Publications by authors named "Tina Meller"

23 Publications

  • Page 1 of 1

Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity.

Psychol Med 2021 Apr 8:1-12. Epub 2021 Apr 8.

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

Background: MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.

Methods: We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.

Results: The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.

Conclusions: Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291721001082DOI Listing
April 2021

Subclinical schizotypal vs. autistic traits show overlapping and diametrically opposed facets in a non-clinical population.

Schizophr Res 2021 Mar 18;231:32-41. Epub 2021 Mar 18.

Cognitive Neuropsychiatry Lab, Department of Psychiatry and Psychotherapy, Philipps Universität Marburg, Marburg, Germany; Center for Mind, Brain, and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, Germany; Marburg University Hospital - UKGM, Marburg, Germany.

Background: The overlap of autism spectrum disorder (ASD) and psychosis or schizophrenia spectrum disorders (SSD) has exposed problems central to conceptualising and understanding co-morbidity in psychiatric disorders.

Methods: In the present study, we demonstrate that a deep phenotyping approach aids clarification of both overlapping and diametrically opposed features of ASD and SSD on the level of trait facets.

Results: We first show overlap of negative and disorganised (but not positive) features of schizotypy with autistic traits in a sample of n = 376 German non-clinical subjects using multiple psychometric measures of schizotypy (MSS multidimensional schizotypy scale, OLIFE Oxford-Liverpool Inventory of Feelings and Experiences, and SPQ-B schizotypal personality questionnaire - brief) and the AQ autism spectrum quotient, with control measures for affective spectrum pathology (BDI). Findings were then replicated in a French-Swiss sample (n = 264) using MSS, OLIFE, AQ, and in addition the Community Assessment of Psychic Experiences (CAPE). Additional principal component analysis confirmed our finding of the co-existence of both overlapping (loss of function, social communication deficit, and negative schizotypy) as well as diametrically opposed features (AQ attention to detail, positive schizotypy) across the two spectra. Results were validated with Horn's parallel analyses, affirming two component solutions, and PCA using sample-specific, factor-analysis-derived schizotypy scores.

Conclusions: Providing a framework for multi-dimensional transdiagnostic characterisation of ASD vs. SSD phenotypes we point out overlapping vs. discriminating facets. In addition to the use of novel multidimensional schizotypy scales, it also shows transcultural consistency of findings, and highlights a particular role for the attention to detail AQ subscale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.02.018DOI Listing
March 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, University of Muenster, Germany Albert-Schweitzer-Campus 1 Gebäude A9, 48149 Münster, Germany.

Background: Major depressive disorder (MDD) and type 2 diabetes (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 so, 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 MDD patients and 539 healthy controls.

Results: Polygenic risk score for T2D across MDD patients and healthy controls 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 FA variation may mediate the association between PGS 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 MDD patients and healthy controls, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpsc.2021.02.010DOI Listing
March 2021

Associations of subclinical autistic-like traits with brain structural variation using diffusion tensor imaging and voxel-based morphometry.

Eur Psychiatry 2021 Mar 3;64(1):e27. Epub 2021 Mar 3.

Cognitive Neuropsychiatry Lab, Department of Psychiatry and Psychotherapy, Philipps-University Marburg/Marburg University Hospital-UKGM, Marburg, Germany.

Background: Previous case-control studies of autistic spectrum disorder (ASD) have identified altered brain structure such as altered frontal and temporal cortex volumes, or decreased fractional anisotropy (FA) within the inferior fronto-occipital fasciculus in patients. It remains unclear whether subclinical autistic-like traits might also be related to variation in these brain structures.

Methods: In this study, we analyzed magnetic resonance imaging (MRI) data of 250 psychiatrically healthy subjects phenotyped for subclinical autistic-like traits using the Autism Spectrum Quotient (AQ). For data analysis, we used voxel-based morphometry of T1-MRIs (Computational Anatomy Toolbox) and tract-based spatial statistics for diffusion tensor imaging data.

Results: AQ attention switching subscale correlated negatively with FA values in the bilateral uncinate fasciculus as well as the bilateral inferior fronto-occipital fasciculus. Higher AQ attention switching subscale scores were associated with increased mean diffusivity and radial diffusivity values in the uncinate fasciculus, while axial diffusivity values within this tract show a negative correlation. AQ attention to detail subscale correlated positively with gray matter volume in the right pre- and postcentral gyrus.

Conclusions: We demonstrate that individuals with higher levels of autism-spectrum-like features show decreased white matter integrity in tracts associated with higher-level visual processing and increased cortical volume in areas linked to movement sequencing and working memory. Our results resemble regional brain structure alterations found in individuals with ASD. This offers opportunities to further understand the etiology and pathogenesis of the disorder and shows a subclinical continuum perspective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1192/j.eurpsy.2021.15DOI 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 Feb 26. Epub 2021 Feb 26.

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2021.02.006DOI Listing
February 2021

Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals.

Eur Arch Psychiatry Clin Neurosci 2021 Feb 2. Epub 2021 Feb 2.

Cognitive Neuropsychiatry Lab, Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.

In the general population, psychosis risk phenotypes occur independently of attenuated prodromal syndromes. Neurobiological correlates of vulnerability could help to understand their meaningfulness. Interactions between the occurrence of psychotic-like experiences (PLE) and other psychological factors e.g., distress related to PLE, may distinguish psychosis-prone individuals from those without risk of future psychotic disorder. We aimed to investigate whether (a) correlates of total PLE and distress, and (b) symptom dimension-specific moderation effects exist at the brain structural level in non-help-seeking adults reporting PLE below and above the screening criterion for clinical high-risk (CHR). We obtained T1-weighted whole-brain MRI scans from 104 healthy adults from the community without psychosis CHR states for voxel-based morphometry (VBM). Brain structural associations with PLE and PLE distress were analysed with multiple linear regression models. Moderation of PLE by distress severity of two types of positive symptoms from the Prodromal Questionnaire (PQ-16) screening inventory was explored in regions-of-interest after VBM. Total PQ-16 score was positively associated with grey matter volume (GMV) in prefrontal regions, occipital fusiform and lingual gyri (p < 0.05, FDR peak-level corrected). Overall distress severity and GMV were not associated. Examination of distress severity on the positive symptom dimensions as moderators showed reduced strength of the association between PLE and rSFG volume with increased distress severity for perceptual PLE. In this study, brain structural variation was related to PLE level, but not distress severity, suggesting specificity. In healthy individuals, positive relationships between PLE and prefrontal volumes may indicate protective features, which supports the insufficiency of PLE for the prediction of CHR. Additional indicators of vulnerability, such as distress associated with perceptual PLE, change the positive brain structure relationship. Brain structural findings may strengthen clinical objectives through disentanglement of innocuous and risk-related PLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-020-01229-5DOI Listing
February 2021

Cortical Complexity in People at Ultra-High-Risk for Psychosis Moderated by Childhood Trauma.

Front Psychiatry 2020 10;11:594466. Epub 2020 Nov 10.

Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg and Marburg University Hospital, Marburg, Germany.

Subjects with ultra-high risk (UHR) states for psychosis show brain structural volume changes similar to first-episode psychosis and also elevated incidence of environmental risk factors like childhood trauma. It is unclear, however, whether early neurodevelopmental trajectories are altered in UHR. We screened a total of 12,779 first-year Chinese students to enroll 36 UHR subjects (based on clinical interviews) and 59 non-UHR healthy controls for a case-control study of markers of early neurodevelopment. Subjects underwent 3T MRI scanning and clinical characterization, including the childhood trauma questionnaire (CTQ). We then used the CAT12 toolbox to analyse structural brain scans for cortical surface complexity, a spherical harmonics-based marker of early neurodevelopmental changes. While we did not find statistically significant differences between the groups, a trend level finding for reduced cortical complexity (CC) in UHR vs. non-UHR subjects emerged in the left superior temporal cortex (and adjacent insular and transverse temporal cortices), and this trend level association was significantly moderated by childhood trauma (CTQ score). Our findings indicate that UHR subjects tend to show abnormal cortical surface morphometry, in line with recent research; more importantly, however, this association seems to be considerably modulated by early environmental impacts. Hence, our results provide an indication of environmental or gene × environment interactions on early neurodevelopment leading up to elevated psychosis risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2020.594466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685197PMC
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291720002950DOI Listing
September 2020

Childhood maltreatment and adult mental disorders - the prevalence of different types of maltreatment and associations with age of onset and severity of symptoms.

Psychiatry Res 2020 11 30;293:113398. Epub 2020 Aug 30.

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.

Childhood maltreatment (CM) is a risk factor for numerous mental disorders. However, the specificity of CM types in mental disorders is still being discussed. The present study examined the prevalence of five CM types in patients with schizophrenia/schizoaffective disorder (SZ; n = 107), bipolar disorder (BD; n = 103), depression (MDD; n = 604; with the two subgroups Persistent Depressive Disorder (PDD) and non-chronic MDD), and in healthy controls (HC; n = 715). Additionally, associations between CM types, symptom severity, and age of onset were investigated. The prevalence of all CM types was higher in the patient groups compared to HC. Emotional neglect, emotional abuse, and physical neglect were reported most frequently in all groups. Notably, patients with PDD reported more CM of all types than patients with non-chronic MDD. The severity of depression was associated with emotional abuse and neglect; anxiety with emotional abuse, emotional neglect, and sexual abuse; positive SZ symptoms with physical neglect; negative symptoms with emotional and physical neglect; and mania with sexual abuse and physical neglect. CM was associated with a younger age of onset in MDD and BD. The high prevalence of CM in patients with severe mental disorders highlights the importance of considering this issue in the treatment of such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2020.113398DOI Listing
November 2020

Childhood maltreatment and cognitive functioning: the role of depression, parental education, and polygenic predisposition.

Neuropsychopharmacology 2021 Apr 14;46(5):891-899. Epub 2020 Aug 14.

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

Childhood maltreatment is associated with cognitive deficits that in turn have been predictive for therapeutic outcome in psychiatric patients. However, previous studies have either investigated maltreatment associations with single cognitive domains or failed to adequately control for confounders such as depression, socioeconomic environment, and genetic predisposition. We aimed to isolate the relationship between childhood maltreatment and dysfunction in diverse cognitive domains, while estimating the contribution of potential confounders to this relationship, and to investigate gene-environment interactions. We included 547 depressive disorder and 670 healthy control participants (mean age: 34.7 years, SD = 13.2). Cognitive functioning was assessed for the domains of working memory, executive functioning, processing speed, attention, memory, and verbal intelligence using neuropsychological tests. Childhood maltreatment and parental education were assessed using self-reports, and psychiatric diagnosis was based on DSM-IV criteria. Polygenic scores for depression and for educational attainment were calculated. Multivariate analysis of cognitive domains yielded significant associations with childhood maltreatment (η² = 0.083, P < 0.001), depression (η² = 0.097, P < 0.001), parental education (η² = 0.085, P < 0.001), and polygenic scores for depression (η² = 0.021, P = 0.005) and educational attainment (η² = 0.031, P < 0.001). Each of these associations remained significant when including all of the predictors in one model. Univariate tests revealed that maltreatment was associated with poorer performance in all cognitive domains. Thus, environmental, psychopathological, and genetic risk factors each independently affect cognition. The insights of the current study may aid in estimating the potential impact of different loci of interventions for cognitive dysfunction. Future research should investigate if customized interventions, informed by individual risk profiles and related cognitive preconditions, might enhance response to therapeutic treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-020-00794-6DOI Listing
April 2021

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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291720002822DOI Listing
August 2020

Anterior vs Posterior Hippocampal Subfields in an Extended Psychosis Phenotype of Multidimensional Schizotypy in a Nonclinical Sample.

Schizophr Bull 2021 Jan;47(1):207-218

Cognitive Neuropsychiatry Lab, Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.

Numerous studies have implicated involvement of the hippocampus in the etiology and expression of schizophrenia-spectrum psychopathology, and reduced hippocampal volume is one of the most robust brain abnormalities reported in schizophrenia. Recent studies indicate that early stages of schizophrenia are specifically characterized by reductions in anterior hippocampal volume; however, studies have not examined hippocampal volume reductions in subclinical schizotypy. The present study was the first to examine the associations of positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults, phenotyped using the Multidimensional Schizotypy Scale (MSS). Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres. We demonstrate differential spatial effects across anterior vs posterior hippocampus segments across different dimensions of the schizotypy risk phenotype. The interaction of negative and disorganized schizotypy robustly predicted left hemisphere volumetric reductions for the anterior and total hippocampus, and anterior CA and DG, and the largest reductions were seen in participants high in negative and disorganized schizotypy. These findings extend previous early psychosis studies and together with behavioral studies of hippocampal-related memory impairments provide the basis for a dimensional neurobiological hippocampal model of schizophrenia risk. Subtle hippocampal subfield volume reductions may be prevalent prior to the onset of detectable prodromal clinical symptoms of psychosis and play a role in the etiology and development of such conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbaa099DOI Listing
January 2021

Brain structural correlates of schizotypal signs and subclinical schizophrenia nuclear symptoms in healthy individuals.

Psychol Med 2020 Jun 24:1-10. Epub 2020 Jun 24.

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

Background: Subclinical psychotic-like experiences (PLE), resembling key symptoms of psychotic disorders, are common throughout the general population and possibly associated with psychosis risk. There is evidence that such symptoms are also associated with structural brain changes.

Methods: In 672 healthy individuals, we assessed PLE and associated distress with the symptom-checklist-90R (SCL-90R) scales 'schizotypal signs' (STS) and 'schizophrenia nuclear symptoms' (SNS) and analysed associations with voxel- and surfaced-based brain structural parameters derived from structural magnetic resonance imaging at 3 T with CAT12.

Results: For SNS, we found a positive correlation with the volume in the left superior parietal lobule and the precuneus, and a negative correlation with the volume in the right inferior temporal gyrus [p < 0.05 cluster-level Family Wise Error (FWE-corrected]. For STS, we found a negative correlation with the volume of the left and right precentral gyrus (p < 0.05 cluster-level FWE-corrected). Surface-based analyses did not detect any significant clusters with the chosen statistical threshold of p < 0.05. However, in exploratory analyses (p < 0.001, uncorrected), we found a positive correlation of SNS with gyrification in the left insula and rostral middle frontal gyrus and of STS with the left precuneus and insula, as well as a negative correlation of STS with gyrification in the left temporal pole.

Conclusions: Our results show that brain structures in areas implicated in schizophrenia are also related to PLE and its associated distress in healthy individuals. This pattern supports a dimensional model of the neural correlates of symptoms of the psychotic spectrum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291720002044DOI Listing
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.04.041DOI Listing
August 2020

Intermittent theta-burst stimulation moderates interaction between increment of N-Acetyl-Aspartate in anterior cingulate and improvement of unipolar depression.

Brain Stimul 2020 Jul - Aug;13(4):943-952. Epub 2020 Mar 27.

Department of Psychiatry and Psychotherapy, University of Marburg, Germany; Marburg Center for Mind, Brain and Behavior, MCMBB, University of Marburg, Germany.

Background: Intermittent theta-burst stimulation (iTBS), a novel repetitive transcranial magnetic stimulation (rTMS) technique, appears to have antidepressant effects when applied over left dorsolateral prefrontal cortex (DLPFC). However, its underlying neurobiological mechanisms are unclear. Proton magnetic resonance spectroscopy (H-MRS) provides in vivo measurements of cerebral metabolites altered in major depressive disorder (MDD) like N-acetyl-aspartate (NAA) and choline-containing compounds (Cho). We used MRS to analyse effects of iTBS on the associations between the shifts in the NAA and Cho levels during therapy and MDD improvement.

Methods: In-patients with unipolar MDD (N = 57), in addition to treatment as usual, were randomized to receive 20 iTBS or sham stimulations applied over left DLPFC over four weeks. Single-voxel H-MRS of the anterior cingulate cortex (ACC) was performed at baseline and follow-up. Increments of concentrations, as well as MDD improvement, were defined as endpoints. We tested a moderated mediation model of effects using the PROCESS macro (an observed variable ordinary least squares and logistic regression path analysis modeling tool) for SPSS.

Results: Improvement of depressive symptoms was significantly associated with decrease of Cho/NAA ratio, mediated by NAA. iTBS had a significant moderating effect enhancing the relationship between NAA change and depression improvement.

Conclusions: Our findings suggest a potential neurochemical pathway and mechanisms of antidepressant action of iTBS, which may moderate the improvement of metabolic markers of neuronal viability. iTBS might increase neuroplasticity, thus facilitating normalization of neuronal circuit function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2020.03.015DOI Listing
December 2020

Factor analyses of multidimensional symptoms in a large group of patients with major depressive disorder, bipolar disorder, schizoaffective disorder and schizophrenia.

Schizophr Res 2020 04 17;218:38-47. Epub 2020 Mar 17.

Department of Psychiatry und Psychotherapy, University of Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Germany.

Background: There is an ongoing discussion about which neurobiological correlates or symptoms separate the major psychoses (i.e. Major Depressive Disorder MDD, Bipolar Disorder BD, and Schizophrenia SZ). Psychopathological factor analyses within one of these disorders have resulted in models including one to five factors. Factor analyses across the major psychoses using a comprehensive set of psychopathological scales in the same patients are lacking. It is further unclear, whether hierarchical or unitarian models better summarize phenomena.

Method: Patients (n = 1182) who met DSM-IV criteria for MDD, BD, SZ or schizoaffective disorder were assessed with the SANS, SAPS, HAMA, HAM-D, and YMRS. The sample was split into two and analyzed using explorative and confirmatory factor analyses to extract psychopathological factors independent of diagnosis.

Results: In the exploratory analysis of sample 1 (n = 593) we found 5 factors. The confirmatory analysis using sample 2 (n = 589) confirmed the 5-factor model (χ = 1287.842, df = 571, p < .0001: CFI = 0.932; RMSEA = 0.033). The 5-factors were depression, negative syndrome, positive formal thought disorder, paranoid-hallucinatory syndrome, and increased appetite. Increased appetite was not related to medication. None of the factors was specific for one diagnosis. Second order factor analysis revealed two higher order factors: negative/affective (I) and positive symptoms (II).

Conclusion: This is the first study delineating psychopathological factors in a large group of patients across the spectrum of affective and psychotic disorders. In future neurobiological studies, we should consider transdiagnostic syndromes besides the traditional diagnoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2020.03.011DOI Listing
April 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-019-0603-1DOI Listing
July 2020

The association of striatal volume and positive schizotypy in healthy subjects: intelligence as a moderating factor.

Psychol Med 2020 10 18;50(14):2355-2363. Epub 2019 Sep 18.

Cognitive Neuropsychiatry lab, Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039Marburg, Germany.

Background: Schizotypy, a putative schizophrenia endophenotype, has been associated with brain-structural variations partly overlapping with those in psychotic disorders. Variations in precuneus structure have been repeatedly reported, whereas the involvement of fronto-striatal networks - as in schizophrenia - is less clear. While shared genetic architecture is thought to increase vulnerability to environmental insults, beneficial factors like general intelligence might buffer their effect.

Methods: To further investigate the role of fronto-striatal networks in schizotypy, we examined the relationship of voxel- and surface-based brain morphometry and a measure of schizotypal traits (Schizotypal Personality Questionnaire, with subscores Cognitive-Perceptual, Interpersonal, Disorganised) in 115 healthy participants [54 female, mean age (s.d.) = 27.57(8.02)]. We tested intelligence (MWT-B) as a potential moderator.

Results: We found a positive association of SPQ Cognitive-Perceptual with putamen volume (p = 0.040, FWE peak level-corrected), moderated by intelligence: with increasing IQ, the correlation of SPQ Cognitive-Perceptual and striatal volume decreased (p = 0.022). SPQ Disorganised was positively correlated with precentral volume (p = 0.013, FWE peak level-corrected). In an exploratory analysis (p < 0.001, uncorrected), SPQ total score was positively associated with gyrification in the precuneus and postcentral gyrus, and SPQ Disorganised was negatively associated with gyrification in the inferior frontal gyrus.

Conclusions: Our findings support the role of fronto-striatal networks for schizotypal features in healthy individuals, and suggest that these are influenced by buffering factors like intelligence. We conclude that protective factors, like general cognitive capacity, might attenuate the psychosis risk associated with schizotypy. These results endorse the idea of a continuous nature of schizotypy, mirroring similar findings in schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291719002459DOI Listing
October 2020

Reduced fractional anisotropy in depressed patients due to childhood maltreatment rather than diagnosis.

Neuropsychopharmacology 2019 11 5;44(12):2065-2072. Epub 2019 Aug 5.

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

Reduced fractional anisotropy (FA) associated with Major Depressive Disorder (MDD) overlaps anatomically with effects of childhood maltreatment experiences. The aim of this study was, therefore, to replicate the negative effect of childhood maltreatment on white matter fiber structure and to demonstrate, that alterations in MDD might be partially attributed to the higher occurrence of childhood maltreatment in MDD. Two independent cohorts (total N = 1 256) were investigated in a diffusion tensor imaging study: The Münster Neuroimaging Cohort (MNC, N = 186 MDD, N = 210 healthy controls, HC) as discovery sample and the Marburg-Münster Affective Disorders Cohort Study (MACS, N = 397 MDD, N = 462 HC) as replication sample. The effects of diagnosis (HC vs. MDD) and Childhood Trauma Questionnaire (CTQ) scores on FA were analyzed. A main effect of diagnosis with higher FA in MDD patients compared with HC was found in the MNC (p = 0.021), but not in the MACS (p = 0.52) before correcting for CTQ. A significant negative correlation of FA with CTQ emerged in both cohorts (MNC: p = 0.006, MACS: p = 0.012) in several tracts previously described in the literature. No CTQ × diagnosis interaction could be detected. Any main effect of diagnosis was abolished after correcting for CTQ (MNC: p = 0.562, MACS: p = 0.115). No differences in FA between MDD and HC could be found after correcting for childhood maltreatment, suggesting that previously reported group differences might be attributed partially to higher levels of maltreatment experiences in MDD rather than diagnosis itself. Furthermore, a well-established finding of reduced FA following childhood maltreatment experiences was replicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-019-0472-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897978PMC
November 2019

Apolipoprotein E Homozygous ε4 Allele Status: A Deteriorating Effect on Visuospatial Working Memory and Global Brain Structure.

Front Neurol 2019 27;10:552. Epub 2019 May 27.

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

The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ε4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. A sample of = 31 homozygous ε4 carriers was contrasted with = 31 non-ε4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; = 13.48; 51.6% female). Among them were = 12 homozygous ε4 carriers and = 12 non-ε4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. Homozygous ε4 carriers showed significantly lower Corsi span capacity than non-ε4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. Our results point toward a negative association of homozygous ε4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.00552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545528PMC
May 2019

Associations of schizophrenia risk genes ZNF804A and CACNA1C with schizotypy and modulation of attention in healthy subjects.

Schizophr Res 2019 06 7;208:67-75. Epub 2019 May 7.

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

Schizotypy is a multidimensional risk phenotype distributed in the general population, constituting of subclinical, psychotic-like symptoms. It is associated with psychosis proneness, and several risk genes for psychosis are associated with schizotypy in non-clinical populations. Schizotypy might also modulate cognitive abilities as it is associated with attentional deficits in healthy subjects. In this study, we tested the hypothesis that established genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737 are associated with psychometric schizotypy and that schizotypy mediates their effect on attention or vice versa. In 615 healthy subjects from the FOR2107 cohort study, we analysed the genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737, psychometric schizotypy (schizotypal personality questionnaire-brief SPQB), and a neuropsychological measure of sustained and selective attention (d2 test). ZNF804A rs1344706 C (non-risk) alleles were significantly associated with higher SPQ-B Cognitive-Perceptual subscores in women and with attention deficits in both sexes. This schizotypy dimension also mediated the effect of ZNF804A on attention in women, but not in men. CACNA1C rs1006737-A showed a significant sex-modulated negative association with Interpersonal schizotypy only in men, and no effect on attention. Our multivariate model demonstrates differential genetic contributions of two psychosis risk genes to dimensions of schizotypy and, partly, to attention. This supports a model of shared genetic influence between schizotypy and cognitive functions impaired in schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2019.04.018DOI Listing
June 2019

Efficacy of Systolic Extinction Training in Fibromyalgia Patients With Elevated Blood Pressure Response to Stress: A Tailored Randomized Controlled Trial.

Arthritis Care Res (Hoboken) 2019 05;71(5):678-688

Center for Pain Research on Impact, Measurement, and Effectiveness, University of Washington, Seattle.

Objective: An intrinsic pain regulatory system is modulated by both cardiovascular dynamics that influence baroreflex sensitivity (BRS) and is diminished in fibromyalgia (FM). Baroreceptors relay cardiovascular output to the dorsal medial nucleus tractus solitarius reflex arcs that regulate pain, sleep, anxiety, and blood pressure. The aim of this study was to evaluate the effects of systolic extinction training (SET), which combines operant treatment (OT) with baroreflex training (BRT). BRT delivers peripheral electrical stimulation within a few milliseconds of the systolic or diastolic peak in the cardiac cycle. In addition, we compared SET to OT-transcutaneous electrical stimulation (TENS) independent of the cardiac cycle and aerobic exercise (AE)-BRT in FM patients with elevated blood pressure responses to stress.

Methods: Sixty-two female patients with FM were randomized to receive either SET (n = 21), OT-TENS (n = 20), or AE-BRT (n = 21). Outcome assessments were performed before treatment (T1), after 5 weeks of treatment (T2), and after the 12-month follow-up (T3).

Results: In contrast to patients receiving OT-TENS or AE-BRT, those receiving SET reported a significantly greater reduction in pain and pain interference (all P < 0.01) that was maintained at the 12-month follow-up. Clinically meaningful pain reduction at T3 was achieved in 82% of patients in the SET group, 39% of those in the OT-TENS group, and only 14% of those in the AE-BRT group. Patients in the SET group showed a significant increase (57%) in BRS following treatment, while neither the AE-BRT group or the OT-TENS group showed significant changes over time.

Conclusion: SET resulted in statistically significant, clinically meaningful, and long-lasting pain remission and interference compared to OT-TENS and AE-BRT. These results suggest that BRS modification is the primary mechanism of improvement. Replication of our results using larger samples and extension to other chronic pain conditions appear to be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.23615DOI Listing
May 2019

Neural Correlates of Human Echolocation of Path Direction During Walking.

Multisens Res 2015 ;28(1-2):195-226

Echolocation can be used by blind and sighted humans to navigate their environment. The current study investigated the neural activity underlying processing of path direction during walking. Brain activity was measured with fMRI in three blind echolocation experts, and three blind and three sighted novices. During scanning, participants listened to binaural recordings that had been made prior to scanning while echolocation experts had echolocated during walking along a corridor which could continue to the left, right, or straight ahead. Participants also listened to control sounds that contained ambient sounds and clicks, but no echoes. The task was to decide if the corridor in the recording continued to the left, right, or straight ahead, or if they were listening to a control sound. All participants successfully dissociated echo from no echo sounds, however, echolocation experts were superior at direction detection. We found brain activations associated with processing of path direction (contrast: echo vs. no echo) in superior parietal lobule (SPL) and inferior frontal cortex in each group. In sighted novices, additional activation occurred in the inferior parietal lobule (IPL) and middle and superior frontal areas. Within the framework of the dorso-dorsal and ventro-dorsal pathway proposed by Rizzolatti and Matelli (2003), our results suggest that blind participants may automatically assign directional meaning to the echoes, while sighted participants may apply more conscious, high-level spatial processes. High similarity of SPL and IFC activations across all three groups, in combination with previous research, also suggest that all participants recruited a multimodal spatial processing system for action (here: locomotion).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1163/22134808-00002491DOI Listing
September 2015