Hippocampus-Centered Network Is Associated With Positive Symptom Alleviation in Patients With First-Episode Psychosis.

BACKGROUND: Previous functional magnetic resonance imaging studies have reported widespread brain functional connectivity alterations in patients with psychosis. These studies have mostly used either resting-state or simple-task paradigms, thereby compromising experimental control or ecological validity, respectively. Additionally, in a conventional functional magnetic resonance imaging intrasubject functional connectivity analysis, it is difficult to identify which connections relate to extrinsic (stimulus-induced) and which connections relate to intrinsic (non-stimulus-related) neural processes. METHODS: To mitigate these limitations, we used intersubject functional connectivity (ISFC) to analyze longitudinal functional magnetic resonance imaging data collected while 36 individuals with first-episode psychosis (FEP) and 29 age- and sex-matched population control participants watched scenes from the fantasy movie Alice in Wonderland at baseline and again at 1-year follow-up. Furthermore, to allow unconfounded comparison and to overcome possible circularity of ISFC, we introduced a novel approach wherein ISFC in both the FEP and population control groups was calculated with respect to an independent group of participants (not included in the analyses). RESULTS: Using this independent-reference ISFC approach, we found an interaction effect wherein the independent-reference ISFC in individuals with FEP, but not in the control group participants, was significantly stronger at baseline than at follow-up in a network centered in the hippocampus and involving thalamic, striatal, and cortical regions, such as the orbitofrontal cortex. Alleviation of positive symptoms, particularly delusions, from baseline to follow-up was correlated with decreased network connectivity in patients with FEP. CONCLUSIONS: These findings link deviation of naturalistic information processing in the hippocampus-centered network to positive symptoms.

Connectivity alterations of mesostriatal pathways in first episode psychosis.

BACKGROUND AND HYPOTHESIS: Pathogenic understanding of the psychotic disorders converges on regulation of dopaminergic signaling in mesostriatocortical pathways. Functional connectivity of the mesostriatal pathways may inform us of the neuronal networks involved. STUDY DESIGN: This longitudinal study of first episode psychosis (FEP) (49 patients, 43 controls) employed seed-based functional connectivity analyses of fMRI data collected during a naturalistic movie stimulus. STUDY RESULTS: We identified hypoconnectivity of the dorsal striatum with the midbrain, associated with antipsychotic medication dose in FEP, in comparison with the healthy control group. The midbrain regions that showed hypoconnectivity with the dorsal striatum also showed hypoconnectivity with cerebellar regions suggested to be involved in regulation of the mesostriatocortical dopaminergic pathways. None of the baseline hypoconnectivity detected was seen at follow-up. CONCLUSIONS: These findings extend earlier resting state findings on mesostriatal connectivity in psychotic disorders and highlight the potential for cerebellar regulation of the mesostriatocortical pathways as a target of treatment trials.

Associations between acceptance of the implausible bias, theory of mind and delusions in first-episode psychosis patients; A longitudinal study.

Multiple different cognitive biases, among them the liberal acceptance (LA) bias, have been suggested to contribute to reality distortion in psychotic disorders. Earlier studies have been cross-sectional and considered a limited set of cognitive correlates of psychosis, thus the relationship between LA bias and psychosis remains poorly known. We studied a similar bias (acceptance of the implausible (AOI)) in 62 first-episode psychosis (FEP) patients and 62 control subjects, who watched movie scenes with varying degrees of realism and were asked to evaluate the probability of these events occurring in real life. We assessed theory of mind (ToM) performance using the Hinting task and delusion severity using Brief Psychiatric Rating Scale item 11. We correlated the magnitude of AOI with the severity of delusions and performance in the ToM task. Furthermore, we used 1-year follow-up data from 40 FEP patients and 40 control subjects to disentangle state vs trait-like characteristics of AOI. At baseline FEP patients expressed more AOI than control subjects, and the magnitude of AOI correlated positively with the severity of delusions and negatively with ToM performance. At the one-year follow-up, when most patients were in remission, patients still displayed increased AOI, which no longer correlated with delusions. These findings support the notion that the AOI bias could represent a trait rather than a state feature and support further studies to test the hypothesis that it could be one of the causal factors of psychotic disorders, possibly associated with ToM.

State-like changes in the salience network correlate with delusion severity in first-episode psychosis patients.

BACKGROUND AND HYPOTHESIS: Delusions are characteristic of psychotic disorders; however, the brain correlates of delusions remain poorly known. Imaging studies on delusions typically compare images across individuals. Related confounding of inter-individual differences beyond delusions may be avoided by comparing delusional and non-delusional states within individuals. STUDY DESIGN: We studied correlations of delusions using intra-subject correlation (intra-SC) and inter-subject correlation of functional magnetic resonance imaging (fMRI) signal time series, obtained during a movie stimulus at baseline and follow-up. We included 27 control subjects and 24 first-episode psychosis patients, who were free of delusions at follow-up, to calculate intra-SC between fMRI signals obtained during the two time points. In addition, we studied changes in functional connectivity at baseline and during the one-year follow-up using regions where delusion severity correlated with intra-SC as seeds. RESULTS: The intra-SC correlated negatively with the baseline delusion severity in the bilateral anterior insula. In addition, we observed a subthreshold cluster in the anterior cingulate. These three regions constitute the cortical salience network (SN). Functional connectivity between the bilateral insula and the precuneus was weaker in the patients at baseline than in patients at follow-up or in control subjects at any time point. CONCLUSIONS: The results suggest that intra-SC is a powerful tool to study brain correlates of symptoms and highlight the role of the SN and internetwork dysconnectivity between the SN and the default mode network in delusions.