Cognitive Impairment In Psychosis Research Articles

Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition

ObjectiveContemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ. MethodsThe study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively). ResultsPatients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05). ConclusionOur study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.

Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study.

Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. The total scores on the measures of cognition and social exclusion were strongly associated (β = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

The use of implementation science to close the research-to-treatment gap for cognitive impairment in psychosis.

For people living with psychosis, cognitive impairment is common and can have significant impacts for functional recovery, impacting engagement with treatment and quality of life more broadly. There is now strong evidence for the effectiveness of cognition-focused treatments, such as cognitive remediation to improve clinical and functional outcomes for people with psychosis. However, engagement with treatment has been a long-standing issue in mental health care, including for people with psychosis, who often experience difficulties with motivation. While research on clinical effectiveness of cognition-focused treatment is growing, to date there has been little research focused on the implementation of such treatments and it is not clear how best to support uptake and engagement across diverse mental health settings. Implementation science is the study of methods and strategies to promote the adoption, application, and maintenance of evidence-based practices in routine care. To integrate cognition-focused treatments into routine practice, and improve engagement with treatment and the quality and effectiveness of care for people with psychosis, researchers need to embrace implementation science and research. This paper provides a succinct overview of the field of implementation science, current evidence for implementation of cognition-focused treatments for psychosis and practical guidance for using implementation science in clinical research. The future of psychosis research includes multidisciplinary teams of clinical researchers and implementation scientists, working together with providers and consumers to build the evidence that can improve the implementation of cognition-focused treatments.

A Comparison of the Relationship Between C-Reactive Protein Levels and Cognitive Functions in Patients with Schizophrenia, First-Episode Psychosis, and Healthy Controls.

There are several hypotheses on what causes schizophrenia, some of which include inflammatory responses. Additionally, it might be challenging to control and treat cognitive abnormalities, which represent the primary symptoms, and may be related to inflammation. This study aims to determine whether there is a relationship between C-reactive protein levels and cognitive abilities by assessing neuropsychological tests of drug-free patients with schizophrenia and first-episode psychosis. The patient group consisted of 36 patients with schizophrenia or "first-episode psychosis," while the control group comprised 31 healthy people. The control group consisted of healthy participants without any medical or psychiatric diseases. Structured Clinical Interview for DSM-5 axis I disorders was applied for diagnosis, while Wisconsin card sorting test, Stroop color and word test, trail making tests, Rey auditory verbal learning test, and digit span test were applied for cognitive assessment of both groups. Clinical characteristics of patients were evaluated by using the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Calgary Depression Scale for Schizophrenia. The patient group and healthy control group were evaluated in terms of inflammation levels. The C-reactive protein levels were measured, and their relationship with cognitive status was examined. The serum samples were analyzed by the immunoturbidimetric method in C-reactive protein C8000 Architect (Abbott, Ill, USA) to measure the C-reactive protein levels. C-reactive protein levels were found to be higher in the patient group (P = .003), while the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms scores were found to be positively correlated with C-reactive protein levels. Cognitive functions in the patient group were significantly lower compared to the healthy group. There was a statistically weak correlation between C-reactive protein and the number of word color reading errors in the Stroop test, which was associated with complex and frontal attention; however, no correlation was found with digit span test, Rey auditory verbal learning test, or Wisconsin card sorting test points. Elevated peripheral levels of C-reactive protein are associated with poorer cognitive function in patients with first-episode psychosis and schizophrenia, particularly, complex attention associated with the Stroop test. Inflammation may have an impact on cognitive impairment in psychosis.

Impairments in goal-directed action and reversal learning in a proportion of individuals with psychosis

Cognitive impairment in psychosis is one of the strongest predictors of functional decline. Problems with decision-making processes, such as goal-directed action and reversal learning, can reflect cortico-striatal dysfunction. The heterogenous symptoms and neurobiology observed in those with psychosis suggests that specific cognitive phenotypes may reflect differing causative mechanisms. As such, decision-making performance could identify subgroups of individuals with more severe cortico-striatal dysfunction and help to predict their functional decline. The present work evaluated the relationship between goal-directed action, reversal learning, and symptom profiles in those with psychosis. We assessed decision-making processes in healthy controls (N = 34) and those with persistent psychosis (N = 45), subclassifying subjects based on intact/impaired goal-directed action. Compared with healthy controls (<20%), a large proportion (58%) of those with persistent psychosis displayed impaired goal-directed action, predicting poor serial reversal learning performance. Computational approaches indicated that those with impaired goal-directed action had a decreased capacity to rapidly update their prior beliefs in the face of changing contingencies. Impaired decision-making also was associated with reduced levels of grandiosity and increased problems with abstract thinking. These findings suggest that prominent decision-making deficits, indicative of cortico-striatal dysfunction, are present in a large proportion of people with persistent psychosis. Moreover, these impairments would have significant functional implications in terms of planning and abstract thinking.

Digital technology for addressing cognitive impairment in recent-onset psychosis: A perspective

Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digital technology has the potential to address these limitations in order to improve cognitive and functional outcomes in recent-onset psychosis. Computer programs can be used for standardized, automated delivery of cognitive remediation training. Virtual reality provides the opportunity for learning and practicing cognitive skills in real-world scenarios within a virtual environment. Smartphone apps could be used for notification reminders for everyday tasks to compensate for cognitive difficulties. Internet-based technologies can offer psychoeducation and training materials for enhancing cognitive skills. Early findings indicate some forms of digital interventions for cognitive enhancement can be effective, with well-established evidence for human-supported computer-based cognitive remediation in recent-onset psychosis. Emerging evidence regarding virtual reality is favorable for improving social cognition. Overall, blending digital interventions with human support improves engagement and effectiveness. Despite the potential of digital interventions for enhancing cognition in recent-onset psychosis, few studies have been conducted to date. Implementation challenges affecting application of digital technologies for cognitive impairment in recent-onset psychosis are sustained engagement, clinical integration, and lack of quality in the commercial marketplace. Future opportunities lie in including motivational frameworks and behavioral change interventions, increasing service engagement in young people and lived experience involvement in digital intervention development.

Impact of polygenic risk for coronary artery disease and cardiovascular medication burden on cognitive impairment in psychotic disorders

BackgroundCognitive impairment is a core deficit across psychotic disorders, the causes and therapeutics of which remain unclear. Epidemiological observations have suggested associations between cognitive dysfunction in psychotic disorders and cardiovascular risk factors, but an underlying etiology has not been established. MethodsNeuropsychological performance using the Brief Assessment of Cognition in Schizophrenia (BACS) was assessed in 616 individuals of European ancestry (403 psychosis, 213 controls). Polygenic risk scores for coronary artery disease (PRSCAD) were quantified for each participant across 13 p-value thresholds (PT 0.5-5e−8). Cardiovascular and psychotropic medications were categorized for association analyses. Each PRSCAD was examined in relation to the BACS and the optimized PT was confirmed with five-fold cross-validation and independent validation. Functional enrichment analyses were used to identify biological mechanisms linked to PRSCAD-cognition associations. Multiple regression analyses examined PRSCAD under the optimal PT and medication burden in relation to the BACS composite and subtest scores. ResultsHigher PRSCAD was associated with lower BACS composite scores (p = 0.001) in the psychosis group, primarily driven by the Verbal Memory subtest (p < 0.001). Genes linked to multiple nervous system related processes and pathways were significantly enriched in PRSCAD. After controlling for PRSCAD, a greater number of cardiovascular medications was also correlated with worse BACS performance in patients with psychotic disorders (p = 0.029). ConclusionsHigher PRSCAD and taking more cardiovascular medications were both significantly associated with cognitive impairment in psychosis. These findings indicate that cardiovascular factors may increase the risk for cognitive dysfunction and related functional outcomes among individuals with psychotic disorders.

Thalamic Nuclei Volumes in Psychotic Disorders and in Youths With Psychosis Spectrum Symptoms.

Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided conflicting findings for structural deficits specific to these nuclei. The authors sought to characterize thalamic structural abnormalities in psychosis and a neurodevelopmental cohort, and to determine whether nuclear volumes were associated with cognitive function. Thalamic nuclei volumes were tested in a cross-sectional sample of 472 adults (293 with psychosis) and the Philadelphia Neurodevelopmental Cohort (PNC), consisting of 1,393 youths (398 with psychosis spectrum symptoms and 609 with other psychopathologies), using a recently developed, validated method for segmenting thalamic nuclei and complementary voxel-based morphometry. Cognitive function was measured with the Screen for Cognitive Impairment in Psychiatry in the psychosis cohort and the Penn Computerized Neurocognitive Battery in the PNC. The psychosis group had smaller pulvinar, mediodorsal, and, to a lesser extent, ventrolateral nuclei volumes compared with the healthy control group. Youths with psychosis spectrum symptoms also had smaller pulvinar volumes, compared with both typically developing youths and youths with other psychopathologies. Pulvinar volumes were positively correlated with general cognitive function. The study findings demonstrate that smaller thalamic association nuclei represent a neurodevelopmental abnormality associated with psychosis, risk for psychosis in youths, and cognitive impairment. Identifying specific thalamic nuclei abnormalities in psychosis has implications for early detection of psychosis risk and treatment of cognitive impairment in psychosis.

Motor abnormalities and cognitive impairment in first-episode psychosis patients, their unaffected siblings and healthy controls

Motor abnormalities (MAs) may be already evidenced long before the beginning of illness and are highly prevalent in psychosis. However, the extent to which the whole range of MAs are related to cognitive impairment in psychosis remains understudied.This study aimed to examine comparatively the relationships between the whole range of motor abnormalities and cognitive impairments in the first-episode of psychosis (FEP), their unaffected siblings and healthy control subjects.Fifty FEP patients, 21 of their healthy siblings and 24 age- and sex matched healthy controls were included. Motor assessment included catatonic, extrapyramidal and neurological soft signs (NSS) by means of standardized instruments. An exhaustive neuropsychological battery was also performed to extract the 7 cognitive dimensions of MATRICS initiative.Higher scores on NSS but not on extrapyramidal and catatonic signs showed significant associations with worse cognitive performance in the three study groups. However, the pattern of associations regarding specific cognitive functions was different among the three groups. Moreover, extrapyramidal signs showed significant associations with cognitive impairment only in FEP patients but not in their unaffected siblings and healthy controls. Catatonic signs did not show any significant association with cognitive functioning in the three study groups.These findings add evidence to the associations between motor abnormalities, particularly NSS and extrapyramidal signs, and cognitive impairment in first-episode psychosis patients. In addition, our results suggest that the specific pattern of associations between MAs and cognitive functioning is different in FEP patients from those of the unaffected siblings and healthy subjects.

Cognitive effects of adjunctive N-acetyl cysteine in psychosis.

Cognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder. A sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann-Whitney test was used to examine the differences between the NAC and placebo groups at the end point. Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027). NAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.

Using the cognitive assessment interview to screen cognitive impairment in psychosis.

Cognitive impairment in psychosis is closely related to functional outcome, so research into psychotic disorders is focusing most effort on treatments for improving cognition. New treatments must show not only an improvement on neuropsychological tests but also in co-primary measures of cognition. The cognitive assessment interview (CAI) is an interview-based measure of cognition which assesses the impact of cognitive deficits in patients' daily lives. Information obtained from patients and their relatives is integrated into a rater composite score. This study examines the validity of the CAI (adapted to Spanish, CAI-Sp) as a screening instrument for cognitive impairment, compared to an objective test of cognitive functioning. The psychometric properties of the CAI-Sp and its association with clinical dimensions are also explored. Eighty-one patients with a psychotic disorder and 38 healthy controls were assessed using the CAI-Sp and the screen for cognitive impairment in psychiatry (SCIP-S). Patients also underwent a clinical assessment. Poorer cognitive functioning as assessed with the CAI-Sp was associated to illness severity, specifically positive, negative and disorganised syndromes. Binary logistic regression showed that the CAI-Sp was able to detect cognitive impairment in patients, when considering CAI-Sp patient and informant information and CAI-Sp rater scores. The CAI-Sp was found to be a valid and reliable scale to assess cognitive functioning in the context of its impact on daily living. Given its ease and speed of application, the CAI-Sp could prove useful in clinical practice, though not a substitute of objective cognitive testing.

Free thyroxine levels are associated with cognitive abilities in subjects with early psychosis

IntroductionSubjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic–pituitary–thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis. MethodsWe studied 70 patients with a psychotic disorder (<3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder). ResultsIn patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis. ConclusionsOur study suggests that FT4 levels are associated with cognitive abilities (attention/vigilance and overall cognition) in individuals with early psychosis.

Familial liability to schizophrenia and mood disorders and cognitive impairment in psychosis

Schizophrenia and other psychoses are complex disorders with high rates of cognitive impairment and a considerable degree of genetic and environmental influence on its etiology. Whether cognitive impairment is related to dimensional scores of familial liability is still matter of debate. We conducted a cross-sectional study including 169 patients with psychotic disorders and 26 healthy controls. Attention, memory and executive functions were assessed, and familial loading scores for schizophrenia and mood disorders were calculated. The relationships between familial liability and neuropsychological performance were examined with Spearman׳s correlation coefficients. In addition, patients were classified into three groups by family loading tertiles, and comparisons were performed between the patients in the top and bottom tertiles. Low familial loading scores for schizophrenia showed a significant association with poor executive functioning and delayed visual memory. And these results were also achieved when the subset of psychotic patients in the two extreme tertiles of family loadings of schizophrenia and mood disorders were compared. Low familial liability to schizophrenia seems to be a contributing factor for the severity of cognitive impairment in patients with a broad putative schizophrenia spectrum diagnosis.

The Experience of Cognitive Impairment in People with Psychosis

Cognitive impairment has been widely studied in people with psychosis. However, research is lacking into the subjective experience of cognitive impairment, its impact and ways in which individuals cope. This study aimed to provide an account of the experience of cognitive impairment in people with a diagnosis of schizophrenia, including what difficulties people experience, how these difficulties are understood, how people respond to these difficulties and how they perceive others' views of these difficulties. A semi-structured interview was carried out with eight participants with a diagnosis of schizophrenia focusing on participants' experiences of difficulties with cognitive functioning. Interpretative phenomenological analysis was used to analyse interview transcripts. Experience of cognitive impairment was understood in terms of six master themes: impaired controlled thinking, physical sensations and impaired movement, explanations for the impairment and comparisons to the past, managing the impairment, how others see the impairment and anticipating the future. This study is the first rigorous qualitative study of the subjective experience of cognitive impairment in people with psychosis, and it provides greater context for empirical findings. The results have significant implications for clinical psychology, including education about cognitive difficulties and the importance of cognitive functioning to formulation. New areas for research include coping strategies in relation to functioning and future perspectives, ascertaining staff understanding of cognitive impairment, and reflective conversation style as an intervention for metacognitive difficulties. Key Practitioner Message Difficulties with cognitive functioning should be considered in clinical practitioners' formulations of clients' difficulties in the context of psychosis. Services should consider providing service user and carer education about cognitive impairment in psychosis. Staff may need further training in order to support people with psychosis who have difficulties with cognitive functioning.

Cognitive dysfunction among HIV positive and HIV negative patients with psychosis in Uganda.

BackgroundCognitive impairment is an established phenomenon in HIV infected individuals and patients that have psychosis. However there is need to establish the severity of the impairment if patients are co morbid with both conditions.AimTo compare cognitive function among HIV positive individuals and HIV negative individuals with psychosis.MethodsWe recruited patients with psychosis at two national referral hospitals. A standardized demographics questionnaire and psychiatric, physical, and laboratory assessments were conducted. Types of psychosis were diagnosed using the Mini International Neuropsychiatric Inventory-PLUS while cognitive functioning was determined using the Mini mental state examination (MMSE) and a neuropsychological test battery. Follow-up assessments on cognitive function and severity of psychiatric illness were performed at 3 and 6 months. Pairwise comparison and multivariable logistic regression analysis were used to determine the differences between the HIV positive and HIV negative individuals.ResultsThere were 156 HIV positive and 322 HIV negative participants. The mean age was 33 years for the HIV positive group and 29 years for the HIV negative group (p<0.001). The HIV positive individuals were almost three times (OR = 2.62 CI 95% 1.69–4.06) more likely to be cognitively impaired on the MMSE as well as the following cognitive tests:- WHO-UCLA Auditory Verbal Learning Test (OR 1.79, 95% CI 1.09–2.92), Verbal Fluency (OR 3.42, 95% CI 2.24–5.24), Color Trails 1 (OR 2.03, 95% CI 1.29–3.02) and Color Trails 2 (OR 3.50 95% 2.00–6.10) all p = 0.01. There was improvement in cognitive function at follow up; however the impairment remained higher for the HIV positive group (p<0.001).ConclusionCognitive impairment in psychosis was worsened by HIV infection. Care plans to minimize the effect of this impairment should be structured for the management of individuals with HIV and psychosis.

Association of symptoms and executive function in schizophrenia and bipolar disorder

The extent to which cognitive impairment in psychosis is related to the particular disorder or the pattern of symptoms is unclear. We examined executive function in two groups of schizophrenia patients with predominant symptoms of disorganisation ( n=15) and psychomotor poverty ( n=15), respectively, two groups of bipolar I disorder patients with predominant symptoms of mania ( n=15) and depression ( n=15), respectively, and 30 healthy controls. We predicted that the pattern of symptoms (‘excess’ [disorganisation/mania] or ‘deficiency’ [negative symptoms/depression]) would be more related to executive ability than the underlying disorder. The patient groups showed partially overlapping executive dysfunctions relative to the control group. There were no significant differences between groups with ‘excess’ symptoms (schizophrenia patients with thought disorder and bipolar patients with mania), or between groups with ‘deficiency’ symptoms (schizophrenia patients with negative symptoms and bipolar patients with depression). In contrast, differences were noted between groups with the same diagnosis: Schizophrenia patients with disorganisation were less accurate in semantic verbal fluency than those with negative symptoms; and bipolar patients with mania tended to be faster, but less accurate, in sentence completion than those with depression. A statistical comparison of the associations of ‘diagnosis’ and the ‘excess-deficiency’ dimension with executive function revealed a trend for a greater association of the latter with two measures of performance accuracy. Executive dysfunction in patients with psychotic disorders may be more related to their symptom profile than their diagnosis.