Schizophrenia Research-Cognition最新文献

With an unmet clinical need for effective interventions for cognitive and negative symptoms in patients with schizophrenia, measures of functional status (often a co-primary endpoint) remain key clinical trial outcomes. This review aims to give an overview of the different types of functional assessments commonly used in clinical trials and research involving patients with schizophrenia and highlight pertinent challenges surrounding the use of these as reliable, sensitive, and specific assessments in intervention trials. We provide examples of commonly used functional measures and highlight emerging real-time digital assessment tools. Informant- and clinician-rated functional outcome measures and functional capacity assessments are valid, commonly used measures of functional status that try to overcome the need for often overly ambitious and insensitive ‘real world’ milestones. The wide range of scientific and practical challenges associated with these different tools leave room for the development of improved functional outcome measures for use in clinical trials. In particular, many existing measures fail to capture small, but meaningful, functional changes that may occur over the course of typically short intervention trials. Adding passive digital data collection and short active real-time digital assessments whilst patients go about their day offers the opportunity to build a more fine-grained picture of functional improvements that, if thoughtfully developed and carefully applied, could provide the sensitivity needed to accurately evaluate functional status in intervention studies, aiding the development of desperately needed treatments.

Cognitive Remediation Therapy (CRT) represents the gold standard treatment for cognitive impairment in schizophrenia, but the permanence of its effects over time have been poorly investigated. Our study aims to evaluate long lasting cognitive and functional effects of CRT together with standard rehabilitation interventions (SRT) in a group of patients diagnosed with schizophrenia, 10 years after the end of the treatment. Forty patients, previously included in a 5-year follow-up study evaluating the effects of CRT combined with SRT, were revalued 10 years after the complete of the intervention. Results revealed that cognitive and functional improvements of combined CRT/SRT interventions are still preserved 10 years after the end of the treatments, with the only exception of psychomotor speed and coordination cognitive subdomain. Moreover, investigating persistence of the influence of SRT, patients that underwent a shorter SRT following CRT (six months vs one year) showed worsened processing speed abilities.

This is the first study confirming that cognitive and functional improvements of joint CRT/SRT interventions are still conserved 10 years after the end of the treatments. Preliminary datas suggest that a longer SRT following CRT may lead to significant benefits, in terms of cognitive gains, in patients affected by schizophrenia.

Background

Emotion recognition deficits are linked with social dysfunction in psychosis, as is inaccurate self-assessment of emotion recognition abilities. However, little is known about the link between ER and real-time social appraisals and behavior.

Methods

In 136 people with psychotic disorders or affective disorder with psychosis we administered a novel ecological momentary cognitive test of emotion recognition which both assesses emotion recognition ability and self-assessed performance in conjunction with ecological momentary assessment of social appraisals, motivation, and time spent alone. Hybrid mixed effects models evaluated emotion recognition's associations with social experiences.

Results

Better recognition ability was associated with greater pleasure and more positive appraisals of others during interactions, whereas accuracy of self-assessment of emotion recognition ability was associated with more positive appraisals of interactions and social motivation. Overestimation of emotion recognition was linked with concurrent higher social motivation yet greater desire to avoid others. Time alone was unrelated to emotion recognition ability or self-assessment of ability.

Discussion

Mobile emotion recognition performance was associated with appraisals of recent interactions but not behavior. Self-assessment of social cognitive performance was associated with more positive appraisals and social motivation, and may be a novel target for interventions aimed at social dysfunction.

Background

Paranoid ideation is a core feature of psychosis and is associated with impaired social functioning. Severity of paranoia can fluctuate across time as symptoms wax and wane; however, no study has systematically investigated how this intra-individual variability in paranoia may relate to social impairments and social functioning.

Methods

Fifty-five patients with DSM-5 diagnoses and recent paranoia were followed for up to one year and completed the suspiciousness/persecution section (P6) of the Positive and Negative Symptom Scale (PANSS) on a monthly basis to monitor fluctuations in paranoia. Categorical changes between paranoid and non-paranoid status were monitored and tallied. Participants self-reported current paranoia and anxiety levels as well as social functioning when demonstrating paranoia changes.

Results

Most patients showed changes between paranoid categories (60%). Individuals with no paranoia change showed higher current paranoia and lower independence-competence subscores of the Birchwood Social Functioning Scale (SFS) compared with those with one change. Current paranoia and state anxiety explained significant variance in the prosocial activities subscore of SFS, and importantly, paranoia changes accounted for variance above and beyond these effects. Individuals with higher current paranoia participated less in prosocial activities, however those with higher paranoia variability were more involved in social activities. Similarly, individuals with more paranoia variability demonstrated better overall social functioning as measured by the averaged SFS total score.

Conclusion

Paranoia fluctuation is prevalent across time, and both paranoia severity and variability impact social functioning, in that lower levels of paranoia severity and higher levels of paranoia variability are associated with better interpersonal functioning.

We have previously shown that schizophrenia (SCZ) participants with high community functioning demonstrate better verbal working memory (vWM) performance relative to those with low community functioning. In the present study, we investigated whether neuroanatomical differences in regions supporting vWM also exist between schizophrenia groups that vary on community functioning. Utilizing magnetic resonance imaging, shape features of deep-brain nuclei known to be involved in vWM were calculated in samples of high functioning (HF-SCZ, n = 23) and low functioning schizophrenia participants (LF-SCZ, n = 18), as well as in a group of healthy control participants (CON, n = 45). Large deformation diffeomorphic metric mapping was employed to characterize surface anatomy of the caudate nucleus, globus pallidus, hippocampus, and thalamus. Statistical analyses involved linear mixed-effects models and vertex-wise contrast mapping to assess between-group differences in structural shape features, and Pearson correlations to evaluate relationships between shape metrics and vWM performance. We found significant between-group main effects in deep-brain surface anatomy across all structures. Post-hoc comparisons revealed HF-SCZ and LF-SCZ groups significantly differed on both caudate and hippocampal shape, however, significant correlations with vWM were only observed in hippocampal shape for both SCZ groups. Specifically, more abnormal hippocampal deformation was associated with lower vWM suggesting hippocampal shape is both a neural substrate for vWM deficits and a potential biomarker to predict or monitor the efficacy of cognitive rehabilitation. These findings add to a growing body of literature related to functional outcomes in schizophrenia by demonstrating unique shape patterns across the spectrum of community functioning in SCZ.

Cognitive impairment in schizophrenia represents one of the main obstacles to clinical and functional recovery. This expert group paper brings together experts in schizophrenia treatment to discuss scientific progress in the domain of cognitive impairment to address cognitive impairments and their consequences in the most effective way. We report on the onset and course of cognitive deficits, linking them to the alterations in brain function and structure in schizophrenia and discussing their role in predicting the transition to psychosis in people at risk. We then address the assessment tools with reference to functioning and social cognition, examining the role of subjective measures and addressing new methods for measuring functional outcomes including technology based approaches. Finally, we briefly review treatment options for cognitive deficits, focusing on cognitive remediation programs, highlighting their effects on brain activity and conclude with the potential benefit of individualized integrated interventions combing cognitive remediation with other approaches.

Although there is substantial evidence of the association between cognitive impairment and work in people with severe mental illnesses (SMI) in developed countries, less is known about this relationship in developing countries such as India. Studies showing higher rates of employment in people with SMI in developing countries than developed ones raise the question of whether cognitive functioning is related to work status and characteristics of work (e.g., wages earned). We conducted a one-year follow-up study to investigate the relationship between employment and cognitive functioning, assessed with the Montreal Cognitive Assessment (MoCA), in 150 participants with SMI (92% schizophrenia) living in an urban area and receiving psychiatric outpatient treatment at a public hospital in India. The MoCA had good internal reliability and test-retest reliability over the one-year period. Better cognitive functioning was associated with younger age, shorter duration of illness, higher education, and male gender. Both younger and older participants with higher cognitive functioning at baseline were more likely to be employed at baseline and one year later. Work status at baseline and one year follow-up was consistently related to executive functions among younger participants, and to attention among older participants, suggesting changes over the course of illness in the importance of specific cognitive domains for achieving satisfactory work performance. The findings suggest that cognitive functioning is associated with employment in people with SMI in India. Attention to impaired cognitive functioning may be critical to improving employment outcomes in this population.

Disturbances in self-monitoring are core symptoms of schizophrenia. Some research suggests an over-reliance on exteroceptive cues and a reduced weighting of self-generated interoceptive signals to guide perception. The vestibular sense provides important self-generated information about the body in space. Alterations of vestibular function are reported in schizophrenia, but it is unknown whether internally generated vestibular information is discounted in favour of exteroceptive input. In this study, we test for evidence of an over-reliance on exteroceptive visual cues and a reduced weighting of vestibular signals in guiding perception. In a group of individuals with schizophrenia and healthy controls, we used a well-studied visual illusion – the Tilt Illusion – to probe the respective weight given to visual and vestibular cues in judging line orientation. The Tilt Illusion reveals that perceived orientation of a vertical grating is biased by the orientation in its surround. This illusion increases when the head is tilted, due to the reduced reliability of vestibular information that would otherwise provide an internally generated reference for vertical. We predicted that an over-reliance on exteroceptive cues in schizophrenia would lead to a reduced susceptibility to the effects of head position on Tilt Illusion strength. We find no difference between patients and controls. Both groups show comparable Tilt Illusion magnitudes that increase when the head is tilted. Thus, our findings suggest that chronic patients with schizophrenia adequately combine self-generated vestibular cues and exteroceptive visual input to judge line verticality. A stronger reliance on exteroceptive information over internally generated signals in guiding perception is not evident in our data. Deficits in self-monitoring might therefore be modality specific or state dependant.

There is considerable variability in neurocognitive functioning within schizophrenia-spectrum disorders, and neurocognitive performance ranges from severe global impairment to normative performance. Few investigations of neurocognitive clusters have considered the degree to which deterioration relative to premorbid neurocognitive abilities is related to key illness characteristics. Moreover, while neurocognition and community functioning are strongly related, understanding of the sources of variability in the association between these two domains is also limited; it is unknown what proportion of participants would over-perform or under-perform the level of functioning expected based on current neurocognitive performance vs. lifelong attainment. This study examined data from 954 outpatients with schizophrenia-spectrum disorders across three previous studies. Neurocognition, community functioning, and symptoms were assessed. Neurocognitive subgroups were created based on current neurocognition, estimated premorbid IQ, and degree of deterioration from premorbid using z-score cut-offs; functional subgroups were created with cluster analysis based on the Specific Level of Functioning Scale and current neurocognition. The sample was neurocognitively heterogeneous; 65% displayed current neurocognitive impairment and 84% experienced some level of deterioration. Thirty percent of our sample was relatively higher functioning despite significant neurocognitive impairment. Individuals with better community functioning, regardless of neurocognitive performance, had lower symptom severity compared to those with worse functioning. These results highlight the variability in neurocognition and its role in functioning. Understanding individual differences in neurocognitive and functional profiles and the interaction between prior and current cognitive functioning can guide individualized treatment and selection of participants for clinical treatment studies.

Introduction

Clinical high risk for psychosis (CHR) is associated with mild cognitive impairments. Symptoms are clustered into positive, negative and disorganization symptoms. The association between specific symptom dimensions and cognitive functions remains unclear. The aim of this study was to investigate the associations between cognitive functions and positive, negative, and disorganization symptoms.

Method

53 CHR subjects fulfilling criteria for attenuated psychotic syndrome in the Structural Interview for Prodromal Syndromes (SIPS) were assessed for cognitive function. Five cognitive domain z-scores were defined by contrasting with observed scores of a group of healthy controls (n = 40). Principal Components Analyses were performed to construct general cognitive composite scores; one using all subtests and one using the cognitive domains. Associations between cognitive functions and symptoms are presented as Spearman's rank correlations and partial Spearman's rank correlations adjusted for age and gender.

Results

Positive symptoms were negatively associated with executive functions and verbal memory, and disorganization symptoms with poorer verbal fluency. Negative symptoms were associated with better executive functioning. There were no significant associations between the general cognitive composites and any of the symptom domains, except for a trend for positive symptoms.

Conclusion

In line with previous research, data indicated associations between positive symptoms and poorer executive functioning. Negative symptoms may not be related to executive functions in CHR the same way as in psychosis. Our results could indicate that attenuated positive symptoms are more related to cognitive deficits in CHR than positive symptoms in schizophrenia and FEP.