Cognitive deficits in recent-onset and chronic schizophrenia

ObjectiveThis study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients.MethodsThis was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics−Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years’ duration of the illness.ResultsAmong the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group.ConclusionHigh rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent-onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

BackgroundEarly-stage visual processing deficits are evident in chronic schizophrenia. Consistent with a cascade model of information processing, whereby early perceptual processes have downstream effects on higher-order cognition, impaired visual processing is associated with deficits in social cognition in this clinical population. However, the nature of this relationship in the early phase of illness is unknown. Here, we present data from a study of early visual processing and social cognitive performance in recent-onset schizophrenia (ROSz).MethodThirty-two people with ROSz and 20 healthy controls (HC) completed a visual backward masking task using stimuli of real world objects (Object Masking) to assess early-stage (i.e., 0–125 ms post-stimulus onset) visual processing. Subjects also completed two tasks of social cognition, one assessing relatively low-level processes of emotion identification (Emotion Biological Motion, EmoBio), and another assessing more complex, higher-order theory of mind abilities (The Awareness of Social Inference Test, TASIT). Group differences were tested with repeated measures ANOVAs and t-tests. Bivariate correlations and linear regressions tested the strength of associations between early-stage visual processing and social cognitive performance in ROSz.ResultsFor Object Masking, the mask interfered with object identification over a longer interval for ROSz than for HC [F (3.19, 159.35) = 8.51, p < 0.001]. ROSz were less accurate on the EmoBio task [t (50) = −3.36, p = 0.001] and on the TASIT compared to HC [F (1, 50) = 38.37, p < 0.001]. For the TASIT ROSz were disproportionately impaired on items assessing sarcasm detection [F (1, 50) = 4.30, p = 0.04]. In ROSz, better Object Masking performance was associated with better social cognitive performance [rEmoBio = 0.45, p < 0.01; rTASIT = 0.41, p < 0.02]. Regression analyses did not provide significant support for low-level social cognition mediating the relationship between visual processing and high-level social cognition.ConclusionEarly-stage visual processing, low-level social cognition, and high-level social cognition were all significantly impaired in ROSz. Early-stage visual processing was associated with performance on the social cognitive tasks in ROSz, consistent with a cascade model of information processing. However, significant cascading effects within social cognition were not supported. These data suggest that interventions directed at early visual processing may yield downstream effects on social cognitive processes.

Association between mismatch negativity and global functioning is specific to duration deviance in early stages of psychosis

There is abundant evidence that neurocognitive deficits are present in schizophrenic patients (Aylward et al.  ). A recent meta-analytical review of  neurocognitive test variables concluded that schizophrenia is characterized by a broadly based, moderately severe (d =  .  ) cognitive impairment, with varying degrees of deficit in all domains (Heinrichs & Zakzanis  ). In comparison with learning disability these deficits are mild, with around  % of patients scoring in the deficit range on most tests of cognitive function (Green  ). This review will summarize some of the key findings regarding the relationship of cognitive deficits to the aetiology of schizophrenia.

The aim of this study was to see whether and how cognition deficit predicts quality of life impairments in schizophrenia patients. The Computerized Cambridge Automated Neuropsychological Test Battery, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Quality of Life Scale (QLS) were used to assess 62 patients with chronic schizophrenia. Step-wise multiple regression analysis was used in order to determine cognitive variables that would predict the scores of each Q-LES-Q and QLS domain scores. Regression analysis revealed a significant association of the cognitive deficits with both general and domain-specific quality of life impairment measured with Q-LES-Q and QLS. Deficits in executive functions, visual sustained attention, memory and motor skills have been found to be valid predictors both before and after controlling for the severity of symptoms, emotional distress, side effects, age, education, and illness duration. This study suggests that deficits in executive functioning, attention, memory and motor skills substantially contributes to predicting impairments across a wide range of HRQL domains, and, consequently, to quality of life appraisal in schizophrenia. Cognitive predictors cannot be attributed to illness-related and background variables. It can be concluded that, when aiming at the improvement of quality of life in schizophrenia patients, cognitive functioning should be targeted.

Studying Heart Arrhythmias in Relation to Psychosis (SHARP). Increased Prevalence of ECG Suspect for Brugada Syndrome in Recent Onset Schizophrenia.

Cognitive Impairment in Dialysis Patients: Focus on the Blood Vessels?

Accumulating studies have revealed gender differences in many aspects of schizophrenia (SZ), including obesity and cognitive function. The relationship between obesity and cognitive impairment in SZ has been studied before; however, the results are inconsistent. This study was designed to examine the sex differences in the relationship between body mass index (BMI) and cognitive deficits in Chinese patients with chronic SZ, which have not been investigated yet. 176 chronic patients with SZ (male/female = 108/68) and 200 controls (male/female = 120/80) were enrolled to compare the sex differences in cognitive functions measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), BMI, and their associations. The clinical symptoms were evaluated using the positive and negative syndrome scales (PANSS). Our results showed that male patients had lower BMI and more negative symptoms but fewer positive symptoms than female patients (all p < 0.05). However, there was no significant sex difference in RBANS scores. In male patients, BMI was correlated with age of onset, PANSS general psychopathology, total score, negative symptom, together with RBANS language, visuospatial/construction, and attention. Further regression analysis showed that in male patients, BMI was significantly associated with RBANS language, PANSS general psychopathology, PANSS total score, and age of onset, with adjusted R2 = 0.22. These findings revealed significant sex differences in BMI, cognitive dysfunctions and their association in SZ. Nonetheless, these results should only be considered as preliminary because of the cross-sectional design, which will deserve further replication in first-episode patients using a prospective longitudinal design.

Clinical and biological complexity is the rule rather than the exception in geriatric psychiatric syndromes. Typically, geriatric psychopathology develops in the context of medical and neurological disorders. Under these circumstances, ascertainment of symptoms and signs is difficult. Moreover, behavioral abnormalities, cognitive deficits, and physical symptoms and signs are often contributed by more than one psychiatric, neurological, or medical condition. Finally, symptoms change over time as various coexisting disease processes progress or subside, further complicating clinical assessment and diagnosis. Complexity has been viewed as an obstacle to medical research, which by necessity depends on reduction. Biological and psychosocial hypotheses are nothing but logical reductions, designed to permit understanding of a small part of a larger problem. Experimental design is an operational reduction intended at giving the best chance for hypothesis testing. Such reduction processes become complicated by the clinical intricacies of geriatric psychiatry syndromes. Despite the logical and experimental challenges posed by geriatric syndromes, their complexity has begun to provide meaningful clinical and biological information. Studying depression in Alzheimer’s disease patients exemplifies how comorbid geriatric syndromes can help address clinical and biological questions. In the study by Zubenko et al. in this issue [May 2003], the high prevalence of depression in patients with probable Alzheimer’s disease was confirmed. The study also observed that the depressive syndrome of Alzheimer’s patients is of mild severity and characterized by indecisiveness and diminished ability to concentrate but with limited depressive ideation and sleep disturbances. This symptom profile is difficult to distinguish from an uncomplicated dementia syndrome, thereby contributing to the underrecognition of depression. The increased frequency of psychotic symptoms in depressed Alzheimer’s disease patients further complicates ascertainment of depression. The difficulty in diagnosing depression is evidenced by the wide differences in depression prevalence estimates among patients with Alzheimer’s disease. Improving the methods of ascertainment (1) and treatment of depression in Alzheimer’s patients is critical, since depression contributes to excess disability, personal suffering, family disruption, and premature institutionalization. In addition to highlighting an important clinical problem, the comorbidity of depression and dementia has served as the stimulus for answering both clinical and biological questions. The early concept of “pseudodementia” was based on the assumption that the biological abnormalities of depression were the unitary cause of reversible Clinical and Biological Interactions in Affective and Cognitive Geriatric Syndromes George S. Alexopoulos, M.D.

935 – Cerebellar motor learning deficits in patients with recent-onset schizophrenia

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

BackgroundRepeated cognitive testing can boost performance due to practice effects (PEs). Follow‐up scores are rarely adjusted for PEs, but such correction can be highly important as it has been shown to result in earlier detection of MCI and increased validity based on concordance with Alzheimer's biomarkers. However, it remains unclear to what extent PEs persist across multiple follow‐ups and long durations, which are further complicated by normative age‐related decline. We examined PEs across 17 years from midlife to old age in a nonclinical sample.MethodMen (N = 1,608) in the longitudinal Vietnam Era Twin Study of Aging (VETSA) completed neuropsychological batteries over 4 waves: wave 1(N = 1,290, mean age=56); wave 2, mean ages=62); wave 3 (mean age=68); wave 4 (mean age=73). Waves 2 and 3 also included age‐matched attrition replacements. By comparing returnees’ performance to replacements being assessed for the first time, we estimated PEs for 30 tests at each wave using generalized estimating equations, accounting for normative age effects and differential patterns of missingness. We calculated unadjusted and PE‐adjusted cognitive scores (episodic memory, executive function, fluency, processing speed, visual memory, and visuospatial). At each wave we compared MCI prevalence based on unadjusted versus PE‐adjusted scores.ResultAmong returnees completing all 4 assessments, we found significant PEs for 11 tests at wave 2, 8 tests at wave 3, and 5 tests at wave 4. PEs were most apparent among episodic and visual memory tests. PE‐adjusted cognitive factor scores were significantly lower than unadjusted factor scores at all follow‐ups for all domains except fluency. MCI prevalence increased up to 20% after PE adjustment (from 14% to 18% at wave 4), indicating earlier detection.ConclusionPEs persist across multiple assessments and decades, even with long testing intervals. Importantly, even very small PEs can shift scores below the impairment threshold, resulting in earlier detection and diagnosis of MCI. Additionally, we previously showed that PE‐adjusted MCI diagnosis increases accuracy based on biomarker concordance and would dramatically reduce costs and length of clinical trials by reducing necessary sample size and increasing power. These results underscore the importance of accounting for PEs in longitudinal studies.

Subtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are characteristic phenomena in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia found NSS to be associated with cortical, thalamic and cerebellar changes. Since these studies mainly focused on first-episode or recent onset schizophrenia, the cerebral correlates of NSS in chronic schizophrenia remained rather unclear. 49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter (GM) by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12/CAT12 analyses. As expected, NSS in patients were significantly (p≤0.001) elevated in contrast to healthy controls, a finding, which not only applied to NSS total score, but also to the respective subscales “motor coordination”, “sensory integration”, “complex motor tasks”, “right/left and spatial orientation” and “hard signs”. Within the patient group NSS total scores were significantly correlated to reduced GM in right lingual gyrus, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). Respective negative associations could also be revealed for the subscales “motor coordination”, “complex motor tasks” and “right/left and spatial orientation”. These findings remained significant after FWE-correction for multiple comparisons and were confirmed when years of education, chlorpromazine-equivalents or variables indicating the severity of psychopathology were introduced as additional covariates. According to our results lingual, parahippocampal, superior temporal, inferior and middle frontal gyri, thalamus and cerebellum have to be considered as important sites of NSS in chronic schizophrenia. That these findings only applied for patients but not healthy controls may indicate a different pathogenesis of NSS.

This large nationwide study describes the prevalence and predictors of long-term antipsychotic polypharmacy among patients with schizophrenia. A register-based longitudinal study of all people in Finland, who had at least one hospitalization due to schizophrenia during the years 2000-2007 and who were alive on March 1, 2007. Entry to the cohort was defined from the first hospitalization for schizophrenia during the years 2000-2007, and the date of assessment of antipsychotic polypharmacy was March 1, 2007. We studied separately chronic (N = 8,037) and recent onset (N = 8,046) schizophrenia patients. Antipsychotic polypharmacy was defined as overlapping of two or more filled prescriptions of antipsychotics for over 60 days. In a total 16,083 patients with schizophrenia the prevalence of antipsychotic polypharmacy was 46.2 % (N = 7,436, mean age 47.5 years, male 55 %). The longer the duration of schizophrenia, the more common the antipsychotic polypharmacy. Long index hospitalization and being male significantly associated with antipsychotic polypharmacy among all schizophrenia patients. Especially, in chronic schizophrenia patients, the previous use of benzodiazepine like agents was associated with antipsychotic polypharmacy, but the use of antidepressants associated with less frequent antipsychotic polypharmacy. Antipsychotic polypharmacy was widely prevalent among patients with schizophrenia and it was associated with long hospitalizations and long duration of illness. Benzodiazepine use was associated with increased risk and antidepressant use with decreased risk of antipsychotic polypharmacy when the effect of other clinical and socioeconomic factors was adjusted. Research is needed of risks and benefits of antipsychotic polypharmacy and augmentation of antipsychotic with other psychoactive drugs.

Recovery From Schizophrenia: A Concept in Search of Research