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Cognitive impairment is a core feature of schizophrenia and impacts negatively the functioning of affected individuals. Cognitive decline correlates with aging, and is the primary cause of loss of independence and reduced quality of life. The klotho gene is a key modulator of aging, with expression deficiency resulting in premature aging, while overexpression extends lifespan and enhances cognition. A haplotype and functional human variant of the gene, KL-VS, increases expression and promotes longevity. KL-VS heterozygosity is associated with enhanced cognition and a larger volume of the right dorsolateral prefrontal cortex, a region involved in planning and decision-making, which is especially susceptible to shrinkage with age. We examined the effect of KL-VS heterozygosity on cognition in 497 schizophrenia patients and 316 healthy controls from the Western Australian Family Study of Schizophrenia (WAFSS) who had been comprehensively characterised by neurocognitive tests and classified into cognitively deficient (CD) and cognitively "spared" (CS) clusters. An older, cognitively normal population sample from the Health in Men Study (HIMS) was included to allow assessment of heterozygosity and memory in aged individuals. We show that heterozygosity is associated with better learning and memory in the younger WAFSS healthy controls but not in the aging HIMS sample. However, in schizophrenia patients, KL-VS has a selective effect on memory, with heterozygotes in CD and CS clusters performing worse than non-carriers. This effect was significant and more severe in the CD cluster, reinforcing the utility of subtyping patients into CD and CS clusters that may differ in their genetic underpinnings., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Loneliness involves subjective, rather than objective, social isolation and has a range of negative effects on mental and physical functioning. The purpose of this study was to examine the prevalence of loneliness in psychotic disorders and its association with symptoms and cognitive performance., Method: Data were drawn from the second Australian National Survey of Psychosis and comprised responses from 1642 participants with an International Classification of Diseases 10 diagnosis of psychotic disorder who had completed a semi-structured interview of symptoms and social functioning (including loneliness), along with standardized assessments of current (digit symbol coding; DSC) and premorbid (National Adult Reading Test) cognitive ability. We examined the prevalence of loneliness across the diagnostic categories of psychosis, and its association with psychotic and non-psychotic symptoms and digit symbol coding scores., Results: The prevalence of loneliness was high, ranging from 74.75% in participants with delusional disorders to 93.8% in depressive psychosis, and was significantly higher than in the general population. Loneliness was also significantly associated with anhedonia and subjective thought disorder. Participants feeling socially isolated/lonely for company had significantly lower DSC scores than those who only felt lonely occasionally. Unexpectedly, participants who reported not feeling lonely had the lowest DSC scores., Conclusions: Loneliness is common across all psychotic disorders, particularly in depressive psychosis. It is specifically associated with ongoing loss of pleasure and disordered thoughts as well as impairment in current cognitive functioning. However, poor cognitive functioning is not inevitably associated with loneliness. Implications for personalized treatment of psychosis are discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Voices provide a wealth of socially-relevant information, including cues to a speaker's identity and emotion. Deficits recognising emotion from voice have been extensively described in schizophrenia, and linked specifically to auditory hallucinations (AH), but relatively little attention has been given to examining the ability to analyse speaker identity. Hence, the current study assessed the ability to discriminate between different speakers in people with schizophrenia (including 33 with and 32 without AH) compared to 32 healthy controls. Participants rated the degree of perceived identity similarity of pairs of unfamiliar voices pronouncing three-syllable words. Multidimensional scaling of the dissimilarity matrices was performed and the resulting dimensions were interpreted, a posteriori, via correlations with acoustic measures relevant to voice identity. A two-dimensional perceptual space was found to be appropriate for both schizophrenia patients and controls, with axes corresponding to the average fundamental frequency (F0) and formant dispersion (D(f)). Patients with schizophrenia did not differ from healthy controls in their reliance on F0 in differentiating voices, suggesting that the ability to use pitch-based cues for discriminating voice identity may be relatively preserved in schizophrenia. On the other hand, patients (both with and without AH) made less use of D(f) in discriminating voices compared to healthy controls. This distorted pattern of responses suggests some potentially important differences in voice identity processing in schizophrenia. Formant dispersion has been linked to perceptions of dominance, masculinity, size and age in healthy individuals. These findings open some interesting new directions for future research., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

While the majority of cognitive studies on auditory hallucinations (AHs) have been conducted in schizophrenia (SZ), an increasing number of researchers are turning their attention to different clinical and nonclinical populations, often using SZ findings as a model for research. Recent advances derived from SZ studies can therefore be utilized to make substantial progress on AH research in other groups. The objectives of this article were to (1) present an up-to-date review regarding the cognitive mechanisms of AHs in SZ, (2) review findings from cognitive research conducted in other clinical and nonclinical groups, and (3) integrate these recent findings into a cohesive framework. First, SZ studies show that the cognitive underpinnings of AHs include self-source-monitoring deficits and executive and inhibitory control dysfunctions as well as distortions in top-down mechanisms, perceptual and linguistic processes, and emotional factors. Second, consistent with SZ studies, findings in other population groups point to the role of top-down processing, abnormalities in executive inhibition, and negative emotions. Finally, we put forward an integrated model of AHs that incorporates the above findings. We suggest that AHs arise from an interaction between abnormal neural activation patterns that produce salient auditory signals and top-down mechanisms that include signal detection errors, executive and inhibition deficits, a tapestry of expectations and memories, and state characteristics that influence how these experiences are interpreted. Emotional factors play a particular prominent role at all levels of this hierarchy. Our model is distinctively powerful in explaining a range of phenomenological characteristics of AH across a spectrum of disorders.

The continuum model of psychosis has been extremely influential. It assumes that psychotic symptoms, such as auditory verbal hallucinations (AVH), are not limited to patients with psychosis but also occur in healthy, non-clinical individuals - suggesting similar mechanisms of origin. Recent debate surrounding this model has highlighted certain differences, as well as similarities, in the phenomenology of AVH in clinical and non-clinical populations. These findings imply that there may, in fact, be only partial overlap of the mechanism(s) involved in generating AVH in these groups. We review evidence of continuity or similarity, and dissimilarity, in cognitive, and related neural processes, underlying AVH in clinical and non-clinical samples. The results reveal some shared (intrusive cognitions, inhibitory deficits) and some distinct (aspects of source memory and cerebral lateralization) mechanisms in these groups. The evidence, therefore, supports both continuous and categorical models of positive psychotic symptoms. The review considers potential risks of uncritical acceptance of the continuum model and highlights some important methodological issues for future research., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Auditory hallucinations are generally defined as false perceptions. Recent developments in auditory neuroscience have rapidly increased our understanding of normal auditory perception revealing (partially) separate pathways for the identification ("what") and localization ("where") of auditory objects. The current review offers a reexamination of the nature of auditory hallucinations in schizophrenia using this object-based framework. First, the structural and functional organization of auditory what and where pathways is briefly described. Then, using recent functional neuroimaging data from healthy subjects and patients with schizophrenia, key phenomenological features of hallucinations are linked to abnormal processing both within and between these pathways. Finally, current cognitive explanations of hallucinations, based on intrusive cognitions and impaired source memory, are briefly outlined and set within this framework to provide an integrated cognitive neuropsychological model of auditory hallucinations.

Impairments in intentional-but not unintentional-inhibition have been found in schizophrenia, and are thought to contribute to the presence of psychotic symptoms. However, it was previously unknown whether this intentional cognitive control impairment extends to intentional resistance to interference-another form of cognitive control. The current study resolved this issue through administering two cognitive control measures: one with a high intentional resistance to interference demand and the other with a high unintentional inhibition demand, to schizophrenia (n = 61) and healthy control (n = 34) participants. Consistent with previous findings, schizophrenia participants' performance on the measures with a high unintentional inhibition demand was intact; however, they were impaired on the task with high intentional resistance to interference demands compared with controls. This latter finding suggests that intentional cognitive control impairments previously found in schizophrenia are not specific to inhibition, but instead are more general, including both processes requiring inhibition (as consistently reported in the literature) and resistance to interference (as found in the current study).

Background: In this study, we conducted a broad investigation of neuropsychological functioning in schizophrenia patients with first-rank (passivity) symptoms (FRS) using standardized cognitive tests. We focused on 3 neuropsychological domains, partly informed by 3 broad hypotheses concerning the pathogenesis of FRS. We tested predictions that patients with FRS would show: (i) memory deficits consistent with abnormalities in medial temporal lobe functioning; (ii) reduced cerebral lateralization on tasks of motor and language functions, and (iii) deficits on tasks of executive functions as a measure of the integrity of the prefrontal cortex for supporting self-monitoring processes., Sampling and Methods: In 2 parallel studies, we administered a range of neuropsychological tests to patients with FRS (sample A = 17, sample B = 15) and without FRS (sample A = 28, sample B = 20) and to healthy controls (sample A = 109, sample B = 22)., Results: The results showed reduced cerebral lateralization in patients with FRS, but there were no memory deficits or executive dysfunctions relative to patients without FRS. An unexpected finding was that, on many cognitive tasks, the performance of the patients with FRS was relatively spared compared to that of the patients without FRS. These results could not be accounted for by demographic features or medication effects., Conclusions: Our results provide qualified support for the reduced lateralization hypothesis. Analyses of performance across neuropsychological domains showed that generalized deficit is not a sufficient explanation for the occurrence of FRS., ((c) 2008 S. Karger AG, Basel.)

Background: Visuospatial working memory is not a unitary sketch pad but comprises independent dimensions of target distance and direction and at least two levels of detail (fine-grained and category level). The aim of this study was to examine these multiple aspects of encoding in patients with schizophrenia using a modified delayed response task., Method: 42 patients with schizophrenia and 48 healthy controls pointed, as accurately as possible from a fixed starting position, to the visual location of target stimuli presented to a touch-sensitive screen. An adaptive staircase procedure was used to equate stimulus duration for each individual. Encoding accuracy and maintenance of distance (mm) and direction ( degrees ) information was examined following a 0-second (immediate) or 4-second (unfilled) delay. Analyses utilized both absolute (unsigned) and signed data., Results: The results showed that the average duration required to detect a target was significantly longer in patients than controls. When stimulus duration was equated, (a) the absolute accuracy of distance and direction responses was not significantly different between groups at 0-second delay but was significantly reduced at 4-second delay in patients with schizophrenia, and (b) signed direction errors at 4-second delay were significantly different between groups at stimulus angles greater than 90 degrees ., Conclusions: The findings challenge previous suggestions of deficits in fine-grained encoding of spatial information in schizophrenia but confirm a difficulty maintaining both direction and distance details in working memory. Imprecision in spatial memory in schizophrenia also introduced greater bias from category level (prior) representations, especially in left hemi-space.

There is a growing literature describing a subgroup of "high-functioning" people with schizophrenia who show preserved intellectual ability (IQ). A detailed characterisation of the cognitive abilities of this group may be important in targeting appropriate treatment, management and services for patients with schizophrenia. It is a widely held belief that variation in cognitive processing speed is the basis of individual differences in intelligence. The main objective of this study was to identify subgroups of schizophrenia patients with preserved (N=45), deteriorated (N=47) and compromised (N=17) intellect in order to study whether these subgroups differ in specific cognitive abilities (e.g. executive functions) or in general cognitive processing speed, as measured with an inspection time (IT) task. The patients who displayed an average estimated premorbid IQ, with no evidence of IQ decline (premorbid-current IQ difference <10 points), were found to show better performance on measures of executive function (continuous performance task, verbal fluency) compared with patients in the deteriorated and compromised subgroups. Nevertheless, this represented significantly impaired performance relative to healthy controls. In contrast, the average inspection times of patients with preserved IQ were as slow as those obtained in the deteriorated or compromised groups, indicating that high functioning patients are impaired in terms of cognitive processing speed. Furthermore, the average IT for all schizophrenia groups was significantly slower than that of healthy controls. These findings suggest that high functioning patients with schizophrenia exhibit enduring cognitive difficulties that may impact on their ability to benefit from rehabilitation interventions.

The current study aimed to provide evidence for the context-memory hypothesis, which proposes that schizophrenia is linked to a deficit in retrieving contextual information and in binding the different components of a memory together. A new task was developed in which memory for the content of events could be assessed in conjunction with memory for both source and temporal information. Forty-three patients with schizophrenia and 24 normal controls took part in the study. Patients were found to be less accurate in identifying the source and temporal context of events. Furthermore, whereas controls tended to identify correctly both source and temporal context of events, patients tended to have a more fractionated recollection of those events. The study provides support for the context-memory hypothesis by demonstrating that patients with schizophrenia show a fundamental deficit in binding contextual cues together to form a coherent representation of an event in memory.

Introduction . The aim of this study was to re-examine the role of cognitive processing speed in the vulnerability to schizophrenia, using an inspection time (IT) task that does not require a speeded manual response. Since IT consistently correlates with intelligence, the relationship between IT and general intelligence was also explored. Methods . Patients with schizophrenia were compared with unaffected siblings of schizophrenia patients and healthy controls on a visual IT task. Both speed and variability of IT performance were examined. Current intellectual ability (IQ) was estimated with the Shipley Institute of Living Scale (SILS), which yields separate assessments of verbal and abstraction abilities. Results . Schizophrenia patients produced ITs that were significantly slower and more variable than either unaffected siblings or healthy controls. These results are not related to demographic or clinical variables. A significant negative correlation was obtained between IT and IQ; specifically, longer IT values were associated with abstraction scores only. Conclusions . These findings confirm that basic cognitive processing efficiency is impaired in patients with schizophrenia. In contrast, ITs in unaffected siblings did not differ from healthy controls, in line with their better IQ test scores. Implica tions for models of general and specific heritable dimensions in schizophrenia are discussed. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine the association between lifetime cannabis use and estimates of both premorbid and current cognitive function in psychotic disorders in an Australian cohort.Methods: In an Australian multicenter cohort, 1237 participants with an established ICD-10 diagnosis of psychotic disorder were categorised according to history of lifetime cannabis use (non-users, n=354; cannabis users, n=221; cannabis dependency, n=662). Groups were analyzed according to available indices of cognitive ability: the National Adult Reading Test - Revised (NART-R) for ability prior to illness onset; and the Digit Symbol Coding Test (DSCT) for current ability. Two-way analysis of variance was conducted without any covariate, followed by a two-way analysis of covariance (using age, age at onset of psychiatric illness, premorbid IQ and the Socio-Economic Index for Areas (SEIFA) rankings).Results: Whilst there appeared to be a significant association between cannabis use and mean DSCT (higher DSCT scores in cannabis using groups) F(2,1080)=9.478, p<0.001, η2=0.017), once covariates were used in the analysis there were no significant differences between groups in mean DSCT scores (F(2,1011)=0.929, p=0.395, η2=0.002). Similarly there were no differences between groups in mean NART scores once, age, age at illness onset and SEIFA rankings were used as covariates (F(2,1032)=1.617, p=0.199, η2=0.003).Conclusions: Confounding variables underpin the association between cannabis use and cognitive function in psychotic disorders. Taken together, it would appear that cannabis use or dependence has no additive effect on cognitive dysfunction in these disorders. [ABSTRACT FROM AUTHOR]