Connectivity-enhanced diffusion analysis reveals white matter density disruptions in first episode and chronic schizophrenia.

Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 first episode and 27 chronic) and 64 controls. Analysis of FA was combined with "fixel-based" analysis, the latter of which leverages connectivity and crossing-fiber information to assess both fiber bundle density and organizational complexity (i.e., presence and magnitude of off-axis diffusion signal). Compared with controls, patients with schizophrenia displayed clusters of significantly lower FA in the bilateral frontal lobes, right dorsal centrum semiovale, and the left anterior limb of the internal capsule. All FA-based group differences overlapped substantially with regions containing complex fiber architecture. FA within these clusters was positively correlated with principal axis fiber density, but inversely correlated with both secondary/tertiary axis fiber density and voxel-wise fiber complexity. Crossing fiber complexity had the strongest (inverse) association with FA (r = -0.82). When crossing fiber structure was modeled in the MRtrix fixel-based analysis pipeline, patients exhibited significantly lower fiber density compared to controls in the dorsal and posterior corpus callosum (central, postcentral, and forceps major). Findings of lower FA in patients with schizophrenia likely reflect two inversely related signals: reduced density of principal axis fiber tracts and increased off-axis diffusion sources. Whereas the former confirms at least some regions where myelin and or/axon count are lower in schizophrenia, the latter indicates that the FA signal from principal axis fiber coherence is broadly contaminated by macrostructural complexity, and therefore does not necessarily reflect microstructural group differences. These results underline the need to move beyond tensor-based models in favor of acquisition and analysis techniques that can help disambiguate different sources of white matter disruptions associated with schizophrenia

The early longitudinal course of cognitive deficits in schizophrenia.

Cognitive impairment is a core feature of schizophrenia. However, the longitudinal course and pattern of this impairment, and its relationship to functional outcome, are not fully understood. Among the likely factors in the persistence of cognitive deficits in schizophrenia are brain tissue changes over time, which in turn appear to be related to antipsychotic medication adherence. Cognitive deficits are viewed as a core feature of schizophrenia primarily because cognitive deficits clearly exist before the onset of psychosis and can predict illness onset among those at high risk of developing the illness. Additionally, these deficits often persist during symptomatic remissions in patients and are relatively stable across time both in patients and in individuals at risk for schizophrenia. Despite clear evidence that cognitive impairment can predict functional outcome in chronic schizophrenia, results of studies examining this relationship in the early phase of psychosis have been mixed. Recent data, however, strongly suggest that interventions targeting early cognitive deficits may be crucial to the prevention of chronic disability and thus should be a prominent target for therapy. Finally, it is vital to keep schizophrenia patients consistently on their antipsychotic medications. A novel method of examining intracortical myelin volume indicated that the choice of antipsychotic treatment had a differential impact on frontal myelination. These data suggest that long-acting injectable antipsychotic medication may prevent patients from declining further through a combination of better adherence and pharmacokinetics

Family burden predicts functional outcome in the early course of schizophrenia beyond psychiatric symptoms and baseline functioning

The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the individual is able to work or attend school during the first year of treatment. Forty-one participants with a recent first episode of schizophrenia and their families enrolled in two NIMH-funded protocols through the UCLA Aftercare Research Program completed a measure of family burden at baseline. Amount of work during this time was also recorded. Baseline family burden was associated with work status (no work, part-time work, or full-time work) at both the six-month, r = -0.321, p = .04, and one-year time point, r = - 0.47, p = .002. Family burden was also associated with hours participated in work/school hours at the six-month time point, r = -0.390, p = .012, and at the one-year time point, r = -0.492, p = .01. Further exploration into the family burden measure shows that family perceived limited opportunities resulting from the individual's psychiatric disorder was associated with worse functional outcome at all three time points beyond psychiatric symptoms and baseline functioning. Missed opportunities due to a family member's illness may reduce the level of support provided to the individual and thus impact their psychosocial functioning. Our findings suggest that this dimension of family burden is highlighting the importance of and need for more balanced family support to boost functional outcome

Neurocognitive and social cognitive correlates of formal thought disorder in schizophrenia patients

The neurocognitive and social cognitive correlates of two types of formal thought disorder (i.e., bizarre-idiosyncratic and concrete thinking) were examined in 47 stable outpatients with schizophrenia. Both types of thinking disturbance were related to impairments in verbal learning, intrusions in verbal memory, immediate auditory memory, sustained attention, and social schema knowledge. Distractibility during an immediate memory task was associated with more frequent bizarre verbalizations but not concreteness. Impaired verbal learning rate and intrusions in verbal memory independently contributed to the prediction of bizarre responses, whereas intrusions in verbal memory and impaired immediate memory independently contributed to concrete thinking. This pattern of findings is consistent with the view that neurocognitive and, possibly, social cognitive deficits underlie these two aspects of formal thinking disturbance in schizophrenia

Cognitive Assessment Interview (CAI): Validity as a co-primary measure of cognition across phases of schizophrenia

BackgroundProgress has been made in developing interview-based measures for the assessment of cognitive functioning, such as the Cognitive Assessment Interview (CAI), as co-primary measures that compliment objective neurocognitive assessments and daily functioning. However, a few questions remain, including whether the relationships with objective cognitive measures and daily functioning are high enough to justify the CAI as an co-primary measure and whether patient-only assessments are valid.MethodsParticipants were first-episode schizophrenia patients (n=60) and demographically-similar healthy controls (n=35), chronic schizophrenia patients (n=38) and demographically similar healthy controls (n=19). Participants were assessed at baseline with an interview-based measure of cognitive functioning (CAI), a test of objective cognitive functioning, functional capacity, and role functioning at baseline, and in the first episode patients again 6 months later (n=28).ResultsCAI ratings were correlated with objective cognitive functioning, functional capacity, and functional outcomes in first-episode schizophrenia patients at similar magnitudes as in chronic patients. Comparisons of first-episode and chronic patients with healthy controls indicated that the CAI sensitively detected deficits in schizophrenia. The relationship of CAI Patient-Only ratings with objective cognitive functioning, functional capacity, and daily functioning were comparable to CAI Rater scores that included informant information.ConclusionsThese results confirm in an independent sample the relationship of the CAI ratings with objectively measured cognition, functional capacity, and role functioning. Comparison of schizophrenia patients with healthy controls further validates the CAI as an co-primary measure of cognitive deficits. Also, CAI change scores were strongly related to objective cognitive change indicating sensitivity to change

Value-Directed Remembering in First-Episode Schizophrenia

ObjectiveMemory deficits in individuals with schizophrenia are well-established, but less is known about how schizophrenia affects metacognitive processes such as metamemory. We investigated metamemory ability using the value-directed remembering task, which assesses the degree to which participants use value cues to guide their learning of a list of items (i.e., their memory selectivity).MethodParticipants were patients undergoing treatment following a recent first episode of schizophrenia (n = 20) and demographically comparable healthy controls (n = 18). Participants viewed six lists of 24 words where each word was paired with either a low value (1-3 points) or a high value (10-12 points), and they were instructed to maximize their score on free recall tests given after each list. After the final free recall test, participants completed a recognition test where they gave remember/know judgments.ResultsOn tests of free recall, patients showed reduced memory selectivity relative to healthy controls. On the recognition test, patients failed to show an effect of value on recognition of nonrecalled words, in contrast to healthy controls, who showed a significant value effect that was characterized by greater "remember" judgments. Patients initially overestimated their memory capacity but were able to adjust their estimates to be more accurate based on task experience. Patients' self-reports of memory selectivity were unrelated to their actual memory selectivity.ConclusionsPatients with first-episode schizophrenia had substantial impairments on the value-directed remembering task, but areas of preserved metamemory ability were also observed. These findings have potential implications for cognitive training interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Temporal lobe thickness and verbal memory in first-degree relatives of individuals with schizophrenia.

Cortical thinning in frontal and temporal regions has been reported in individuals diagnosed with schizophrenia and, less consistently, among their unaffected first-degree relatives. Likewise, first-degree relatives demonstrate attenuated differences in neurocognitive performance relative to healthy controls, indicating that neurocognitive performance may be an important endophenotype of the disorder. Less is known about how cortical thickness relates to neurocognitive performance in these individuals. Given the robust nature of temporal structural abnormalities in schizophrenia, this study aimed to identify how temporal lobe cortical thickness might relate to verbal memory in first-degree relatives. Unaffected parents and siblings of individuals with adult-onset schizophrenia (N=62) and individuals in healthy control families (N=70) participating in the UCLA Family Study received a structural MRI and completed a battery of neurocognitive tests. Cortical thickness was estimated across the cortex and thickness measures of all regions in the temporal lobe were summed, averaged, and residualized for age and sex to produce a variable. A verbal learning factor was derived from two common tests of verbal learning and memory, the CVLT-II and Logical Memory of the WMS-III. Results demonstrated a significant interaction between group and verbal learning in relationship to temporal lobe thickness. Post-hoc analyses revealed significant correlations between verbal learning and cortical thickness in the relatives of schizophrenia patients which were driven by immediate recall scores on the CVLT-II and Logical Memory. These findings indicate that cortical thickness in the temporal cortex may represent a structural correlate for encoding verbal information in unaffected relatives of individuals with schizophrenia