, thickness reductions in the inferior and middle temporal (31), parahippocampal (22), and fusiform gyrus (21,23) have been found in BD.…”

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confidence: 99%

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Cortical Thickness in Individuals at High Familial Risk of Mood Disorders as They Develop Major Depressive Disorder

Papmeyer

Giles

Sussmann

et al. 2015

Biological Psychiatry

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Section: Discussionsupporting

confidence: 87%

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confidence: 99%

Cortical Thickness in Individuals at High Familial Risk of Mood Disorders as They Develop Major Depressive Disorder

Papmeyer

Giles

Sussmann

et al. 2015

Biological Psychiatry

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“…However, patients with BDII had smaller cluster sizes mainly in the frontal and temporal regions, indicating that abnormalities in patients with BDII are less widespread and more focal than those in patients with BDI. Our results are in agreement with those of Elvsåshagen and colleagues, 16 who reported thinner cortices in patients with BDII than in controls in bilateral prefrontal and left temporal regions. In their study, however, no differences in surface area were found, and a cluster of abnormally low cortical thickness in the right medial prefrontal regions of patients with BDII was observed -a result that was not found in our study.…”

Section: Patients With Bdi Versus Bdiisupporting

confidence: 94%

“…13 In a study by Elvsåshagen and colleagues, 16 which investigated only cortical thickness and surface area, patients with BDII (n = 36) had thinner cortices than controls (n = 42) in the prefrontal and left temporal regions. Another study found that whereas grey matter deficits in the ventromedial prefrontal and superior frontal regions were found in both subtypes, patients with BDI demonstrated additional bilateral abnormalities in frontal, temporal, parietal and parahippocampal regions.…”

Section: Introductionmentioning

confidence: 99%

Cortical thickness, volume and surface area in patients with bipolar disorder types I and II

Abé

Ekman

Sellgren

et al. 2016

jpn

105

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IntroductionBipolar disorder (BD) is a common chronic psychiatric disorder characterized by mood disturbances with recurrent episodes of mania, hypomania and depression interspersed by euthymic periods. The disorder is not only associated with premature death, significant disability and impaired psychosocial functioning, 1 but also with cognitive impairments. 2Summarizing previous imaging studies of patients with BD, recent meta-analyses and review articles have concluded that these patients demonstrate abnormalities primarily in frontal lobe regions, such as abnormally low volumes not only in the anterior cingulate cortex (ACC), medial and inferior frontal, orbitofrontal, ventral and dorsolateral prefrontal cortices, but also in the temporal and insular cortices. 3-9There are 2 established subtypes of BD: type I and type II. The subtype BDII is distinguished from BDI mainly by the absence of full-blown manic episodes. This and the generally observed lower functional impairment in patients with BDII compared with BDI 10 has led some to describe BDII as a milder form of BDI. But this conclusion is not necessarily accurate, as BDII is characterized by shorter euthymic intervals, more depressive episodes, longer time spent in a state of depression, more comorbidities and greater perceived suffering than BDI. 11,12 The fact that patients with BDI and BDII manifest different symptoms and severity suggests partly different neurobiological mechanisms and pathophysiology. Despite this, most previous studies have focused on patients with BDI or on patients with BDI and BDII combined indiscriminately. The few and small studies that have investigated patients with BDI, BDII and healthy controls suggest that the subtypes are characterized by common neurobiological alterations that are less pronounced in patients with BDII.13-15 One study reported fewer case-control differences in grey matter Background: Bipolar disorder (BD) is a common chronic psychiatric disorder mainly characterized by episodes of mania, hypomania and depression. The disorder is associated with cognitive impairments and structural brain abnormalities, such as lower cortical volumes in primarily frontal brain regions than healthy controls. Although bipolar disorder types I (BDI) and II (BDII) exhibit different symptoms and severity, previous studies have focused on BDI. Furthermore, the most frequently investigated measure in this population is cortical volume. The aim of our study was to investigate abnormalities in patients with BDI and BDII by simultaneously analyzing cortical volume, thickness and surface area, which yields more information about disease-and symptom-related neurobiology. Methods: We used MRI to measure cortical volume, thickness and area in patients with BDI and BDII as well as in healthy controls. The large study cohort enabled us to adjust for important confounding factors. Results: We included 81 patients with BDI, 59 with BDII and 85 controls in our analyses. Cortical volume, thickness and surface area abnormalities were present ...

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“…Similarly, reductions in thickness of the right rACC (Oertel-Knochel et al, 2015), the right dorsomedial PFC, including BA32 (Elvsashagen et al, 2013), and the left rACC (Foland-Ross et al, 2011; Lyoo et al, 2006) have been reported in patients with bipolar disorder.…”

Section: Discussionmentioning

confidence: 64%

Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder

Meier

Drevets

Wurfel

et al. 2016

Brain, Behavior, and Immunity

141

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Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites. Here, using partial posterior predictive distribution mediation analysis, we tested whether the serum concentrations of kynurenine pathway metabolites mediated reductions in cortical thickness in mPFC regions in MDD. Further, we tested whether any association between C-reactive protein (CRP) and cortical thickness would be mediated by kynurenine pathway metabolites. Seventy-three unmedicated subjects who met DSM-IV-TR criteria for MDD and 91 healthy controls (HC) completed MRI scanning using a pulse sequence optimized for tissue contrast resolution. Automated cortical parcellation was performed using the PALS-B12 Brodmann area atlas as implemented in FreeSurfer in order to compare the cortical thickness and cortical area of six PFC regions: Brodmann areas (BA) 9, 10, 11, 24, 25, and 32. Serum concentrations of kynurenine pathway metabolites were determined by high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) detection, while high-sensitivity CRP concentration was measured immunoturbidimetrically. Compared with HCs, the MDD group showed a reduction in cortical thickness of the right BA24 (p<0.01) and BA32 (p<0.05) regions and MDD patients with a greater number of depressive episodes displayed thinner cortex in BA32 (p<0.05). Consistent with our previous findings in an overlapping sample, the KynA/3HK ratio and the log KynA/QA were reduced in the MDD group relative to the HC group (p’s<0.05) and symptoms of anhedonia were negatively correlated with log KynA/QA in the MDD group (p<0.05). Both KynA/3HK and log KynA/QA at least partially mediated the relationship between diagnosis and cortical thickness of right BA32 (p’s<0.05). CRP was inversely associated with BA32 thickness (p<0.01) and KynA/3HK partially mediated the relationship between CRP and the thickness of right BA32 (p<0.05). The results raise the possibility that the relative imbalance between KynA and neurotoxic kynurenine metabolites may partially explain the reductions in mPFC thickness observed in MDD, and further that these changes are more strongly linked to the putative effects of neuroactive kynurenine metabolites than those of inflammatory mediators.

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Bipolar II disorder is associated with thinning of prefrontal and temporal cortices involved in affect regulation

Cited by 60 publications

References 83 publications

Cortical Thickness in Individuals at High Familial Risk of Mood Disorders as They Develop Major Depressive Disorder

Cortical Thickness in Individuals at High Familial Risk of Mood Disorders as They Develop Major Depressive Disorder

Cortical thickness, volume and surface area in patients with bipolar disorder types I and II

Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder

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