148 research outputs found

    Brain-wide functional inter-hemispheric disconnection is a potential biomarker for schizophrenia and distinguishes it from depression

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    Schizophrenia is associated with disconnectivity in the brain although it is still unclear whether changes within or between hemispheres are of greatest importance. In this paper, an analysis of 152 schizophrenia patients compared with 122 healthy controls was carried out. Comparisons were also made with 39 depression patients and 37 controls to examine whether brain-wide changes in inter- or intra-hemispheric functional connectivity are most associated with the disorder and can distinguish it from depression. The authors developed new techniques (first and second order symmetry) to investigate brain-wide changes in patients (45 regions per hemisphere) and their association with illness duration and symptom severity. Functional connectivity between the same regions in left- and right-hemispheres (first order symmetry) was significantly reduced as was that between the same pairs of regions in the left- and right-hemispheres (second order symmetry) or using all possible inter-hemispheric connections in schizophrenia patients. By contrast, no significant changes were found for brain-wide intra-hemispheric links. First order symmetry changes correlated significantly with positive and negative symptom severity for functional connections linked via the anterior commissure and negative symptoms for those linked via the corpus callosum. Support vector machine analysis revealed that inter-hemispheric symmetry changes had 73–81% accuracy in discriminating schizophrenia patients and either healthy controls or depressed patients. In conclusion, reduced brain-wide inter-hemispheric functional connectivity occurs in schizophrenia, is associated with symptom severity, and can discriminate schizophrenia patients from depressed ones or healthy controls. Brain-wide changes in inter-hemispheric connections may therefore provide a useful potential biomarker for schizophrenia

    The association of psychotic disorders, dopaminergic agents and resting-state EEG/MEG functional connectivity

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    Psychotic disorders are complex and heterogeneous mental disorders with low recovery rates despite a great amount of research on the topic. Various hypotheses exist as to the etiology of psychotic disorders. Amongst these, the dopamine hypothesis and the dysconnectivity hypothesis have been the most enduring in the last six decades. Little is known on how the dopamine and the dysconnectivity hypothesis are associated. The overarching research question of this thesis is to investigate this knowledge gap. Resting-state magneto- and electroencephalography (MEG, EEG) were chosen as non-invasive measurement modalities of dysconnectivity at the source and sensor level of the brain in publication 1. Parameters of resting-state EEG microstate classes A-D were used as a global analysis method of functional connectivity at the sensor level of the brain in publications 2 and 3. The first research question focused on finding systematic evidence on the association of the two hypotheses and was addressed by means of a systematic review (publication 1) of 20 studies published since 2000. Based on the review, no definite conclusion on the association of antipsychotic medication (that mainly acts on the dopamine system) and source- and sensor-level EEG/MEG functional connectivity could be drawn. The second research question focused on whether differences in parameters of resting-state EEG microstate classes A-D are associated to antipsychotic medication. It was addressed by a study (publication 2) that compared 19-channel clinical EEG recordings of medicated (mFEP, n = 17) and medication-naïve (untreated; uFEP, n = 30) patients with first-episode psychotic disorders (FEP). The study results revealed significant decrease of microstate class A and significant increase of microstate class B to differentiate mFEP from uFEP. The third research question focused on whether differences in parameters of resting-state EEG microstate classes A-D are associated with psychosis illness progression and transition to psychosis in FEP and ultra-high-risk (UHR) patients. It was addressed by a study (publication 3) that found significantly increased microstate class A to differentiate a combined group of medication-naïve FEP (n = 29) and UHR patients (n = 54) together from healthy controls (HC, n = 25); significantly decreased microstate class B to differentiate FEP from all UHR patients combined; and significantly decreased microstate class D to differentiate UHR-T patients with (n = 20) from UHR-NT patients without (n = 34) later transition to psychotic disorders using 19-channel EEG recordings. In conclusion across all three publications, an association between the dopamine and the dysconnectivity hypothesis could be demonstrated by means of resting-state EEG microstates assessed in publication 2 and 3. No definite conclusion could be drawn by the systematic review (publication 1). More studies with longitudinal designs are needed to rule-out between-subject differences, track response trajectories, pre-post effects of antipsychotic medication and their association with dysconnectivity. With increased effort, resting-state EEG microstates could contribute to establishing a robust biomarker in a multi- domain approach in order to inform clinicians for the diagnosis, treatment and outcome prediction of psychotic disorders

    Dynamic functional connectivity in schizophrenia and bipolar disorder: A review of the evidence and associations with psychopathological features

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    Alterations of functional network connectivity have been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Recent studies also suggest that the temporal dynamics of functional connec-tivity (dFC) can be altered in these disorders. Here, we summarized the existing literature on dFC in SCZ and BD, and their association with psychopathological and cognitive features. We systematically searched PubMed, Web of Science, and Scopus for studies investigating dFC in SCZ and BD and identified 77 studies. Our findings support a general model of dysconnectivity of dFC in SCZ, whereas a heterogeneous picture arose in BD. Although dFC alterations are more severe and widespread in SCZ compared to BD, dysfunctions of a triple network system underlying goal-directed behavior and sensory-motor networks were present in both disorders. Furthermore, in SCZ, positive and negative symptoms were associated with abnormal dFC.Implications for understanding the pathophysiology of disorders, the role of neurotransmitters, and treatments on dFC are discussed. The lack of standards for dFC metrics, replication studies, and the use of small samples represent major limitations for the field

    Dysconnectivity of the medio-dorsal thalamic nucleus in drug-naïve first episode schizophrenia: diagnosis-specific or trans-diagnostic effect?

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    Converging lines of evidence implicate the thalamocortical network in schizophrenia. In particular, the onset of the illness is associated with aberrant functional integration between the medio-dorsal thalamic nucleus (MDN) and widespread prefrontal, temporal and parietal cortical regions. Because the thalamus is also implicated in other psychiatric illnesses including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), the diagnostic specificity of these alterations is unclear. Here, we determined whether aberrant functional integration between the MDN and the cortex is a specific feature of schizophrenia or a trans-diagnostic feature of psychiatric illness. Effective connectivity (EC) between the MDN and rest of the cortex was measured by applying psychophysiological interaction analysis to resting-state functional magnetic resonance imaging data of 50 patients with first episode schizophrenia (FES), 50 patients with MDD, 50 patients with PTSD and 122 healthy controls. All participants were medication-naïve. The only significant schizophrenia-specific effect was increased EC between the right MDN and the right pallidum (p < 0.05 corrected). In contrast, there were a number of significant trans-diagnostic alterations, with both right and left MDN displaying trans-diagnostic increased EC with several prefrontal and parietal regions bilaterally (p < 0.05 corrected). EC alterations between the MDN and the cortex are not specific to schizophrenia but are a trans-diagnostic feature of psychiatric disorders, consistent with emerging conceptualizations of mental illness based on a single general psychopathology factor. Therefore, dysconnectivity of the MDN could potentially be used to assess the presence of general psychopathology above and beyond traditional diagnostic boundaries

    Sex Differences in the Corpus Callosum in Schizophrenia: A Combined MRI and DTI Study

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    Master'sMASTER OF SOCIAL SCIENCE

    Investigating the link between drug-naive first episode psychoses (FEPs), weight gain abnormalities and brain structural damages: Relevance and implications for therapy

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    Evidence suggests that obesity and overweight may be associated with severe brain structural abnormalities and poor cognitive and functional outcomes in the general population. Despite these observations and the high prevalence of weight gain abnormalities in patients with psychosis spectrum disorders (PSDs), no studies have investigated the impact that these metabolic disturbances may have on brain structures and development in the earliest stages of PSDs. In the present review we shed light on the association between weight gain and brain structural abnormalities that may affect the course of illness in drug-naïve FEPs. Given the lack of studies directly investigating this issue, we firstly identified and critically evaluated the literature assessing weight gain abnormalities and gray or white matter (GM, WM) volumes (either globally or in specific regions of interest) in otherwise healthy obese/overweight adolescents and young adults. We then compared the results of this systematic review with those of two recent meta-analysis investigating GM and WM abnormalities in drug-naïve FEPs. Weight gain in otherwise healthy subjects was consistently associated with frontal and temporal GM atrophy and with reduced integrity of WM in the corpus callosum. Of relevance, all these brain regions are affected in drug-naïve FEPs, and their integrity is associated with clinical, cognitive and functional outcomes. The underlying mechanisms that may explain the association between weight gain, adiposity, and brain damage in both healthy subjects and drug-naïve FEPs are widely discussed. On the basis of this knowledge, we tried: a) to deduce an integrative model for the development of obesity in psychosis spectrum disorders; b) to identify the key vulnerability factors underlying the association between weight gain and psychosis; c) to provide information on new potential targets of intervention

    Stay connected:a family-based diffusion imaging study in psychotic disorder

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    Changes in the way different regions of the brain communicate with one another is considered to be one of the causes of psychotic disorder. White matter anomalies throughout the brain have been found in patients with psychotic disorder. These anomalies are not found in the brains of the patients' healthy siblings and likely reflects disease-related brain pathology. Over a period of roughly three years, a stabilisation of these white matter anomalies was found in the brains of patients compared to an increase in white matter anomalies in those of healthy siblings. Finally, a link was found between increased white matter deterioration in patients with psychotic disorder and greater exposure to cannabis and youth trauma. Prevention campaigns should focus more attention on the harmful effects of environmental stressors that can increase the risk for developing a psychotic disorder
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