Malte S. Depping

Abnormal gray and white matter volume in delusional infestation.

Little is known about the neural basis of delusional infestation (DI), the delusional belief to be infested with pathogens. Case series and the response to anti-dopaminergic medication indicate disruptions in dopaminergic neurotransmission in the striatum (caudate, putamen), but did not allow for population-based inference. Here, we report the first whole-brain structural neuroimaging study to investigate gray and white matter abnormalities in DI compared to controls. In this study, we used structural magnetic resonance imaging and voxel-based morphometry to investigate gray and white matter volume in 16 DI patients and 16 matched healthy controls. Lower gray matter volume in DI patients compared to controls was found in left medial, lateral and right superior frontal cortices, left anterior cingulate cortex, bilateral insula, left thalamus, right striatal areas and in lateral and medial temporal cortical regions (p<0.05, cluster-corrected). Higher white matter volume in DI patients compared to controls was found in right middle cingulate, left frontal opercular and bilateral striatal regions (p<0.05, cluster-corrected). This study shows that structural changes in prefrontal, temporal, insular, cingulate and striatal brain regions are associated with DI, supporting a neurobiological model of disrupted prefrontal control over somato-sensory representations.

Visual system integrity and cognition in early Huntington's disease

Posterior cortical volume changes and abnormal visuomotor performance are present in patients with Huntingtons disease (HD). However, it is unclear whether posterior cortical volume loss contributes to abnormal neural activity, and whether activity changes predict cognitive dysfunction. Using magnetic resonance imaging (MRI), we investigated brain structure and visual network activity at rest in patients with early HD (n = 20) and healthy controls (n = 20). The symbol digit modalities test (SDMT) and subtests of the Visual Object and Space Perception Battery were completed offline. For functional MRI data, a group independent component analysis was used. Voxel‐based morphometry was employed to assess regional brain atrophy, and ‘biological parametric mapping’ analyses were included to investigate the impact of atrophy on neural activity. Patients showed significantly worse visuomotor and visual object performance than controls. Structural analyses confirmed occipitotemporal atrophy. In patients and controls, two spatiotemporally distinct visual systems were identified. Patients showed decreased activity in the left fusiform cortex, and increased left cerebellar activity. These findings remained stable after correction for brain atrophy. Lower fusiform cortex activity was associated with lower SDMT performance and with higher disease burden scores. These associations were absent when cerebellar function was related to task performance and disease burden. The results of this study suggest that regionally specific functional abnormalities of the visual system can account for the worse visuomotor cognition in HD patients. However, occipital volume changes cannot sufficiently explain abnormal neural function in these patients.

Specificity of abnormal brain volume in major depressive disorder: A comparison with borderline personality disorder

BACKGROUND Abnormal brain volume has been frequently demonstrated in major depressive disorder (MDD). It is unclear if these findings are specific for MDD since aberrant brain structure is also present in disorders with depressive comorbidity and affective dysregulation, such as borderline personality disorder (BPD). In this transdiagnostic study, we aimed to investigate if regional brain volume loss differentiates between MDD and BPD. Further, we tested for associations between brain volume and clinical variables within and between diagnostic groups. METHODS 22 Females with a DSM-IV diagnosis of MDD, 17 females with a DSM-IV diagnosis of BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls (HC) were investigated using magnetic resonance imaging. High-resolution structural data were analyzed using voxel-based morphometry. RESULTS A significant (p<0.05, cluster-corrected) volume decrease of the anterior cingulate cortex (ACC) was found in MDD compared to HC, as opposed to volume decreases of the amygdala in BPD compared to both HC and MDD. Sensitivity and specificity of regional gray matter volume for a diagnosis of MDD were modest to fair. Amygdala volume was related to depressive symptoms across the entire patient sample. LIMITATIONS Potential limitations of this study include the modest sample size and the heterogeneous psychotropic drug treatment. CONCLUSIONS ACC volume reduction is more pronounced in MDD with an intermediate degree of volume loss in BPD compared to HC. In contrast, amygdala volume loss is more pronounced in BPD compared to MDD, yet amygdala volume is associated with affective symptom expression in both disorders.

Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy.

Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). In schizophrenia (SZ), ECT is frequently considered in drug-resistant cases, as an augmentation of antipsychotic treatment or in cases when rapid symptom relief is indicated. Accumulating neuroimaging evidence suggests modulation of medial temporal lobe and prefrontal cortical regions in MDD by ECT. In SZ, ECT-effects on brain structure have not been systematically investigated so far. In this study, we investigated brain volume in 21 ECT-naïve patients (12 with MDD, 9 with SZ) who received right-sided unilateral ECT. Twenty-one healthy controls were included. Structural magnetic resonance imaging data were acquired before and after ECT. Healthy participants were scanned once. Source-based morphometry was used to investigate modulation of structural networks pre/post ECT. ECT had an impact on distinct structural networks in MDD and SZ. In both MDD and SZ SBM revealed a medial temporal lobe (MTL) network (including hippocampus and parahippocampal cortex) which showed a significant increase after ECT. The increase in MTL network strength was not associated with clinical improvement in either MDD or SZ. In SZ a lateral prefrontal/cingulate cortical network showed a volume increase after ECT, and this effect was accompanied by clinical improvement. These findings provide preliminary evidence for structural network change in response to ECT in MDD and SZ. The data suggest both diagnosis-specific and transdiagnostic ECT-effects on brain volume. In contrast to SZ, in MDD structural network modulation by ECT was not associated with clinical improvement.

Cerebellar volume change in response to electroconvulsive therapy in patients with major depression.

&NA; Electroconvulsive therapy (ECT) is remarkably effective in severe major depressive disorder (MDD). Growing evidence has accumulated for brain structural and functional changes in response to ECT, primarily within cortico‐limbic regions that have been considered in current neurobiological models of MDD. Despite increasing evidence for important cerebellar contributions to affective, cognitive and attentional processes, investigations on cerebellar effects of ECT in depression are yet lacking. In this study, using cerebellum‐optimized voxel‐based analysis methods, we investigated cerebellar volume in 12 MDD patients who received right‐sided unilateral ECT. 16 healthy controls (HC) were included. Structural MRI data was acquired before and after ECT and controls were scanned once. Baseline structural differences in MDD compared to HC were located within the “cognitive cerebellum” and remained unchanged with intervention. ECT led to gray matter volume increase of left cerebellar area VIIa crus I, a region ascribed to the “affective/limbic cerebellum”. The effects of ECT on cerebellar structure correlated with overall symptom relief. These findings provide preliminary evidence that structural change of the cerebellum in response to ECT may be related to the treatments antidepressant effects. HighlightsWe investigate cerebellar volume in response to ECT in major depression.ECT induces volume increase in “non‐motor” cerebellar regions.Cerebellar volume change following ECT is associated with clinical improvement.ECT may enable structural neuroplasticity within the “affective cerebellum”.

Common and distinct structural network abnormalities in major depressive disorder and borderline personality disorder

Major depressive disorder (MDD) and borderline personality disorder (BPD) show substantial overlap in both affective symptom expression and in regional brain volume reduction. To address the specificity of structural brain change for the respective diagnostic category, we investigated structural networks in MDD and BPD to identify shared and distinct patterns of abnormal brain volume associated with these phenotypically related disorders. Using magnetic resonance imaging at 3 T, we studied 22 females with MDD, 17 females with BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls. We used “source-based morphometry” (SBM) to investigate naturally grouping patterns of gray matter volume variation (i.e. “structural networks”) and the magnitude of their expression between groups. SBM identified three distinct structural networks which showed a significant group effect (p b 0.05, FDR-corrected). A bilateral frontostriatal network showed reduced volume in MDD compared to both controls and BPD patients. A medial temporal/medial frontal network was found to be significantly reduced in BPD compared to both controls and MDD patients. Decreased cingulate and lateral prefrontal volume was found in both MDD and BPD when compared to healthy individuals. In MDD significant relationships were found between depressive symptoms and a cingulate/lateral prefrontal structural pattern. In contrast, overall BPD symptoms and impulsivity scores were significantly associated with medial temporal/medial frontal network volume. The data suggest both distinct and common patterns of abnormal brain volume in MDD and BPD. Alterations of distinct structural networks differentially modulate clinical symptom expression in these disorders.

Abnormal cerebellar volume in acute and remitted major depression.

Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well.

Neuromodulation in response to electroconvulsive therapy in schizophrenia and major depression

BACKGROUND Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). ECT has been also shown to be effective in schizophrenia (SZ), particularly when rapid symptom reduction is needed or in cases of resistance to drug-treatment. However, its precise mechanisms of action remain largely unknown. OBJECTIVE/HYPOTHESIS This study examined whether ECT exerts disorder-specific or unspecific modulation of brain structure and function in SZ and MDD. METHODS We investigated neuromodulatory effects of right-sided unilateral ECT in pharmacoresistant patients with SZ or MDD. Magnetic resonance imaging was conducted before and after ECT to investigate treatment-related effects on brain structure and function. Imaging data were analyzed by means of Voxel Based Morphometry and Resting State Functional Connectivity (RSFC) methods. RESULTS Right unilateral ECT induced transdiagnostic regional increases of limbic gray matter and modulations of neural coupling at rest. Structural effects were accompanied by a decrease in RSFC within temporoparietal, prefrontal and cortical midline structures, and an increase in hypothalamic RSFC. The extent of structural and functional change was partially inversely associated with the baseline measures. CONCLUSION The present findings provide first evidence for transdiagnostic changes of brain structure together with modulation of brain function after ECT. The data indicate diagnosis-unspecific mechanisms of action with respect to regional gray matter volume and resting-state functional connectivity.

Aberrant cortical neurodevelopment in major depressive disorder

BACKGROUND There is strong neuroimaging evidence that cortical alterations represent a core pathophysiological feature of major depressive disorder (MDD). Differential contributions of cortical features of neurodevelopmental origin, which may distinctly contribute to MDD vulnerability, disease-onset, or symptom expression, are unclear at present. METHODS We investigated distinct markers of cortical neurodevelopment, i.e. local cortical gyrification (LGI) and thickness (CT) in patients with MDD (n = 38) and healthy controls (HC, n = 22) using 3 T structural magnetic resonance imaging data and surface-based data analysis techniques. CT and LGI were computed using the Computational Anatomy Toolbox (CAT12). Analyses were performed for the entire cortical surface followed by a complementary regions-of-interest approach. RESULTS MDD patients showed significantly greater LGI in frontal, cingulate, parietal, temporal, and occipital regions compared to HC (FDR-corrected at p < 0.05 using threshold-free cluster enhancement). No significant differences of CT were found. In the MDD-group, correlations were found between duration of illness in years and number of depressive episodes and LGI of frontal, temporal, and parietal regions (p < 0.05). LIMITATIONS Main limitations are the relatively modest sample size and a cross-sectional study design. We did not control for early environmental factors potentially influencing neurodevelopment, such as childhood trauma. We report associations uncorrected for multiple comparisons. CONCLUSIONS The data suggest different local trajectories of cortical change in MDD. In addition, our data support the notion that aberrant cortical development may serve as a vulnerability marker of MDD, as well as a potential predictor of disease course.

Common and distinct patterns of abnormal cortical gyrification in major depression and borderline personality disorder

Abnormal gray matter volume has been consistently reported in patients with major depressive disorder (MDD), but markers of cortical neurodevelopment have been rarely investigated. Also, it is unclear whether there exist common versus distinct spatial patterns of abnormal cortical development across different disorders presenting with negative emotions and deficient affective regulation. In this study, we used structural MRI at 3T to investigate the local gyrification index (LGI), a marker of fetal/infant neurodevelopment, in adult female patients with MDD (n = 22), in adult female patients with borderline personality disorder (BPD) (n = 17), and in controls (n = 22). Reduced cortical folding of the precuneus, the superior parietal gyrus and the parahippocampal gyrus was found in both MDD and BPD patients when compared to controls (p < 0.05, cluster-wise probability [CWP] corrected). MDD patients showed additional hypogyrification of the middle frontal gyrus and the fusiform gyrus when compared to both controls and BPD patients (p < 0.05, CWP corrected). In MDD patients, lower LGI of prefrontal regions was significantly associated with the age of disease onset and with the number of depressive episodes. In BPD patients, lower LGI of orbitofrontal regions was associated with impulsivity. Our findings suggest abnormal early cortical development in MDD, affecting brain regions that have been frequently implied in MDD pathophysiology. However, LGI abnormalities may not be specific for MDD, since MDD and BPD patients also exhibited common patterns of hypogyrification. Hypogyrification of cortical regions associated with higher-order cognition appears to be most pronounced in MDD. Abnormal early cortical neurodevelopment may mediate vulnerability to disorders of emotion.