Deficits In Psychotic Disorders Research Articles

Association of obesity to reaction time and visual memory in schizophrenia

BackgroundBoth overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders. AimsOur aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder. MethodsThe study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory. ResultsObesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures. ConclusionsThe results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.

Protecting the Autonomy of Patients with Severe Mental Illness Through Psychiatric Advance Directive Peer-Facilitation

Protecting the Autonomy of Patients with Severe Mental Illness Through Psychiatric Advance Directive Peer-Facilitation

Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation to cognitive functioning.

Background:Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but its role in deep gray matter (DGM) regions is unclear.Aims:To evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction, and post-processing techniques.Methods:A 7-Tesla magnetic resonance imaging scanner combined with a lipid suppression coil and subject-specific water suppression pulses was used to acquire high-resolution magnetic resonance spectroscopic imaging data. Tissue fraction correction and registration to a standard brain were performed for group comparison in specifically delineated DGM regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status.Results:Average glutamate levels across DGM structures (i.e. caudate, pallidum, putamen, and thalamus) in mostly medicated patients with a psychotic disorder (n = 16, age = 33, 4 females) were lower compared to healthy controls (n = 23, age = 24, 7 females; p = 0.005, d = 1.06). Stratified analyses showed lower glutamate levels in the caudate (p = 0.046, d = 0.76) and putamen p = 0.013, d = 0.94). These findings were largely explained by age differences between groups. DGM glutamate levels were positively correlated with psychomotor speed (r(30) = 0.49, p = 0.028), but not with other cognitive domains.Conclusions:We find reduced glutamate levels across DGM structures including the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Despite limitations concerning age differences, these results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in psychotic disorders.

Amygdala connectivity during emotional face perception in psychotic disorders

Emotional face perception (EFP) deficits have been identified as a significant feature of psychotic disorders and are associated with symptoms and real-world functioning in these disorders. The amygdala is frequently implicated in EFP and bears extensive structural connectivity with other brain regions supporting EFP. Amygdala functional connectivity during attentional control of implicitly processed emotional faces in psychotic disorders is well examined. However, it is unclear whether amygdala functional connectivity while explicitly processing emotional faces contributes to EFP deficits in psychotic disorders. Further, it is unclear whether these connectivity differences are associated with symptoms or functioning and if these relationships are transdiagnostic across psychotic disorders. We used functional magnetic resonance imaging (fMRI) and seed-based functional connectivity analyses to examine connectivity of amygdala to other regions of the face processing network during an EFP task. The sample consisted of 55 cases with psychotic disorders and 29 participants with no history of psychosis (NP). Results indicated that, compared to NP, cases showed worse accuracy, greater inferior frontal gyrus (IFG) activation, and greater amygdala-insula connectivity while matching emotional and neutral faces. Additionally, worse accuracy, greater IFG activation, greater amygdala-insula and amygdala-IFG connectivity during emotional vs. neutral faces was associated with worse negative symptoms and greater deficits in social and global functioning in cases. Importantly, these relationships transcended diagnostic categories, and applied across psychotic disorders. The present study presents compelling evidence relating alterations in amygdala functional connectivity during explicit EFP with clinical and functioning deficits seen across psychotic disorders.

T200. Abnormal Thalamocortical Functional Connectivity and Sensory Gating Deficits in Psychotic Disorders: Are These Two Biomarkers Related?

T200. Abnormal Thalamocortical Functional Connectivity and Sensory Gating Deficits in Psychotic Disorders: Are These Two Biomarkers Related?

Alterations in intrinsic fronto-thalamo-parietal connectivity are associated with cognitive control deficits in psychotic disorders.

Despite a growing number of reports about alterations in intrinsic/resting brain activity observed in patients with psychotic disorders, their relevance to well-established cognitive control deficits in this patient group is not well understood. Totally 88 clinically stabilized patients with a psychotic disorder and 50 healthy controls participated in a resting-state magnetic resonance imaging study (rs-MRI) and performed an antisaccade task in the laboratory to assess voluntary inhibitory control ability. Deficits on this task are a well-established biomarker across psychotic disorders as we found in the present patient sample. First, regional cerebral function was evaluated by measuring the amplitude of low frequency fluctuations (ALFF) in rs-MRI BOLD signals. We found reduced ALFF in patients in regions known to be relevant to antisaccade task performance including bilateral frontal eye fields (FEF), supplementary eye fields (SEF) and thalamus. Second, areas with ALFF alterations were used as seed areas in whole-brain functional connectivity (FC) analysis. Altered FC was observed in a fronto-thalamo-parietal network that was associated with inhibition error rate in patients but not in controls. In contrast, faster time to generate a correct antisaccade was associated with FC in FEF and SEF in controls but this effect was not seen in patients. These findings establish a behavioral relevance of resting-state fMRI findings in psychotic disorders, and extend previous reports of alterations in fronto-thalamo-parietal network activation during antisaccade performance seen in task-based fMRI studies.

A Bayesian model comparison approach to test the specificity of visual integration impairment in schizophrenia or psychosis

Impaired visual integration is well documented in schizophrenia and related to functional outcomes. However, it is unclear if this deficit is specific to schizophrenia, or characteristic of psychosis more broadly. To address this question, this study used a Bayesian model comparison approach to examine the evidence of three grouping models of visual integration performance in 116 individuals with schizophrenia (SZ), schizoaffective disorder (SA), bipolar disorder (BD) with or without a history of prominent psychosis (BDP+ and BDP-, respectively), or no psychiatric diagnosis (healthy controls; HC). We compared: (1) Psychosis Model (psychosis, non-psychosis), where the psychosis group included SZ, SA, and BDP+, and the non-psychosis group included BDP- and HC; (2) Schizophrenia Model (SZ, non-SZ); and (3) DSM Model (SZ, SA, BD, HC). The relationship between visual integration and general cognition was also explored. The Psychosis Model showed the strongest evidence, and visual integration was associated with general cognition in participants with psychosis. The results were consistent with the Research Domain Criteria (RDoC) framework, indicating that visual integration impairment is characteristic of psychosis and not specific to SZ or DSM categories, and may share similar disease pathways with observed neurocognitive deficits in psychotic disorders.

S203. COMPENSATORY COGNITIVE APPROACHES TO IMPROVING FUNCTIONING IN PSYCHOSIS: SYSTEMATIC REVIEW AND META-ANALYSIS

BackgroundCognitive impairments in domains such as attention, memory, processing speed and executive functions are a central feature of psychotic disorders that have significant negative consequences for daily functioning, including activities of daily living, social and vocational roles. Compensatory approaches aim to minimise the impact of cognitive impairment on daily functioning through the use of aids or strategies to reduce cognitive load, in much the same way as glasses reduce the impact of vision impairment. The primary treatment target is real world community functioning and functional capacity, rather than cognition. There is now a need to synthesise the available evidence in this field so that treatment recommendations and future research directions can be better informed. A large body of research into compensatory approaches to cognition in psychosis exists, but this has never been comprehensively synthesised. The aim of this systematic review and meta-analysis is to examine the effects of compensatory approaches for cognitive deficits in psychotic disorders on i) functional outcomes and ii) other outcomes such as symptoms and quality of life.MethodsA systematic review and meta-analysis was conducted according to PRISMA guidelines. PsycINFO and MEDLINE electronic databases were searched from inception to October 2017 using multiple terms for ‘psychosis’, ‘cognition’ and ‘compensatory’. All papers retrieved from this search were double-screened and final inclusion/exclusion was determine by consensus. Data were double-extracted and risk of bias rated by two independent authors. Meta-analysis only included randomised-controlled trials. Standardised Mean Differences (SMD) were calculated to produce a single summary estimate using the random-effects model with 95% Confidence Intervals using Comprehensive Meta-Analysis (CMA) software. When means or standard deviations were not reported in the original articles, SMDs were calculated from data provided by the study authors.Results2192 articles were identified via electronic and manual searches. Forty-two papers describing 40 independent studies were included in the review: case studies (n=4), case series (n=2), uncontrolled single arm pilot studies (n=5), within-subjects designs (n=1), quasi-randomised trials (n=2), and randomised controlled trials (n=26). The types of compensatory interventions included environmental adaptation and supports, internal and external self-management strategies, and errorless learning. Compensatory interventions were associated with improvements in global functioning post intervention (N=1,449; SMD=0.506; 95%CI=0.347, 0.665; p<.001). Improvements in global symptoms (N=849; SMD=-0.297; 95%CI=-0.484, -0.111; p=.002) and positive symptoms (N=784; SMD=-0.227; 95%CI=-0.416, -0.038; p=.018) were also found. Compensatory interventions were not associated with improvements in negative symptoms (N=736; SMD=-0.162; 95%CI=-0.382, 0.058; p=.150). The heterogeneity of findings was low.DiscussionCompensatory approaches are effective for improving functioning in psychosis, with a medium effect size. General symptoms and positive symptoms appear to benefit from compensatory approaches, but compensatory approaches are not effective for improving negative symptoms. Future analyses will examine the durability of effects, effects of study quality and moderating factors such as pure vs. partially compensatory, treatment intensity/length, mode of delivery (group vs. individual), baseline functioning level and age of participants.

Visual and non-visual motion information processing during pursuit eye tracking in schizophrenia and bipolar disorder.

Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.

Low vitamin D levels linked to depression and cognitive deficits in psychotic disorders

Low vitamin D levels linked to depression and cognitive deficits in psychotic disorders

A comparative study of the working memory multicomponent model in psychosis and healthy controls

Working memory deficits are considered nuclear deficits in psychotic disorders. However, research has not found a generalized impairment in all of the components of working memory. We aimed to assess the components of the Baddeley and Hitch working memory model: the temporary systems—the phonological loop, the visuospatial sketchpad and the episodic buffer (introduced later by Baddeley)—and the central executive system, which includes four executive functions: divided attention, updating, shifting and inhibition. We assessed working memory performance in a sample of 21 patients with a psychotic disorder and 21 healthy controls. Patients also underwent a clinical assessment. Both univariate and repeated measures ANOVAs were applied to analyze performance in the working memory components between groups. Patients with a psychotic disorder underperformed compared to the controls in all of the working memory tasks, but after controlling for age and premorbid IQ, we only found a difference in performance in the N-Back task. Repeated measures ANCOVAs showed that patients also underperformed compared to the controls in the Digit span test and the TMT task. Not all of the components of working memory were impaired in the patients. Specifically, patients' performance was impaired in the tasks selected to assess the phonological loop and the shifting executive function. Patients' also showed worse performance than controls in the N-Back task, representative of the updating executive function. However, we did not find higher impairment in the patients' performance respect to controls when increasing the loading of the task.

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

A growing body of research suggests that schizophrenia and bipolar disorder share overlapping clinical, neurobiological, and genetic features, raising important questions about the boundaries and distinctiveness of these 2 major psychiatric disorders. A generalized cognitive impairment has long been understood to be a core feature of schizophrenia. More recently, it has become apparent that cognitive impairment also occurs in bipolar disorder, particularly in those patients with a history of psychotic symptoms. Whether a generalized deficit exists across a spectrum of psychotic disorders is less clearly established. Additionally, in the context of a broad impairment, it remains a significant challenge to identify deficits in specific cognitive processes that may have distinct neurochemical or regional brain substrates and linkages to particular risk-associated genetic factors. In this article, we review the findings from neuropsychological studies across a spectrum that includes schizophrenia, schizoaffective and bipolar disorders, and conclude the available evidence strongly supports that a generalized deficit is present across psychotic disorders that differs in severity more so than form. We then consider the implications of generalized and specific deficits in psychosis for 2 areas of research--the evaluation of pharmacological treatments targeting cognitive deficits, and the investigation of cognitive intermediate phenotypes in family genetic studies. Examples from the literature that touch on the relevance of the generalized deficit in these contexts are provided, as well as consideration for the continued need to identify specific impairments that are separable from the generalized deficit in order to advance drug and gene discovery.

Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis

Similar smooth pursuit eye tracking dysfunctions are present across psychotic disorders. They include pursuit initiation and maintenance deficits that implicate different functional brain systems. This candidate gene study examined psychosis-related genotypes regulating dopamine and glutamate neurotransmission in relation to these pursuit deficits. One hundred and thirty-eight untreated first-episode patients with a psychotic disorder were genotyped for four markers in DRD2 and four markers in GRM3. The magnitude of eye movement abnormality in patients was defined in relation to performance of matched healthy controls (N = 130). Eighty three patients were followed after 6 weeks of antipsychotic treatment. At baseline, patients with a -141C deletion in DRD2 rs1799732 had slower initiation eye velocity and longer pursuit latency than CC insertion carriers. Further, GRM3 rs274622_CC carriers had poorer pursuit maintenance than T-carriers. Antipsychotic treatment resulted in prolonged pursuit latency in DRD2 rs1799732_CC insertion carriers and a decline in pursuit maintenance in GRM3 rs6465084_GG carriers. The present study demonstrates for the first time that neurophysiological measures of motor and neurocognitive deficits in patients with psychotic disorders have different associations with genes regulating dopamine and glutamate systems, respectively. Alterations in striatal D2 receptor activity through the -141C Ins/Del polymorphism could contribute to pursuit initiation deficits in psychotic disorders. Alterations in GRM3 coding for the mGluR3 protein may impair pursuit maintenance by compromising higher perceptual and cognitive processes that depend on optimal glutamate signaling in corticocortical circuits. DRD2 and GRM3 genotypes also selectively modulated the severity of adverse motor and neurocognitive changes resulting from antipsychotic treatment.

Does operational diagnosis of schizophrenia significantly impact intellectual deficits in psychotic disorders?

Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. Using Wechsler Adult Intelligence Scale-Revised (WAIS-R) data for 55 inpatients with schizophrenia and 28 inpatients with non-schizophrenic psychotic disorders (NSPD) (schizophreniform disorder, brief psychotic disorder, delusional disorder, psychotic disorder due to a general medical condition, and psychotic disorders not otherwise specified), intelligence performance was compared between schizophrenia and NSPD and among different subtypes of schizophrenia. There were no significant differences in intelligence quotient (IQ), verbal IQ (VIQ) and performance IQ (PIQ) discrepancy, and subtest scores of WAIS-R between the patients with schizophrenia and those with NSPD. These diagnostic groups were not discriminated well by any WAIS-R variables. Schizophrenia patients with prominent negative symptoms, on the other hand, had a significantly larger IQ discrepancy (VIQ > PIQ) than those without prominent negative symptoms and NSPD patients. Intelligence performance in schizophrenia did not differ with respect to diagnostic subtypes and longitudinal courses. The current study failed to show diagnostic usefulness of WAIS-R in discriminating schizophrenia and other psychoses. A diagnosis of schizophrenia does not significantly impact intellectual deficits in psychotic disorders.