Publications by authors named "Hannah Lemke"

19 Publications

  • Page 1 of 1

Neural processing of emotional facial stimuli in specific phobia: An fMRI study.

Depress Anxiety 2021 Jul 5. Epub 2021 Jul 5.

Institute for Translational Psychiatry, University of Münster, Münster, Germany.

Background: Patients with specific phobia (SP) show altered brain activation when confronted with phobia-specific stimuli. It is unclear whether this pathogenic activation pattern generalizes to other emotional stimuli. This study addresses this question by employing a well-powered sample while implementing an established paradigm using nonspecific aversive facial stimuli.

Methods: N = 111 patients with SP, spider subtype, and N = 111 healthy controls (HCs) performed a supraliminal emotional face-matching paradigm contrasting aversive faces versus shapes in a 3-T magnetic resonance imaging scanner. We performed region of interest (ROI) analyses for the amygdala, the insula, and the anterior cingulate cortex using univariate as well as machine-learning-based multivariate statistics based on this data. Additionally, we investigated functional connectivity by means of psychophysiological interaction (PPI).

Results: Although the presentation of emotional faces showed significant activation in all three ROIs across both groups, no group differences emerged in all ROIs. Across both groups and in the HC > SP contrast, PPI analyses showed significant task-related connectivity of brain areas typically linked to higher-order emotion processing with the amygdala. The machine learning approach based on whole-brain activity patterns could significantly differentiate the groups with 73% balanced accuracy.

Conclusions: Patients suffering from SP are characterized by differences in the connectivity of the amygdala and areas typically linked to emotional processing in response to aversive facial stimuli (inferior parietal cortex, fusiform gyrus, middle cingulate, postcentral cortex, and insula). This might implicate a subtle difference in the processing of nonspecific emotional stimuli and warrants more research furthering our understanding of neurofunctional alteration in patients with SP.
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http://dx.doi.org/10.1002/da.23191DOI Listing
July 2021

Interaction of developmental factors and ordinary stressful life events on brain structure in adults.

Neuroimage Clin 2021 21;30:102683. Epub 2021 Apr 21.

Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, Hans-Meerwein-Str. 6, 35032 Marburg, Germany; Marburg University Hospital - UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated. Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain. SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume. The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.
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http://dx.doi.org/10.1016/j.nicl.2021.102683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102615PMC
April 2021

Interaction of developmental factors and ordinary stressful life events on brain structure in adults.

Neuroimage Clin 2021 21;30:102683. Epub 2021 Apr 21.

Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, Hans-Meerwein-Str. 6, 35032 Marburg, Germany; Marburg University Hospital - UKGM, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated. Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain. SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume. The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.
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http://dx.doi.org/10.1016/j.nicl.2021.102683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102615PMC
April 2021

Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning.

Neuropsychopharmacology 2021 Jun 14. Epub 2021 Jun 14.

Max Planck Institute of Psychiatry, Munich, Germany.

Psychiatric disorders show heterogeneous symptoms and trajectories, with current nosology not accurately reflecting their molecular etiology and the variability and symptomatic overlap within and between diagnostic classes. This heterogeneity impedes timely and targeted treatment. Our study aimed to identify psychiatric patient clusters that share clinical and genetic features and may profit from similar therapies. We used high-dimensional data clustering on deep clinical data to identify transdiagnostic groups in a discovery sample (N = 1250) of healthy controls and patients diagnosed with depression, bipolar disorder, schizophrenia, schizoaffective disorder, and other psychiatric disorders. We observed five diagnostically mixed clusters and ordered them based on severity. The least impaired cluster 0, containing most healthy controls, showed general well-being. Clusters 1-3 differed predominantly regarding levels of maltreatment, depression, daily functioning, and parental bonding. Cluster 4 contained most patients diagnosed with psychotic disorders and exhibited the highest severity in many dimensions, including medication load. Depressed patients were present in all clusters, indicating that we captured different disease stages or subtypes. We replicated all but the smallest cluster 1 in an independent sample (N = 622). Next, we analyzed genetic differences between clusters using polygenic scores (PGS) and the psychiatric family history. These genetic variables differed mainly between clusters 0 and 4 (prediction area under the receiver operating characteristic curve (AUC) = 81%; significant PGS: cross-disorder psychiatric risk, schizophrenia, and educational attainment). Our results confirm that psychiatric disorders consist of heterogeneous subtypes sharing molecular factors and symptoms. The identification of transdiagnostic clusters advances our understanding of the heterogeneity of psychiatric disorders and may support the development of personalized treatments.
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http://dx.doi.org/10.1038/s41386-021-01051-0DOI Listing
June 2021

The course of disease in major depressive disorder is associated with altered activity of the limbic system during negative emotion processing.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jun 5. Epub 2021 Jun 5.

Institute for Translational Psychiatry, University of Münster, Münster, Germany. Electronic address:

Background: Brain functional alterations during emotion processing in patients with major depressive disorder (MDD) compared to healthy controls (HC) are frequently reported. However, evidence for functional correlates of emotion processing with regard to MDD trajectories is scarce. The present study investigated the role of lifetime disease course for limbic brain activation during negative emotional face processing in patients with MDD.

Methods: In a large sample of MDD patients (n=333; 58.55% female) and HC (n=333; 60.06% female), brain activation was investigated during a negative emotional face processing task within a cross-sectional design. Group differences between HC and MDD were analysed. Previous disease course, characterized by two components, namely Hospitalization and Duration of Illness, was regressed on brain activation of the amygdala, (para-)hippocampus and insula in MDD patients.

Results: MDD patients showed increased activation in the amygdala, insula and hippocampus compared to HC (all p<.045). The Hospitalization component showed negative associations with brain activation in the bilateral insula (right: p=.026, left: p=.019) and (para-)hippocampus (right: p=.038, left: p=.031). No significant associations were found for the Duration of Illness component (all p>.057).

Conclusions: This study investigated negative emotion processing in a large sample of MDD patients and HC. Our results confirm limbic hyperactivation in patients with MDD during negative emotion processing, however this hyperactivation may resolve with a more severe lifetime disease course in the insula and (para-)hippocampus - brain regions involved in emotion processing and regulation. These findings need further replication in longitudinal studies.
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http://dx.doi.org/10.1016/j.bpsc.2021.05.008DOI Listing
June 2021

Social support and hippocampal volume are negatively associated in adults with previous experience of childhood maltreatment.

J Psychiatry Neurosci 2021 Apr 27;46(3):E328-E336. Epub 2021 Apr 27.

From the Department of Psychiatry, University of Münster, Münster, Germany (Förster, Danzer, Redlich, Opel, Grotegerd, Leehr, Dohm, Enneking, Meinert, Goltermann, Lemke, Waltemate, Thiel, Behnert, Hahn, Repple, Dannlowski); the Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, TU Dresden, Dresden, Germany (Förster); the Department of Clinical Psychology, University of Halle, Halle, Germany (Redlich); the Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany (Brosch, Stein, Meller, Ringwald, Schmitt, Steinsträter, Jansen, Krug, Nenadic, Kircher); the Core-Unit Brain Imaging, Faculty of Medicine, University of Marburg, Marburg, Germany (Jansen); the Department of Psychiatry, University of Bonn, Bonn, Germany (Krug); and the University Clinic for Clinical Radiology, University of Münster, Münster, Germany (Kugel, Heindel).

Background: Childhood maltreatment has been associated with reduced hippocampal volume in healthy individuals, whereas social support, a protective factor, has been positively associated with hippocampal volumes. In this study, we investigated how social support is associated with hippocampal volume in healthy people with previous experience of childhood maltreatment.

Methods: We separated a sample of 446 healthy participants into 2 groups using the Childhood Trauma Questionnaire: 265 people without maltreatment and 181 people with maltreatment. We measured perceived social support using a short version of the Social Support Questionnaire. We examined hippocampal volume using automated segmentation (Freesurfer). We conducted a social support × group analysis of covariance on hippocampal volumes controlling for age, sex, total intracranial volume, site and verbal intelligence.

Results: Our analysis revealed significantly lower left hippocampal volume in people with maltreatment (left F1,432 = 5.686, p = 0.018; right F1,433 = 3.371, p = 0.07), but no main effect of social support emerged. However, we did find a significant social support × group interaction for left hippocampal volume (left F1,432 = 5.712, p = 0.017; right F1,433 = 3.480, p = 0.06). In people without maltreatment, we observed a trend toward a positive association between social support and hippocampal volume. In contrast, social support was negatively associated with hippocampal volume in people with maltreatment.

Limitations: Because of the correlative nature of our study, we could not infer causal relationships between social support, maltreatment and hippocampal volume.

Conclusion: Our results point to a complex dynamic between environmental risk, protective factors and brain structure - in line with previous evidence - suggesting a detrimental effect of maltreatment on hippocampal development.
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http://dx.doi.org/10.1503/jpn.200162DOI Listing
April 2021

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Mol Psychiatry 2021 Apr 16. Epub 2021 Apr 16.

Unit for Psychosomatics / CL Outpatient Clinic for Adults, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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http://dx.doi.org/10.1038/s41380-021-01098-xDOI Listing
April 2021

Psychopathological Syndromes Across Affective and Psychotic Disorders Correlate With Gray Matter Volumes.

Schizophr Bull 2021 Apr 16. Epub 2021 Apr 16.

Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.

Introduction: More than a century of research on the neurobiological underpinnings of major psychiatric disorders (major depressive disorder [MDD], bipolar disorder [BD], schizophrenia [SZ], and schizoaffective disorder [SZA]) has been unable to identify diagnostic markers. An alternative approach is to study dimensional psychopathological syndromes that cut across categorical diagnoses. The aim of the current study was to identify gray matter volume (GMV) correlates of transdiagnostic symptom dimensions.

Methods: We tested the association of 5 psychopathological factors with GMV using multiple regression models in a sample of N = 1069 patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MDD (n = 818), BD (n = 132), and SZ/SZA (n = 119). T1-weighted brain images were acquired with 3-Tesla magnetic resonance imaging and preprocessed with CAT12. Interactions analyses (diagnosis × psychopathological factor) were performed to test whether local GMV associations were driven by DSM-IV diagnosis. We further tested syndrome specific regions of interest (ROIs).

Results: Whole brain analysis showed a significant negative association of the positive formal thought disorder factor with GMV in the right middle frontal gyrus, the paranoid-hallucinatory syndrome in the right fusiform, and the left middle frontal gyri. ROI analyses further showed additional negative associations, including the negative syndrome with bilateral frontal opercula, positive formal thought disorder with the left amygdala-hippocampus complex, and the paranoid-hallucinatory syndrome with the left angular gyrus. None of the GMV associations interacted with DSM-IV diagnosis.

Conclusions: We found associations between psychopathological syndromes and regional GMV independent of diagnosis. Our findings open a new avenue for neurobiological research across disorders, using syndrome-based approaches rather than categorical diagnoses.
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http://dx.doi.org/10.1093/schbul/sbab037DOI Listing
April 2021

DLPFC volume is a neural correlate of resilience in healthy high-risk individuals with both childhood maltreatment and familial risk for depression.

Psychol Med 2021 Apr 16:1-7. Epub 2021 Apr 16.

Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039Marburg, Germany.

Background: Two prominent risk factors for major depressive disorder (MDD) are childhood maltreatment (CM) and familial risk for MDD. Despite having these risk factors, there are individuals who maintain mental health, i.e. are resilient, whereas others develop MDD. It is unclear which brain morphological alterations are associated with this kind of resilience. Interaction analyses of risk and diagnosis status are needed that can account for complex adaptation processes, to identify neural correlates of resilience.

Methods: We analyzed brain structural data (3T magnetic resonance imaging) by means of voxel-based morphometry (CAT12 toolbox), using a 2 × 2 design, comparing four groups (N = 804) that differed in diagnosis (healthy v. MDD) and risk profiles (low-risk, i.e. absence of CM and familial risk v. high-risk, i.e. presence of both CM and familial risk). Using regions of interest (ROIs) from the literature, we conducted an interaction analysis of risk and diagnosis status.

Results: Volume in the left middle frontal gyrus (MFG), part of the dorsolateral prefrontal cortex (DLPFC), was significantly higher in healthy high-risk individuals. There were no significant results for the bilateral superior frontal gyri, frontal poles, pars orbitalis of the inferior frontal gyri, and the right MFG.

Conclusions: The healthy high-risk group had significantly higher volumes in the left DLPFC compared to all other groups. The DLPFC is implicated in cognitive and emotional processes, and higher volume in this area might aid high-risk individuals in adaptive coping in order to maintain mental health. This increased volume might therefore constitute a neural correlate of resilience to MDD in high risk.
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http://dx.doi.org/10.1017/S0033291721001094DOI Listing
April 2021

Association Between Genetic Risk for Type 2 Diabetes and Structural Brain Connectivity in Major Depressive Disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Mar 5. Epub 2021 Mar 5.

Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.

Background: Major depressive disorder (MDD) and type 2 diabetes mellitus (T2D) are known to share clinical comorbidity and to have genetic overlap. Besides their shared genetics, both diseases seem to be associated with alterations in brain structural connectivity and impaired cognitive performance, but little is known about the mechanisms by which genetic risk of T2D might affect brain structure and function and if they do, how these effects could contribute to the disease course of MDD.

Methods: This study explores the association of polygenic risk for T2D with structural brain connectome topology and cognitive performance in 434 nondiabetic patients with MDD and 539 healthy control subjects.

Results: Polygenic risk score for T2D across MDD patients and healthy control subjects was found to be associated with reduced global fractional anisotropy, a marker of white matter microstructure, an effect found to be predominantly present in MDD-related fronto-temporo-parietal connections. A mediation analysis further suggests that this fractional anisotropy variation may mediate the association between polygenic risk score and cognitive performance.

Conclusions: Our findings provide preliminary evidence of a polygenic risk for T2D to be linked to brain structural connectivity and cognition in patients with MDD and healthy control subjects, even in the absence of a direct T2D diagnosis. This suggests an effect of T2D genetic risk on white matter integrity, which may mediate an association of genetic risk for diabetes and cognitive impairments.
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http://dx.doi.org/10.1016/j.bpsc.2021.02.010DOI Listing
March 2021

Apolipoprotein E homozygous ε4 allele status: Effects on cortical structure and white matter integrity in a young to mid-age sample.

Eur Neuropsychopharmacol 2021 May 27;46:93-104. Epub 2021 Feb 27.

Department of Psychiatry, University of Münster, Münster, Germany. Electronic address:

Apolipoprotein E (APOE) genotype is the strongest single gene predictor of Alzheimer's disease (AD) and has been frequently associated with AD-related brain structural alterations before the onset of dementia. While previous research has primarily focused on hippocampal morphometry in relation to APOE, sporadic recent findings have questioned the specificity of the hippocampus and instead suggested more global effects on the brain. With the present study we aimed to investigate associations between homozygous APOE ε4 status and cortical gray matter structure as well as white matter microstructure. In our study, we contrasted n = 31 homozygous APOE ε4 carriers (age=34.47 years, including a subsample of n = 12 subjects with depression) with a demographically matched sample without an ε4 allele (resulting total sample: N = 62). Morphometry analyses included a) Freesurfer based cortical segmentations of thickness and surface area measures and b) tract based spatial statistics of DTI measures. We found pronounced and widespread reductions in cortical surface area of ε4 homozygotes in 57 out of 68 cortical brain regions. In contrast, no differences in cortical thickness were observed. Furthermore, APOE ε4 homozygous carriers showed significantly lower fractional anisotropy in the corpus callosum, the right internal and external capsule, the left corona radiata and the right fornix. The present findings support a global rather than regionally specific effect of homozygous APOE ε4 allele status on cortical surface area and white matter microstructure. Future studies should aim to delineate the clinical implications of these findings.
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http://dx.doi.org/10.1016/j.euroneuro.2021.02.006DOI Listing
May 2021

Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group.

Transl Psychiatry 2020 12 8;10(1):425. Epub 2020 Dec 8.

Department of Psychiatry, University of Münster, Münster, Germany.

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.
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http://dx.doi.org/10.1038/s41398-020-01109-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723989PMC
December 2020

White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder.

Psychol Med 2020 Sep 14:1-9. Epub 2020 Sep 14.

Department of Psychiatry, University of Münster, Münster, Germany.

Background: Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.

Methods: A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.

Results: Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.

Conclusions: Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.
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http://dx.doi.org/10.1017/S0033291720002950DOI Listing
September 2020

Polygenic risk for schizophrenia and schizotypal traits in non-clinical subjects.

Psychol Med 2020 Aug 6:1-11. Epub 2020 Aug 6.

Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, UKGM, Rudolf-Bultmann-Str. 8, 35039Marburg, Germany.

Background: Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.

Methods: We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.

Results: We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.

Conclusions: This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
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http://dx.doi.org/10.1017/S0033291720002822DOI Listing
August 2020

Attachment and social support mediate the association between childhood maltreatment and depressive symptoms.

J Affect Disord 2020 08 11;273:310-317. Epub 2020 May 11.

Department of Clinical Psychology and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany; Department of Clinical Psychology and Psychotherapy, University of Greifswald, Greifswald, Germany.

Objective: To examine attachment insecurity and low social support as potential mediators of the association between childhood maltreatment (CM) types and depression severity in patients with a lifetime history of major depressive disorders (MDD).

Method: Participants with an acute or remitted MDD (N = 580) completed questionnaires about CM (Childhood Trauma Questionnaire), attachment (Relationship Scales Questionnaire), social support (Social Support Questionnaire), and depression severity (Beck Depression Inventory). Mediation and path models with CM types as independent variables, attachment avoidance and anxiety as mediators and depression severity as dependent variable were calculated. In addition, a sequential mediation model with attachment insecurity and social support as mediators of the association between CM and depression was tested.

Results: Attachment avoidance and anxiety partially mediated the effect of CM on depression. In the path model including the different CM types, there were significant indirect effects of emotional abuse on depression via attachment anxiety and of emotional neglect on depression via attachment avoidance. Results also supported the hypothesized sequential mediation via attachment insecurity and social support.

Limitations: A cross-sectional design with a retrospective self-report measure of CM was used and the developmental timing of exposure to CM was not considered.

Conclusion: Our findings suggest that the effect of emotional abuse and emotional neglect on depression is partially mediated by attachment avoidance and anxiety. Further, the results support the hypothesis of a sequential mediation via attachment insecurity and social support. Accordingly, attachment insecurity is discussed as a target of psychotherapy for patients with MDD and CM.
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http://dx.doi.org/10.1016/j.jad.2020.04.041DOI Listing
August 2020

Brain functional effects of electroconvulsive therapy during emotional processing in major depressive disorder.

Brain Stimul 2020 Jul - Aug;13(4):1051-1058. Epub 2020 Apr 7.

Department of Psychiatry, University of Münster, Germany. Electronic address:

Background: In treatment-resistant major depressive disorder (MDD), electroconvulsive therapy (ECT) is a treatment with high efficacy. While knowledge regarding changes in brain structure following ECT is growing, the effects of ECT on brain function during emotional processing are largely unknown.

Objective: We investigated the effects of ECT on the activity of the anterior cingulate cortex (ACC) and amygdala during negative emotional stimuli processing and its association with clinical response.

Methods: In this non-randomized longitudinal study, patients with MDD (n = 37) were assessed before and after treatment with ECT. Healthy controls (n = 37) were matched regarding age and gender. Functional magnetic resonance imaging (fMRI) was obtained twice, at baseline and after six weeks using a supraliminal face-matching paradigm. In order to evaluate effects of clinical response, additional post-hoc analyses were performed comparing responders to non-responders.

Results: After ECT, patients with MDD showed a statistically significant increase in ACC activity during processing of negative emotional stimuli (p = .039). This effect was driven by responders (p = .023), while non-responders showed no increase. Responders also had lower pre-treatment ACC activity compared to non-responders (p = .025). No significant effects in the amygdala could be observed.

Conclusions: ECT leads to brain functional changes in the ACC, a relevant region for emotional regulation during processing of negative stimuli. Furthermore, baseline ACC activity might serve as a biomarker for treatment response. Findings are in accordance with recent studies highlighting properties of pre-treatment ACC to be associated with general antidepressive treatment response.
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http://dx.doi.org/10.1016/j.brs.2020.03.018DOI Listing
December 2020

Severity of current depression and remission status are associated with structural connectome alterations in major depressive disorder.

Mol Psychiatry 2020 07 22;25(7):1550-1558. Epub 2019 Nov 22.

Connectome Lab, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Major depressive disorder (MDD) is associated to affected brain wiring. Little is known whether these changes are stable over time and hence might represent a biological predisposition, or whether these are state markers of current disease severity and recovery after a depressive episode. Human white matter network ("connectome") analysis via network science is a suitable tool to investigate the association between affected brain connectivity and MDD. This study examines structural connectome topology in 464 MDD patients (mean age: 36.6 years) and 432 healthy controls (35.6 years). MDD patients were stratified categorially by current disease status (acute vs. partial remission vs. full remission) based on DSM-IV criteria. Current symptom severity was assessed continuously via the Hamilton Depression Rating Scale (HAMD). Connectome matrices were created via a combination of T1-weighted magnetic resonance imaging (MRI) and tractography methods based on diffusion-weighted imaging. Global tract-based metrics were not found to show significant differences between disease status groups, suggesting conserved global brain connectivity in MDD. In contrast, reduced global fractional anisotropy (FA) was observed specifically in acute depressed patients compared to fully remitted patients and healthy controls. Within the MDD patients, FA in a subnetwork including frontal, temporal, insular, and parietal nodes was negatively associated with HAMD, an effect remaining when correcting for lifetime disease severity. Therefore, our findings provide new evidence of MDD to be associated with structural, yet dynamic, state-dependent connectome alterations, which covary with current disease severity and remission status after a depressive episode.
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http://dx.doi.org/10.1038/s41380-019-0603-1DOI Listing
July 2020

Electrophysiological correlates of performance monitoring under social observation in patients with social anxiety disorder and healthy controls.

Biol Psychol 2018 02 11;132:71-80. Epub 2017 Nov 11.

Institute of Medical Psychology and Systems Neuroscience, University of Münster, Von-Esmarch-Str. 52, 48149 Münster, Germany.

Previous research suggests that electrophysiological correlates of performance monitoring, in particular the error-related negativity (ERN), vary according to psychopathology and context factors. The present study examined the effect of social context on behavioral and electrophysiological correlates of performance monitoring in healthy adult subjects and in patients with social anxiety disorder (SAD). Participants performed two runs of a Go/NoGo flanker task in different social conditions: in the observation condition, they were observed by a confederate while performing the task, whereas there was no observation in the control condition. Behavioral data showed that accuracy and response times were not modulated by social observation and also did not systematically differ between groups. Post-error slowing was more pronounced in patients, independent of observation condition. ERN amplitudes were generally increased under social observation as compared to the control condition regardless of group (patients, controls). No effects of social context or group were found for PE, NoGo-N2, and NoGo-P3. Exploratory analysis revealed a late sustained parietal negativity to errors in patients as compared to controls. Taken together, the present findings emphasize the importance of social context for the processes underlying performance monitoring. However, the notion of altered error monitoring reflected in an altered ERN in SAD is not supported by our data.
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http://dx.doi.org/10.1016/j.biopsycho.2017.11.003DOI Listing
February 2018

In vivo precision of the GE lunar iDXA for the assessment of lumbar spine, total hip, femoral neck, and total body bone mineral density in severely obese patients.

J Clin Densitom 2014 Jan-Mar;17(1):109-15. Epub 2013 Jul 26.

Department of Kinesiology and Physical Education, McGill University, Montreal, QC, Canada. Electronic address:

No study has evaluated the precision of the GE Lunar iDXATM (GE Healthcare) in measuring bone mineral density (BMD) among severely obese patients. The purpose of the study was to evaluate the precision of the GE Lunar iDXATM for assessing BMD, including the lumbar spine L1-L4, L2-L4, the total hip, femoral neck, and total body in a severely obese population (body mass index [BMI]>40 kg/m(2)). Sixty-four severely obese participants with a mean age of 46 ± 11 yr, BMI of 49 ± 6 kg/m(2), and a mean body mass of 136.8 ± 20.4 kg took part in this investigation. Two consecutive iDXA scans (with repositioning) of the total body (total body BMD [TBBMD]), lumbar spine (L1-L4 and L2-L4), total hip (total hip BMD [THBMD]), and femoral neck (femoral neck BMD [FNBMD]) were conducted for each participant. The coefficient of variation (CV), the root mean square (RMS) averages of standard deviations of repeated measurements, the corresponding 95% least significant change, and intraclass correlations (ICCs) were calculated. In addition, analysis of bias and coefficients of repeatability were calculated. The results showed a high level of precision for total body (TBBMD), lumbar spine (L1-L4), and total hip (THBMD) with values of RMS: 0.013, 0.014, and 0.011 g/cm(2); CV: 0.97%, 1.05%, and 0.99%, respectively. Precision error for the femoral neck was 2.34% (RMS: 0.025 g/cm(2)) but still represented high reproducibility. ICCs in all dual-energy X-ray absorptiometry measurements were 0.99 with FNBMD having the lowest at 0.98. Coefficients of repeatability for THBMD, FNBMD, L1-L4, L2-L4, and TBBMD were 0.0312, 0.0688, 0.0383, 0.0493, and 0.0312 g/cm(2), respectively. The Lunar iDXA demonstrated excellent precision for BMD measurements and is the first study to assess reproducibility of the GE Lunar iDXA with severely obese adults.
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http://dx.doi.org/10.1016/j.jocd.2013.06.001DOI Listing
April 2014