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Relational memory, or the ability to form contextual associations among items encountered closely in time, is impaired in schizophrenia. The ability to bind items into a relational memory is dependent on the hippocampus, a region that is abnormal in schizophrenia. However, the hippocampus is also involved in exploratory behavior, leaving open the question whether relational memory deficits in schizophrenia are due to failure of relational binding or diminished visual exploration of individual items during encoding. We studied visual exploration patterns during the encoding of face-scene pairs in 66 healthy control subjects and 69 early psychosis patients, to test the hypothesis that differences in visual exploration during the encoding phase can explain task accuracy differences between the two groups. Psychosis patients had lower explicit test accuracy and were less likely to transition from mouth to eyes during encoding. The visual exploration pattern differences between groups did not mediate the relationship between group and explicit test accuracy. We conclude that early psychosis patients have an abnormal pattern of binding items together during encoding that warrants further research.
Copyright © 2020 Elsevier B.V. All rights reserved.
BACKGROUND - Learning and memory are impaired in schizophrenia. Some theories have proposed that one form of memory, habituation, is particularly impaired. Preliminary evidence suggests that memory impairment is associated with failed hippocampal habituation in patients with chronic schizophrenia. We studied how abnormal habituation of the hippocampus is related to relational memory deficits in the early stage of psychosis.
METHODS - We measured hippocampal activity in 62 patients with early psychosis and 70 healthy individuals using functional magnetic resonance imaging. Habituation was defined as the slope of functional magnetic resonance imaging signal change to repeated presentations of faces and objects. Relational memory ability was measured as the slope of preferential viewing during a face-scene pair eye movement task outside the scanner.
RESULTS - Patients with early psychosis showed impaired relational memory (p < .001) and less hippocampal habituation to objects (p = .01) than healthy control subjects. In the healthy control group, better relational memory was associated with faster anterior hippocampal habituation (faces, r = -.28, p = .03). In contrast, patients with early psychosis showed no brain-behavior relationship (r = .12, p = .40).
CONCLUSIONS - We found evidence for disrupted hippocampal habituation in the early stage of psychosis along with an altered association between hippocampal habituation and relational memory ability. These results suggest that neural habituation may provide a novel target for early cognitive interventions in psychosis.
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Humans constantly take in vast amounts of information, which must be filtered, flexibly manipulated, and integrated into cohesive relational memories in order to choose relevant behaviors. Relational memory is impaired in chronic schizophrenia, which has been linked to hippocampal dysfunction. It is unclear whether relational memory is impaired in the early stage of psychosis.
METHODS - We studied eye movements during a face-scene pairs task as an indirect measure of relational memory in 89 patients in the early stage of psychosis and 84 healthy control participants. During testing, scenes were overlaid with three equally-familiar faces and participants were asked to recall the matching (i.e. previously-paired) face. During Match trials, one face had been previously paired with the scene. During Non-Match trials, no faces matched the scene. Forced-choice explicit recognition was recorded as a direct measure of relational memory.
RESULTS - Healthy control subjects rapidly (within 250-500 ms) showed preferential viewing of the matching face during Match trials. In contrast, preferential viewing was delayed in patients in the early stage of psychosis. Explicit recognition of the matching face was also impaired in the patient group.
CONCLUSIONS - This study provides novel evidence for a relational memory deficit in the early stage of psychosis. Patients showed deficits in both explicit recognition as well as abnormal eye-movement patterns during memory recall. Eye movements provide a promising avenue for the study of relational memory in psychosis, as they allow for the assessment of rapid, nonverbal memory processes.
Copyright © 2019 Elsevier B.V. All rights reserved.
BACKGROUND - The striatum is abnormal in schizophrenia and possibly represents a common neurobiological mechanism underlying psychotic disorders. Resting-state functional magnetic resonance imaging studies have not reached a consensus regarding striatal dysconnectivity in schizophrenia, although these studies generally find impaired frontoparietal and salience network connectivity. The goal of the current study was to clarify the pattern of corticostriatal connectivity, including whether corticostriatal dysconnectivity is transdiagnostic and extends into psychotic bipolar disorder.
METHODS - We examined corticostriatal functional connectivity in 60 healthy subjects and 117 individuals with psychosis, including 77 with a schizophrenia spectrum illness and 40 with psychotic bipolar disorder. We conducted a cortical seed-based region-of-interest analysis with follow-up voxelwise analysis for any significant results. Further, a striatum seed-based analysis was conducted to examine group differences in connectivity between the striatum and the whole cortex.
RESULTS - Cortical region-of-interest analysis indicated that overall connectivity of the salience network with the striatum was reduced in psychotic disorders, which follow-up voxelwise analysis localized to the left putamen. Striatum seed-based analyses showed reduced ventral rostral putamen connectivity with the salience network portion of the medial prefrontal cortex in both schizophrenia and psychotic bipolar disorder.
CONCLUSIONS - The current study found evidence of transdiagnostic corticostriatal dysconnectivity in both schizophrenia and psychotic bipolar disorder, including reduced salience network connectivity, as well as reduced connectivity between the putamen and the medial prefrontal cortex. Overall, the current study points to the relative importance of salience network hypoconnectivity in psychotic disorders.
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Neuropsychological impairment is common in schizophrenia and psychotic bipolar disorder. It has been hypothesized that the pathways leading to impairment differ between disorders. Cognitive impairment in schizophrenia is believed to result largely from atypical neurodevelopment, whereas bipolar disorder is increasingly conceptualized as a neuroprogressive disorder. The current investigation tested several key predictions of this hypothesis.
METHODS - Current neuropsychological functioning and estimated premorbid intellectual ability were assessed in healthy individuals (n = 260) and a large, cross-sectional sample of individuals in the early and chronic stages of psychosis (n = 410). We tested the following hypotheses: 1) cognitive impairment is more severe in schizophrenia in the early stage of psychosis; and 2) cognitive decline between early and chronic stages is relatively greater in psychotic bipolar disorder. Additionally, individuals with psychosis were classified as neuropsychologically normal, deteriorated, and compromised (i.e. below average intellectual functioning) to determine if the frequencies of neuropsychologically compromised and deteriorated patients were higher in schizophrenia and psychotic bipolar disorder, respectively.
RESULTS - Neuropsychological impairment in the early stage of psychosis was more severe in schizophrenia. Psychotic bipolar disorder was not associated with relatively greater cognitive decline between illness stages. The frequency of neuropsychologically compromised patients was higher in schizophrenia; however, substantial portions of both schizophrenia and psychotic bipolar disorder patients were classified as neuropsychologically compromised and deteriorated.
CONCLUSIONS - While schizophrenia is associated with relatively greater neurodevelopmental involvement, psychotic bipolar disorder and schizophrenia cannot be strictly dichotomized into purely neuroprogressive and neurodevelopmental illness trajectories; there is evidence of both processes in each disorder.
Copyright © 2018 Elsevier B.V. All rights reserved.
BACKGROUND - Across networks, connectivity within the frontoparietal network (FPN) and cingulo-opercular network (CON) exhibits reductions earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems. By leveraging a large sample of patients with psychosis from early to chronic illness stages, this study sought to determine whether the CON and FPN exhibit evidence of accelerated aging in psychotic disorders, confirm associations between network efficiency and cognition, and determine whether reduced network efficiency is observed in early-stage psychosis.
METHODS - Resting-state functional magnetic resonance imaging and cognitive data were obtained on 240 patients with psychotic disorder and 178 healthy control participants (HCs). Global efficiency, a measure of functional integration, was calculated for the CON, FPN, subcortical network, and visual network. Associations with age and cognition were assessed and compared between groups.
RESULTS - Consistent with accelerated aging, significant group by age interactions reflected significantly stronger relationships between efficiency and age in patients with psychosis than in HCs for both the CON (psychosis: r = -.37; HC: r = -.16) and FPN (psychosis: r = -.31; HC: r = -.05). Accelerated aging was not observed in either the subcortical or visual network, suggesting specificity for cognitive networks that decline earliest in healthy aging. Replicating prior findings, efficiency of both the CON and FPN correlated with cognitive function across all participants (rs > .11, ps < .031). Furthermore, patients with chronic psychosis (p = .004), but not patients with early psychosis (p = .553), exhibited significantly lower FPN efficiency compared with HCs.
CONCLUSIONS - Functional integration of higher-order cognitive networks is intact in early psychosis but exhibits evidence of accelerated aging, suggesting the potential for intervention targeting cognition within the early psychosis period.
Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Previous studies in psychosis patients have shown hippocampal volume deficits across anterior and posterior regions or across subfields, but subfield specific changes in volume along the hippocampal long axis have not been examined. Here, we tested the hypothesis that volume changes exist across the hippocampus in chronic psychosis but only the anterior CA region is affected in early psychosis patients. We analyzed structural MRI data from 179 patients with a non-affective psychotic disorder (94 chronic psychosis; 85 early psychosis) and 167 heathy individuals demographically matched to the chronic and early psychosis samples respectively (82 matched to chronic patients; 85 matched to early patients). We measured hippocampal volumes using Freesurfer 6-derived automated segmentation of both anterior and posterior regions and the CA, dentate gyrus, and subiculum subfields. We found a hippocampal volume deficit in both anterior and posterior regions in chronic psychosis, but this deficit was limited to the anterior hippocampus in early psychosis patients. This volume change was more pronounced in the anterior CA subfield of early psychosis patients than in the dentate gyrus or subiculum. Our findings support existing models of psychosis implicating initial CA dysfunction with later progression to other hippocampal regions and suggest that the anterior hippocampus may be an important target for early interventions.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Relational memory is impaired in chronic schizophrenia. It is unclear if similar deficits are already present in the early stage of psychosis. We used the Associative Inference Paradigm to test relational memory ability in the early stage of a non-affective psychotic disorder. Eighty-two early stage psychosis patients and 67 healthy control subjects were trained on 3 sets of 30 paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), F3-F4 (two new faces). Subjects who reached 80% recall accuracy of the paired associates during training were then tested for their ability to recall the previously seen pairs and solve a novel, inferential pairing F1-F2 (faces linked through association to same house). Sixty early psychosis patients (73%) and 67 healthy control subjects (100%) successfully reached the accuracy threshold (80%) during training and were included in the analysis of relational memory. The early stage psychosis patients showed less of an associative inference effect than the healthy controls (pair type by group interaction: F (1,125) = 5.04, p < 0.05). However, the majority of early psychosis patients (52%) displayed intact inferential memory, compared to our prior study which revealed just 16% of chronic schizophrenia patients had intact inferential memory. Patients in the early stage of psychosis show a relational memory deficit, although less pronounced than in chronic schizophrenia. Longitudinal studies are needed to examine the progression of relational memory deficits in schizophrenia and its associations with clinical, functional, and biological measures.
Copyright © 2018 Elsevier B.V. All rights reserved.
The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.
Tract-based spatial statistics (TBSS) has proven to be a popular technique for performing voxel-wise statistical analysis that aims to improve sensitivity and interpretability of analysis of multi-subject diffusion imaging studies in white matter. With the advent of advanced diffusion MRI models - e.g., the neurite orientation dispersion density imaging (NODDI), it is of interest to analyze microstructural changes within gray matter (GM). A recent study has proposed using NODDI in gray matter based spatial statistics (N-GBSS) to perform voxel-wise statistical analysis on GM microstructure. N-GBSS adapts TBSS by skeletonizing the GM and projecting diffusion metrics to a cortical ribbon. In this study, we propose an alternate approach, known as gray matter surface based spatial statistics (GS-BSS), to perform statistical analysis using gray matter surfaces by incorporating established methods of registration techniques of GM surface segmentation on structural images. Diffusion microstructure features from NODDI and GM surfaces are transferred to standard space. All the surfaces are then projected onto a common GM surface non-linearly using diffeomorphic spectral matching on cortical surfaces. Prior post-mortem studies have shown reduced dendritic length in prefrontal cortex region in schizophrenia and bipolar disorder population. To validate the results, statistical tests are compared between GS-BSS and N-GBSS to study the differences between healthy and psychosis population. Significant results confirming the microstructural changes are presented. GS-BSS results show higher sensitivity to group differences between healthy and psychosis population in previously known regions.