Functional Outcome In Schizophrenia Research Articles

Combining actigraphy, ecological momentary assessment and neuroimaging to study apathy in patients with schizophrenia

BackgroundApathy can be defined as a reduction of goal-directed behavior and is a strong predictor for poor functional outcome in schizophrenia. However, no objective measure of apathy has been identified and assessment is limited to retrospective interview-based ratings. Here we aimed to identify more precise objective readouts of apathy for translational research and clinical practice. MethodsWe employed a combined approach including interview-based ratings of the two negative symptom factors apathy and diminished expression, actigraphy based measures of spontaneous motor activity and the evaluation of daily activities using ecological momentary assessment. Furthermore, a functional magnetic resonance imaging task for reward anticipation was applied to investigate shared and divergent neural correlates of interview-based and behaviorally measured apathy. ResultsWe found in 18 schizophrenia patients with high interview-based apathy levels that motor activity was negatively correlated with apathy but not with diminished expression. In contrast, measures of daily activities were not associated with apathy. Neural activation during reward anticipation revealed an association between hypoactivation of the ventral striatum and interview-based apathy as well as hypoactivation of the inferior frontal gyrus and motor activity level. ConclusionsSpontaneous motor activity is an objective readout of apathy, which was specific and not present for diminished expression. On a neural level, interview-based and objective measures of apathy showed divergent neural correlates in the cortical-striatal network, which suggests dissociable neural processes. Finally, motor activity provides a promising readout for quantifying apathy in both translational research and clinical practice.

Normal-range verbal-declarative memory in schizophrenia.

Cognitive impairment is prevalent and related to functional outcome in schizophrenia, but a significant minority of the patient population overlaps with healthy controls on many performance measures, including declarative-verbal-memory tasks. In this study, we assessed the validity, clinical, and functional implications of normal-range (NR), verbal-declarative memory in schizophrenia. Performance normality was defined using normative data for 8 basic California Verbal Learning Test (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000) recall and recognition trials. Schizophrenia patients (n = 155) and healthy control participants (n = 74) were assessed for performance normality, defined as scores within 1 SD of the normative mean on all 8 trials, and assigned to normal- and below-NR memory groups. NR schizophrenia patients (n = 26) and control participants (n = 51) did not differ in general verbal ability, on a reading-based estimate of premorbid ability, across all 8 CVLT-II-score comparisons or in terms of intrusion and false-positive errors and auditory working memory. NR memory patients did not differ from memory-impaired patients (n = 129) in symptom severity, and both patient groups were significantly and similarly disabled in terms of functional status in the community. These results confirm a subpopulation of schizophrenia patients with normal, verbal-declarative-memory performance and no evidence of decline from higher premorbid ability levels. However, NR patients did not experience less severe psychopathology, nor did they show advantage in community adjustment relative to impaired patients. (PsycINFO Database Record

Resting state perfusion in the language network is linked to formal thought disorder and poor functional outcome in schizophrenia.

ObjectiveFormal thought disorder (FTD) is a core symptom in schizophrenia. Here, we focus on resting state cerebral blood flow (rCBF) linked to dimensions of FTD.MethodsWe included 47 schizophrenia spectrum patients and 30 age‐ and gender‐matched healthy controls. We assessed FTD with the assessment of thought, language, and communication (TLC) and imaging on a 3T MRI scanner. Within patients, we tested the association of FTD dimensions and in a subgroup (n = 27) the association of functional outcome after 6 months with whole brain rCBF.ResultsNegative FTD was most prominently associated with perfusion within the superior temporal gyrus, while positive FTD was associated with perfusion within the supplementary motor area, and inferior frontal gyrus. Perfusion within the left supramarginal gyrus was associated with social functioning after 6 months.ConclusionsDistinguishable associations of rCBF with FTD dimensions point to distinct underlying pathophysiology. The location of aberrant perfusion patterns suggests that negative FTD might reflect defective access to semantic memory while positive FTD likely reflects defective suppression of irrelevant information during increased speech production. Finally, the neural correlates of thought block were also predictive of poor functional outcome. Thus, functional outcome and distinct FTD dimensions may share some pathophysiology.

Body language reading of emotion in schizophrenia: Associations withsymptoms and functional outcome.

Our aim was to explore how body language reading of emotion relates to neurocognition, symptoms and functional outcome in schizophrenia. Fifty-four individuals with schizophrenia and eighty-four healthy controls participated in the study. Emotion perception was assessed with a point-light display (PLD) task, the Emotion in Biological Motion (EmoBio) test, neurocognition was measured with the MATRICS Consensus Cognitive Battery (MCCB), and functioning was indexed by one measure of functional capacity and by one self-report questionnaire. Clinical symptoms were assessed with a five factor Positive and Negative Syndrome Scale (PANSS) symptoms model. Participants with schizophrenia had impaired body language reading of emotions compared to healthy controls (Cohen's d = 0.69). In participants with schizophrenia, emotion perception was associated with neurocognition (r = 0.42), functional capacity (r = 0.27) and disorganization symptoms (r = -0.27). Mediation analyses showed that disorganization symptoms mediated the effects of emotion perception and neurocognition, respectively, on social functional capacity. These results suggest that in individuals with schizophrenia, reduced emotion perception from body movements has negative consequences for functional outcome, but that the effect is mediated through disorganization symptoms.

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function

ImportanceSchizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction.ObjectiveTo identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains.Design, Setting, and ParticipantsCombining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Main Outcomes and MeasuresGenetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined.ResultsAmong the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10−7), general cognitive function (z score, –4.43; P = 9.42 × 10−6), and verbal-numerical reasoning (z score, –5.43; P = 5.64 × 10−8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain.Conclusions and RelevanceThe discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

Potential drug targets and treatment of schizophrenia.

Schizophrenia is one of the most prevalent chronic psychiatric disorders that affect 1% of the world's population. Despite its societal burden, pathophysiology of schizophrenia remains poorly understood. Currently available drugs predominantly control positive symptoms, and often have no or poor control on negative and related cognitive symptoms, which strongly affect functional outcome in schizophrenia. The present article is an attempt to provide a critical review of recent hypothesis to understand pathophysiology of schizophrenia and to highlight exploitable molecular drug targets other than dopaminergic systems to treat and manage schizophrenia effectively.

Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia

Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1+/− mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory. Here, we further characterize performance of these mice by following the preclinical guidelines recommended by the ‘Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)’ and ‘Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS)’ initiatives to maximize translational value. Brd1+/− mice exhibit relational encoding deficits, compromised working and long term memory, as well as impaired executive cognitive functioning with cognitive behaviors relying on medial prefrontal cortex being particularly affected. Akin to patients with schizophrenia, the cognitive deficits displayed by Brd1+/− mice are not global, but selective. Our results underline the value of Brd1+/− mice as a promising tool for studying the neurobiology of cognitive deficits in schizophrenia.

Supplementing intensive targeted computerized cognitive training with social cognitive exercises for people with schizophrenia: An interim report.

Individuals with schizophrenia demonstrate cognitive, social cognitive, and motivational deficits that contribute to impairment in real-world functioning. In the current study, we investigated the effects of supplementing computerized neurocognitive training with social cognitive exercises, as compared with neurocognitive training alone. In this ongoing, double-blind, randomized controlled trial of 111 participants with psychosis, we compare the effects of supplementing intensive targeted cognitive training with social cognitive training exercises (TCT + SCT) with the effects of targeted cognitive training alone (TCT-only). Participants were assessed on cognition, symptoms, functional capacity, and functional outcomes, as well as social cognition and measures related to reward processing. Both treatment groups showed significant improvement in multiple cognitive domains and improvement in functional capacity. However, as predicted, TCT + SCT group participants showed significant improvement in prosody identification and reward processing relative to TCT-only participants. Our findings indicate that supplementing intensive computerized cognitive training with social cognitive exercises in people with psychosis confers greater benefits in prosody identification and reward processing relative to cognitive training alone, even though both approaches drive significant improvements in cognition and functional capacity. Impairments in both prosody identification and reward processing have been associated with greater negative symptoms and poorer functional outcomes in schizophrenia, raising the possibility that this form of treatment may lead to better long-term outcomes than traditional cognitive training approaches. Follow-up assessments will determine whether results are durable and generalize over time to improvements in symptoms and functioning. (PsycINFO Database Record

A Systematic and Meta-analytic Review of Neural Correlates of Functional Outcome in Schizophrenia.

Individuals with schizophrenia are burdened with impairments in functional outcome, despite existing interventions. The lack of understanding of the neurobiological correlates supporting adaptive function in the disorder is a significant barrier to developing more effective treatments. This research conducted a systematic and meta-analytic review of all peer-reviewed studies examining brain-functional outcome relationships in schizophrenia. A total of 53 (37 structural and 16 functional) brain imaging studies examining the neural correlates of functional outcome across 1631 individuals with schizophrenia were identified from literature searches in relevant databases occurring between January, 1968 and December, 2016. Study characteristics and results representing brain-functional outcome relationships were systematically extracted, reviewed, and meta-analyzed. Results indicated that better functional outcome was associated with greater fronto-limbic and whole brain volumes, smaller ventricles, and greater activation, especially during social cognitive processing. Thematic observations revealed that the dorsolateral prefrontal cortex, anterior cingulate, posterior cingulate, parahippocampal gyrus, superior temporal sulcus, and cerebellum may have role in functioning. The neural basis of functional outcome and disability is infrequently studied in schizophrenia. While existing evidence is limited and heterogeneous, these findings suggest that the structural and functional integrity of fronto-limbic brain regions is consistently related to functional outcome in individuals with schizophrenia. Further research is needed to understand the mechanisms and directionality of these relationships, and the potential for identifying neural targets to support functional improvement.

The Functional Significance of Affect Recognition, Neurocognition, and Clinical Symptoms in Schizophrenia.

ObjectivesThe complex relationship and exact extent of the contribution of plausible indictors to social functional outcome in schizophrenia remain unclear. The present study aimed to explore the functional significance of clinical symptoms, neurocognition, and affect recognition simultaneously in schizophrenia.MethodsThe clinical symptoms, basic neurocognition, facial emotion recognition, and social functioning of 154 subjects, including 74 with schizophrenia and 80 nonclinical comparisons, were assessed.ResultsWe observed that various subdomains of social functioning were extensively related to general intelligence, basic neurocognition, facial emotion recognition, and clinical symptoms, with different association patterns. Multivariate regression analyses revealed that years of education, age, sustained attention, working memory, and facial emotion recognition were significantly associated with global social functioning in schizophrenia.ConclusionOur findings suggest that affect recognition combined with nonsocial neurocognition demonstrated a crucial role in predicting global social function in schizophrenia.

Confirmatory factor analysis of the quality of life scale and new proposed factor structure for the quality of life scale-revised

The Quality of Life Scale (QLS) is a frequently used semistructured interview for the assessment of functional outcomes in schizophrenia. Despite the use of the QLS for over 30years, the original 4-factor structure of the instrument (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities) has not been rigorously examined. Exploratory factor analyses (EFAs) and confirmatory factor analyses (CFAs) were used to evaluate the factor structure of the QLS in two independent datasets, including a mixed diagnostic sample of multi-episode participants (N=247), and a sample of individuals with a first episode of psychosis (N=337). A CFA with the first dataset indicated a poor fit for the 4-factor model of the QLS. Subsequent EFAs on this dataset led to a more promising 3-factor solution including 16/21 of the QLS items, which were similar to the first 3 of 4 factors originally proposed for the QLS. CFAs on the same dataset indicated that the 3-factor model for the QLS-Revised (QLS-R) fit the data well. This factor structure was evaluated with the second dataset using CFA and was also found to be fit the data well. The results support the robustness of the 3-factor model of the QLS-R in schizophrenia and mixed diagnostic samples. Future research should evaluate the validity of the 3-factor model of the QLS-R, and consider the merits of changing the name of the Intrapsychic Foundations factor to Motivation.

S.09.01 - Negative symptoms domains: pathways to functional outcome in schizophrenia

This study evaluates the capability of soil water content predicted from remote sensing to indicate the soil/canopy water content at short time and space scale, through comparisons with daily soil moisture data determined in situ, using dielectric devices. Daily aqua moderate resolution imaging spectroradiometer (MODIS) normalized difference vegetation index (NDVI) and the diurnal (daytime and night time) land surface temperature difference (DLST) are employed to retrieving daily volumetric soil moisture content (θ) at Sparta experimental station, during the period June-August, of the years 2010, 2011, 2012 and 2014. Using the concept of apparent thermal inertia (ATI) in the remotely sensed topsoil moisture saturation index, daily θ is obtained from DLST and the volumetric saturated and residual soil moisture content and is compared with the experimental values of volumetric soil moisture content (SM) measured at various depths (10, 20, 30, 40, 60, 80 and 100 cm). Simple relationships are also calibrated between SM and ATI or DLST or NDVI during the years 2010, 2011 and 2014 and are tested for predicting θ, during the year 2012. Especially the three first models predict θ satisfactorily as compared with the measured SM and hence they can offer a considerable guidance in irrigated agriculture and other related fields.

Cognitive insight and functional outcome in schizophrenia; a multi-center collaborative study with the specific level of functioning scale–Japanese version

The Specific Levels of Functioning Scale (SLOF) has been reported to provide a measure of social function in patients with schizophrenia. The aim of this multi-center study was to determine convergent validity of the Japanese version of SLOF, and if cognitive insight would be associated with social function. Fifty-eight patients with schizophrenia participated in the study. Social function, neurocognition, and daily activity skills were evaluated by the Social Functioning Scale (SFS), Brief Assessment of Cognition in Schizophrenia (BACS) and UCSD Performance-based Skills Assessment-Brief (UPSA-B), respectively. We also assessed cognitive insight with the Beck Cognitive Insight Scale (BCIS). Significant relationships were noted between scores on the SLOF vs. those of the SFS, BACS, UPSA-B, and BCIS. Specifically, the correlation between performance on the UPSA-B and SLOF scores was significantly more robust compared to the correlation between performance on the UPSA-B and scores on the SFS. Similarly, the correlation between scores on the BACS and SLOF tended to be more robust than that between the BACS and SFS. Importantly, while the correlation between scores on the BCIS and SLOF reached significance, it was not so between scores on the BCIS and SFS. The SLOF Japanese version was found to provide a measure of social consequences in patients with schizophrenia. Importantly, this study is the first to indicate the relationship between cognitive insight and social function evaluated by the SLOF. This finding is consistent with the observation that SLOF scores were considerably associated with performances on objective functional measures.

Effects of Anticholinergic Medications in Schizophrenia Patients

Cognitive impairment affects a range of functional outcomes in schizophrenia. In addition, people with schizophrenia often take antipsychotics with

Gesture Performance in Schizophrenia Predicts Functional Outcome After 6 Months.

The functional outcome of schizophrenia is heterogeneous and markers of the course are missing. Functional outcome is associated with social cognition and negative symptoms. Gesture performance and nonverbal social perception are critically impaired in schizophrenia. Here, we tested whether gesture performance or nonverbal social perception could predict functional outcome and the ability to adequately perform relevant skills of everyday function (functional capacity) after 6 months. In a naturalistic longitudinal study, 28 patients with schizophrenia completed tests of nonverbal communication at baseline and follow-up. In addition, functional outcome, social and occupational functioning, as well as functional capacity at follow-up were assessed. Gesture performance and nonverbal social perception at baseline predicted negative symptoms, functional outcome, and functional capacity at 6-month follow-up. Gesture performance predicted functional outcome beyond the baseline measure of functioning. Patients with gesture deficits at baseline had stable negative symptoms and experienced a decline in social functioning. While in patients without gesture deficits, negative symptom severity decreased and social functioning remained stable. Thus, a simple test of hand gesture performance at baseline may indicate favorable outcomes in short-term follow-up. The results further support the importance of nonverbal communication skills in subjects with schizophrenia.

Psychoéducation et troubles de l’insight dans la schizophrénie

Schizophrenia is characterized not only by symptoms, but also by a reduced insight that contributes to functional outcomes through a bad acceptation of the disease and a low involvement in treatment and care. Functional outcomes of schizophrenia are conditioned by the acceptance of the troubles, by the involvement in psychopharmacological treatment and in psychosocial care and by the expressed emotion level of the family. Psychoeducation improves adherence to treatment. Psychoeducation lowers relapse rate. All the patients suffering from schizophrenia and their families should benefit from psychoeducation.

Social Cognition, Negative Symptoms and Psychosocial Functioning in Schizophrenia

Although functional recovery could be advocated as an achievable treatment goal, many effective interventions for the treatment of psychotic symptoms, such as antipsychotic drugs, may not improve functioning. The last two decades of cognitive and clinical research on schizophrenia were a turning point for the firm acknowledgment of how relevant social cognitive deficits and negative symptoms could be in predicting psychosocial functioning. The relevance of so cial cognition dysfunction in schizophrenia patients’ daily living is now unabated. In fact, social cognition deficits could be the most significant predictor of functionality in patients with schizophrenia, non-redundantly with neurocogni tion. Emerging evidence suggests that negative symptoms appear to play an indirect role, mediating the relationship between neurocognition and social cognition with functional outcomes. Further explorations of this mediating role of negative symptoms have revealed that motivational deficits appear to be particularly important in explaining the relationship between both neurocognitive and social cognitive dysfunction and functional outcomes in schizophrenia. In this paper we will address the relative contribution of two key constructs—social cognitive deficits and negative symptoms, namely how intertwined they could be in daily life functioning of patients with schizophrenia.

Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia

Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia.

Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study

Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~30dB(A); urban noise: building site noise, 68–78dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68–78dB(A)], 7–14days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits.

Defeatist Performance Beliefs, Negative Symptoms, and Functional Outcome in Schizophrenia: A Meta-analytic Review.

Negative symptoms are a strong predictor of poor functional outcome in people with schizophrenia. Unfortunately there are few effective interventions for either negative symptoms or functional outcome, despite the identification of potential mechanisms. Recent research, however, has elucidated a new potential mechanism for negative symptoms and poor functional outcome: defeatist performance beliefs (DPB), or negative thoughts about one's ability to successfully perform goal-directed behavior that can prevent behavior initiation and engagement. We conducted 2 meta-analyses examining the relationship between DPB and both negative symptoms (n = 10 studies) and functional outcome (n = 8 studies) in people with schizophrenia. We found a small effect size for the relationship between DPB and negative symptoms, regardless of how negative symptoms were measured. We also found a small effect size for the relationship between DPB and functional outcome, which was significantly moderated by the method of assessing DPB and moderated by the sex composition of the study at a trend level. These findings highlight the potential of targeting DPB in psychosocial interventions for both negative symptoms and functional outcome.