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Item does not contain fulltext, In line with the Research Domain Criteria (RDoC), we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis, to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans, for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress, was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus and thalamus across the different modalities of this component, may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems and sensitivity to sensory stimuli respectively. Taken together, the findings from our extentensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.

Contains fulltext : 295436.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Background: It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). Objective: The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. Methods: This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged >= 18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. Results: We

Item does not contain fulltext, Background: It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). Objective: The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. Methods: This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged >= 18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. Results: We

Contains fulltext : 252781.pdf (Publisher’s version ) (Open Access), Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders.

Contains fulltext : 284920.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum-a central hub in motor, cognitive, affective and reward-related brain circuits-and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

Item does not contain fulltext, Self-referent negative memory bias is a known risk factor for depression, but recent evidence suggests its function as a transdiagnostic cognitive depressotypic marker. The amygdala's sensitivity for negative information is considered a neurobiological depressotypic marker. However, their relationship remains unknown. We transdiagnostically investigated the association between the amygdala's sensitivity, self-referent negative memory bias and its two components: negative endorsement bias and negative recall bias. Patients (n= 125) with (multimorbid) stress-related and neurodevelopmental psychiatric disorders and healthy controls (n= 78) performed an fMRI task to assess the amygdala's sensitivity for negative information and a task outside the scanner for the biases. Linear regression models assessed their associations. The left amygdala's sensitivity for negative information was significantly positively associated with negative recall bias in patients, but not controls. There were no significant associations with self-referent negative memory bias or negative endorsement bias or between the two depressotypic markers. Thus, the left amygdala's sensitivity for negative information may be considered a neural marker of negative memory bias across psychiatric diagnoses. Further research on the interactons with known determinants such as genetic predisposition is required to fully understand the relationship between the amygdala's sensitivity for negative information and these biases.

Radboud University, 09 november 2021, Promotores : Tendolkar, I., Schene, A.H., Fernandez, G.S.E. Co-promotor : Eijndhoven, P.F.P. van, Contains fulltext : 238969.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear. METHODS: We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms. RESULTS: We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. LIMITATIONS: The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings. CONCLUSION: Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

Contains fulltext : 241396.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 217482.pdf (publisher's version ) (Open Access), Clinically, it is well-established that vulnerability to stress is a common feature across a broad spectrum of psychiatric disorders. However, this link has been mechanistically studied almost exclusively in patients with so-called stress-related disorders such as depression and anxiety. To probe transdiagnostic mechanisms, we set out to study the acute stress response across a broader range of psychiatric disorders taking a large-scale brain network perspective. We investigated the brain's response to a mild, experimentally well-controlled psychological stressor in the form of an aversive movie. We studied 168 patients with stress-related and/or neurodevelopmental disorders (including comorbidity) and 46 control subjects. We focused on three networks that have a central role in the brain's stress response and are affected in a wide range of psychiatric disorders: the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). Our results support an increased vulnerability to stress across all patients, indicated by a higher subjective stress level at baseline and follow-up compared to matched controls. At the brain systems level, the stress response was characterized by a relatively decreased FPN connectivity and an absence of a decrease in the within DMN connectivity across all disorders compared to controls. At the neurocognitive level, these findings may reflect a diminished top-down control and a tendency to more pronounced (negative) self-referential processing. Besides these shared aspects of the maladaptive stress response, we also discuss indications for disorder-specific aspects. Taken together, our results emphasize the importance of investigating the mechanistic underpinnings of psychiatric disorders transdiagnostically as recently done in neurogenetics.

Radboud University, 14 oktober 2019, Promotores : Watt, J.G. van der, Oort, J. van, Contains fulltext : 208287.pdf (publisher's version ) (Open Access)