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Larger putamen in individuals at risk and with manifest bipolar disorder
- Florian Thomas-Odenthal, Frederike Stein, Christoph Vogelbacher, Nina Alexander, Andreas Bechdolf, Felix Bermpohl, Kyra Bröckel, Katharina Brosch, Christoph U. Correll, Ulrika Evermann, Irina Falkenberg, Andreas Fallgatter, Kira Flinkenflügel, Dominik Grotegerd, Tim Hahn, Martin Hautzinger, Andreas Jansen, Georg Juckel, Axel Krug, Martin Lambert, Gregor Leicht, Karolina Leopold, Susanne Meinert, Pavol Mikolas, Christoph Mulert, Igor Nenadić, Julia-Katharina Pfarr, Andreas Reif, Kai Ringwald, Philipp Ritter, Thomas Stamm, Benjamin Straube, Lea Teutenberg, Katharina Thiel, Paula Usemann, Alexandra Winter, Adrian Wroblewski, Udo Dannlowski, Michael Bauer, Andrea Pfennig, Tilo Kircher
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 27 May 2024, pp. 1-11
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Background:
Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.
Methods:In 410 male and female participants aged 17–35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites.
Results:Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake.
Conclusions:Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.
Frontal theta oscillations during emotion regulation in people with borderline personality disorder
- Moritz Haaf, Nenad Polomac, Ana Starcevic, Marvin Lack, Stefanie Kellner, Anna-Lena Dohrmann, Ulrike Fuger, Saskia Steinmann, Jonas Rauh, Guido Nolte, Christoph Mulert, Gregor Leicht
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- Journal:
- BJPsych Open / Volume 10 / Issue 2 / March 2024
- Published online by Cambridge University Press:
- 04 March 2024, e58
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Background
Borderline personality disorder (BPD) is a severe psychiatric disorder conceptualised as a disorder of emotion regulation. Emotion regulation has been linked to a frontolimbic network comprising the dorsolateral prefrontal cortex and the amygdala, which apparently synchronises its activity via oscillatory coupling in the theta frequency range.
AimsTo analyse whether there are distinct differences in theta oscillatory coupling in frontal brain regions between individuals with BPD and matched controls during emotion regulation by cognitive reappraisal.
MethodElectroencephalogram (EEG) recordings were performed in 25 women diagnosed with BPD and 25 matched controls during a cognitive reappraisal task in which participants were instructed to downregulate negative emotions evoked by aversive visual stimuli. Between- and within-group time–frequency analyses were conducted to analyse regulation-associated theta activity (3.5–8.5 Hz).
ResultsOscillatory theta activity differed between the participants with BPD and matched controls during cognitive reappraisal. Regulation-associated theta increases were lower in frontal regions in the BPD cohort compared with matched controls. Functional connectivity analysis for regulation-associated changes in the theta frequency band revealed a lower multivariate interaction measure (MIM) increase in frontal brain regions in persons with BPD compared with matched controls.
ConclusionsOur findings support the notion of alterations in a frontal theta network in BPD, which may be underlying core symptoms of the disorder such as deficits in emotion regulation. The results add to the growing body of evidence for altered oscillatory brain dynamics in psychiatric populations, which might be investigated as individualised treatment targets using non-invasive stimulation methods.
Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features
- Pavol Mikolas, Michael Marxen, Philipp Riedel, Kyra Bröckel, Julia Martini, Fabian Huth, Christina Berndt, Christoph Vogelbacher, Andreas Jansen, Tilo Kircher, Irina Falkenberg, Martin Lambert, Vivien Kraft, Gregor Leicht, Christoph Mulert, Andreas J. Fallgatter, Thomas Ethofer, Anne Rau, Karolina Leopold, Andreas Bechdolf, Andreas Reif, Silke Matura, Felix Bermpohl, Jana Fiebig, Thomas Stamm, Christoph U. Correll, Georg Juckel, Vera Flasbeck, Philipp Ritter, Michael Bauer, Andrea Pfennig
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 22 May 2023, pp. 278-288
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Background
Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features.
MethodsFollowing a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar).
ResultsFor BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11–0.361) and a balanced accuracy of 63.1% (95% CI 55.9–70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI −0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6–67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance.
ConclusionsIndividuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.
Shared and distinct white matter abnormalities in adolescent-onset schizophrenia and adolescent-onset psychotic bipolar disorder
- Johanna Seitz-Holland, Felix L. Nägele, Marek Kubicki, Ofer Pasternak, Kang Ik K. Cho, Morgan Hough, Christoph Mulert, Martha E. Shenton, Timothy J. Crow, Anthony C. D. James, Amanda E. Lyall
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- Journal:
- Psychological Medicine / Volume 53 / Issue 10 / July 2023
- Published online by Cambridge University Press:
- 07 July 2022, pp. 4707-4719
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Background
While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.
MethodsForty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence.
ResultsIndividuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age.
ConclusionsWe observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.