Functional connectome differences in individuals with hallucinations across the psychosis continuum

Hallucinations may arise from an imbalance between sensory and higher cognitive brain regions, reflected by alterations in functional connectivity. It is unknown whether hallucinations across the psychosis continuum exhibit similar alterations in functional connectivity, suggesting a common neural mechanism, or whether different mechanisms link to hallucinations across phenotypes. We acquired resting-state functional MRI scans of 483 participants, including 40 non-clinical individuals with hallucinations, 99 schizophrenia patients with hallucinations, 74 bipolar-I disorder patients with hallucinations, 42 bipolar-I disorder patients without hallucinations, and 228 healthy controls. The weighted connectivity matrices were compared using network-based statistics. Non-clinical individuals with hallucinations and schizophrenia patients with hallucinations exhibited increased connectivity, mainly among fronto-temporal and fronto-insula/cingulate areas compared to controls (P < 0.001 adjusted). Differential effects were observed for bipolar-I disorder patients with hallucinations versus controls, mainly characterized by decreased connectivity between fronto-temporal and fronto-striatal areas (P = 0.012 adjusted). No connectivity alterations were found between bipolar-I disorder patients without hallucinations and controls. Our results support the notion that hallucinations in non-clinical individuals and schizophrenia patients are related to altered interactions between sensory and higher-order cognitive brain regions. However, a different dysconnectivity pattern was observed for bipolar-I disorder patients with hallucinations, which implies a different neural mechanism across the psychosis continuum.publishedVersio

A transdiagnostic comparison of hallucinations

Hallucinations present in a wide range of clinical disorders, including psychiatric, neurological and other medical disorders. Hallucinations also occur in a minority of the general population. As hallucinations are not unique to one disorder, there has been growing consensus that hallucinations should be investigated using a broader transdiagnostic approach. Transdiagnostic research is currently hindered due to the lack of a suitable measurement tool. In part I of the thesis, a new transdiagnostic questionnaire - the Questionnaire for Psychotic experiences (QPE) - was developed. The QPE enables assessment of severity, frequency and phenomenology of psychotic experiences across disorders. The results showed that participants with various disorders reported hallucinations, which confirms that hallucinations should be considered a transdiagnostic phenomenon. A comparison of hallucinations across disorders confirmed previous findings that similar phenomenological characteristics can exist between disorders, and that phenomenological characteristics can differ within a diagnosis. This suggests the existence of subtypes of hallucinations that transcend diagnosis.In part II of the thesis, the neural mechanism of hallucinations was investigated across participants with a schizophrenia-spectrum disorder, bipolar disorder and non-clinical individuals. Previous studies report similar phenomenological characteristics of hallucinations across these participants, suggesting a similar underlying neural mechanism. Our results do not support this hypothesis. Non-clinical individuals and schizophrenia patients with hallucinations show similar alterations of the functional connectome, whereas differential alterations were reported for bipolar disorder patients with hallucinations. This suggests a different underlying neural mechanism for hallucinations in bipolar disorder as compared to non-clinical individuals and patients with schizophrenia